Embryology - User contributions [en-gb]

User:Z3463514

2015-10-30T02:20:17Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

Lab 10 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:03, 16 October 2015 (AEDT)

Lab 11 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:06, 23 October 2015 (AEDT)

Lab 12 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:20, 30 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 7 Assessment==
 1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical. 

<pubmed>25315894</pubmed>

The pituitary gland is a major endocrine organ located at the base of the brain, it is responsible in controlling growth and development and the functioning of the other endocrine glands. The purpose of this research article was to investigate the mechanism underlying the pituitary defects. This was carried out by using different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. OTX2 is a homeo-domain transcription factor that is required for normal head development in mouse and human. Affected individuals exhibit a spectrum of features that range from developmental defects in eye or pituitary development. Mice that expresses Otx2 deficiency in early head development and pituitary oran ectoderm exhibit craniofacial defects and pituitary gland malformation at birth.

The research demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe, and extrinsic effects on anterior pituitary growth. The findings of this research suggest that mechanisms that underlie the diminished hormone secretion by the pituitary gland in patients with Otx2 mutations. The variable ocular, cranio-facial and pituitary defects that arose in Otx2 expression are consistent with the dosage sensitivity for Otx2 in early head development.

 2. Identify the embryonic layers and tissues that contribute to the developing teeth. 

Teeth development is also known as "Odontogenesis", this process commences in week 6 of embryonic development. It involves the ectoderm of the first pharyngeal arch and neural crest, ectomesenchyme.

Embryonic layers and tissues that contribute to the developing teeth:

1. Ameoblast - Epithelial cells that are derived from the oral epithelium of ectoderm and produces teeth enamel. Ameloblasts are the result from preameloblast differentiation which originate from inner enamel epithelium.

2. Odontoblasts - Mesenchymal cells which are derived from the neural crest; depending on their enamel epithelium activity they will differentiate differently. These cells produce predentin which calcifies to dentin which is found beneath the enamel in the crown region and under the cementum in within the root.

3. Periodontal ligament - It provides attachment of the teeth to the alveolar bone of the maxillae and the mandible. The periodontal ligament is composed of fibroblasts, epithelial cells, undifferentiated mesenchymal cells, bone, cementum cells and bundles of collagen fibres.

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

==Lab 9 Assessment - Permalink==

Retinal Pigment Epithelium

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2841&lon=5935&layers=B Retinal Pigment Epithelium]

Retinal pigment epithelium (RPE) cells are generated from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye. RPE are cuboidal cells with multiple villi on its apical side which are in direct contact with the outer segments of the photoreceptor cells. Its lateral sides are joined together by tight junctions, adherens and gap junctions. The basal side of the retinal pigment epithelium is in contact with the underlying basal membrane which is also known as the Bruch's membrane. The permalink shows that the sensory retina and pigmented epithelium are separated by a space called the optic ventricle. In the adult the optic ventricle will no longer be present and the 2 layers would be closely associated to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

2015 Group Project 4

2015-10-23T09:20:06Z

Z3463514: /* Seminiferous Tubules */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref name=PMID14617369><pubmed>14617369</pubmed></ref> . Spermatozoa also consists of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes <ref name=PMID14617369><pubmed>14617369</pubmed></ref>]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa.<ref name=PMID14617369><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

===Seminiferous Tubules===

Seminiferous tubules special tubular structures in the testis that produce and release sperm continuously throughout the male life cycle. <ref><pubmed> 5582405</pubmed></ref> The structure of the seminiferous tubules are complex stratified epithelium which is in invested by a capsule (tunica propria) of fibroelastic tissue and flattened fibroblasts. The spermatozoa within the tubules are not motile, it is believed that they are transported to efferent ducts by the continuous pushing motion provided by the production and release of new spermatozoa. It is also transported via the secretion of fluid from the tubules to the proximal region of the epididymal duct. <ref><pubmed> 26391090 </pubmed></ref>
Problems in the seminiferous tubules can arise due to a blockage caused by ejaculatory duct obstruction. This can ultimately result in obstructive azoospermia, as described in "Male Infertility Disorders".

==Male infertility disorders==

Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may affect a different aspect of the male's sperm including sperm count, morphology and motility rates.
A fertile male is suggested to have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail.

Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly.

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref>
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility <ref name=PMID21243017><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|400px|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.<ref><pubmed> 26246871</pubmed></ref>]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|400px|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.<ref><pubmed> 26157295</pubmed></ref>]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.<ref><pubmed>26157295</pubmed></ref>]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia <ref name=PMID14617369><pubmed>14617369</pubmed></ref>]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref name=PMID21243017><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref name=PMID16903932><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref name=PMID16903932><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility.<ref name=PMID21243017><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
{|
|-
| [[File:Color Doppler ultrasonography of varicocele.jpeg|400px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position. <ref name=PMID25685302><pubmed>25685302</pubmed></ref>]]
| High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination <ref name=PMID25685302><pubmed>25685302</pubmed></ref>. It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour.<ref name=PMID16903932><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis <ref name=PMID25685302><pubmed>25685302</pubmed></ref>.
|}

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|400px|thumb|right|Development of Gonadotropin Preparations <ref><pubmed>24714837</pubmed></ref>]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>.

The following are a few common antioxidants that have been proven to treat oxidative stress, and hence improves male fertility.

=====1. Carotenoids=====
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>.
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments.
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>.
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|400px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility <ref name=PMID24675655><pubmed>24675655</pubmed></ref>]]

Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below.

======Lycopenes======
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon.
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>.
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>.
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage.
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

======Astaxanthin======
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine.
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels.

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|400px|right|Model of the Activities of Cerium Dioxide Nanoparticles <ref name=PMID26097523><pubmed>26097523</pubmed></ref>]]

======2. Cerium dioxide nanoparticles (CNPs)======
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>.
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>.
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

======3. Vitamin E======
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds.
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

======4. Vitamin C======
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower.
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female.
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref>
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure <ref><pubmed>18996517</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=ENrx7o_z9Ng</html5media>

IUI Treatment Procedure <ref>Indira IVF. (2014, July 27) What is IUI treatment for Pregnancy. Retrieved from https://www.youtube.com/watch?v=ENrx7o_z9Ng</ref>

====In Vitro Fertilisation (IVF)====

Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles <ref name=PMID26473112><pubmed>26473112</pubmed></ref>. Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.

Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia <ref name=PMID26473112><pubmed>26473112</pubmed></ref>.
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins.

The next step is for the oocytes and semen to undergo co-incubation <ref><pubmed>26460690</pubmed></ref>. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation.

The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues.
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. One of the most relevant clinical implications of ICSI is the ability to produce a viable embryo from an immature oocyte and a single spermatozoon injection; particularly due to the high proportion (15-20%) of oocytes retrieved when immature. <ref name=PMID26473112><pubmed>26473112</pubmed></ref>
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile <ref><pubmed>26473111</pubmed></ref>.
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes). The following shows the simplified steps of performing ICSI, and is also outlined in the video provided.
*The female is administered various hormones to stimulate ovulation to release an oocyte, then the oocyte or several oocytes are removed and stored.
*Simultaneously, the males ejaculate is also collected and only a single spermatozoa may be required for fertilisation.
*Fertilisation is acheived by the directly injecting a spermatozoon into one stored oocyte using a fine needle.
*After 2 or 3 days, if fertilisation has successfully occured, the embryo will be transferred into the female's uterus to allow for implantation, and hopefully lead to pregnancy <ref name=PMID26473112><pubmed>26473112</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media>

ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref>

===Current Research and Animal Models===

The research involving male infertility most recently, is surrounding more innovative techniques to identify new and different targets to treat and diagnose the condition. A study performed in September, 2015 investigated the efficacy of using sperm chromatin structure assays to determine fertility in Nigerian men <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. A total of 404 men consisting of fertile and unexplained infertile men underwent both semen analysis and sperm chromatin structure assays. Through the measurement of DNA fragmentation index, there was a more significant difference between infertile and fertile men when using sperm chromatin structure assaying <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. Therefore this new diagnostic tool may be more accurate in determining the fertility potential of males. Not only does this allow for a more predictive indicator, but it may also lead future research to use modify these technologies and perhaps find the specific molecular and cellular pathways that are affected in each individual male.

Additionally, animal models have been used extensively and have resulted in major findings in treatments and pathways of male infertility. The following are examples of current research that have used animal models to make way for unique findings that have implications on future studies.

====Rat Model====
A study performed in August, 2015 investigated the potential for bone marrow mesenchymal stem cells to restore the internal reproductive testis in male rats with azoospermia. A total of 22 rat models underwent transplantation of rat bone marrow mesenchymal stem cells into the seminiferous tubules of the testis <ref name=PMID26442294><pubmed>26442294</pubmed></ref>. Observations were made to establish differences in the structure and composition of the cells in the seminiferous tubules. Results showed that these specific stem cells are able to differentiate into germ cells and have the potential to repair seminiferous tubules that are damaged in azoospermic rats <ref name=PMID26442294><pubmed>26442294</pubmed></ref>.

====Primate Model====

Similar to the rat study, a population of monkeys known as rhesus macaques was used to test the effects of spermatogonial stem cells on infertility. These cells are fundamental to spermatogenesis, thus have a role in maintaining fertility of the male <ref><pubmed>17141059</pubmed></ref>. This particular research involved transplanting spermatogonial stem cells into the seminiferous tubules in the testes of 18 adult, and 5 prepubertal and infertile rhesus macaques, by ultrasound-guided injections <ref name=PMID23122294><pubmed>23122294</pubmed></ref>. There were significant improvements in adult test subjects as the level of spermatogenesis were of normal levels, meaning sperm count increased to normal levels. Through the use of large primate models, the potential for spermatogonial stem cells to rejuvenate spermatogenesis in seminiferous tubules has been established <ref name=PMID23122294><pubmed>23122294</pubmed></ref>. Future research regarding the functioning of sperm produced by spermatogonial stem cells will make ground breaking implications on fertility clinics and current ARTs that are available to infertile couples.

==Glossary==

ARTs - Assisted Reproductive Technologies

Aetiological factors - causative agents

Aneuploidy - the presence of an abnormal number of chromosomes in a cell

Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production

Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonads

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism

Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome

LH - Luteinizing hormone

Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS

Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching

Quenching - the deactivation of reactive oxygen forms

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

Spermatogenesis - the production of development of new sperm

Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref>

TCM - Traditional Chinese medicine

Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref>

TMS - Total Motile Sperm

TURED - Transurethral resection of ejaculatory ducts

Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood

==References==

<references/>

2015 Group Project 4

2015-10-23T07:14:26Z

Z3463514: /* Seminiferous Tubules */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref name=PMID14617369><pubmed>14617369</pubmed></ref> . Spermatozoa also consists of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes <ref name=PMID14617369><pubmed>14617369</pubmed></ref>]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa.<ref name=PMID14617369><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

===Seminiferous Tubules===

Seminiferous tubules special tubular structures in the testis that produce and release sperm continuously throughout the male life cycle. <ref><pubmed> 5582405</pubmed></ref> The structure of the seminiferous tubules are complex stratified epithelium which is in invested by a capsule (tunica propria) of fibroelastic tissue and flattened fibroblasts. The spermatozoa within the tubules are not motile, it is believed that they are transported to efferent ducts by the continuous pushing motion provided by the production and release of new spermatozoa. It is also transported via the secretion of fluid from the tubules to the proximal region of the epididymal duct. <ref><pubmed> 26391090 </pubmed></ref>

==Male infertility disorders==

Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may affect a different aspect of the male's sperm including sperm count, morphology and motility rates.
A fertile male is suggested to have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail.

Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly.

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref>
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|400px|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.<ref><pubmed> 26246871</pubmed></ref>]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|400px|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.<ref><pubmed> 26157295</pubmed></ref>]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.<ref><pubmed>26157295</pubmed></ref>]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia <ref name=PMID14617369><pubmed>14617369</pubmed></ref>]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
{|
|-
| [[File:Color Doppler ultrasonography of varicocele.jpeg|400px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position. <ref name=PMID25685302><pubmed>25685302</pubmed></ref>]]
| High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination <ref name=PMID25685302><pubmed>25685302</pubmed></ref>. It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis <ref name=PMID25685302><pubmed>25685302</pubmed></ref>.
|}

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|400px|thumb|right|Development of Gonadotropin Preparations <ref><pubmed>24714837</pubmed></ref>]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>.

The following are a few common antioxidants that have been proven to treat oxidative stress, and hence improves male fertility.

=====1. Carotenoids=====
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>.
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments.
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>.
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|400px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility <ref name=PMID24675655><pubmed>24675655</pubmed></ref>]]

Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below.

======Lycopenes======
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon.
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>.
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>.
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage.
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

======Astaxanthin======
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine.
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels.

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|400px|right|Model of the Activities of Cerium Dioxide Nanoparticles <ref name=PMID26097523><pubmed>26097523</pubmed></ref>]]

======2. Cerium dioxide nanoparticles (CNPs)======
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>.
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>.
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

======3. Vitamin E======
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds.
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

======4. Vitamin C======
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower.
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female.
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref>
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure <ref><pubmed>18996517</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=ENrx7o_z9Ng</html5media>

IUI Treatment Procedure <ref>Indira IVF. (2014, July 27) What is IUI treatment for Pregnancy. Retrieved from https://www.youtube.com/watch?v=ENrx7o_z9Ng</ref>

====In Vitro Fertilisation (IVF)====

Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles <ref =namePMID26473112><pubmed>26473112</pubmed></ref>. Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.

Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia <ref =namePMID26473112><pubmed>26473112</pubmed></ref>.
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins.

The next step is for the oocytes and semen to undergo co-incubation <ref><pubmed>26460690</pubmed></ref>. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation.

The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues.
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. One of the most relevant clinical implications of ICSI is the ability to produce a viable embryo from an immature oocyte and a single spermatozoon injection; particularly due to the high proportion (15-20%) of oocytes retrieved when immature. <ref name=PMID26473112><pubmed>26473112</pubmed></ref>
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile <ref><pubmed>26473111</pubmed></ref>.
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes). The following shows the simplified steps of performing ICSI, and is also outlined in the video provided.
*The female is administered various hormones to stimulate ovulation to release an oocyte, then the oocyte or several oocytes are removed and stored.
*Simultaneously, the males ejaculate is also collected and only a single spermatozoa may be required for fertilisation.
*Fertilisation is acheived by the directly injecting a spermatozoon into one stored oocyte using a fine needle.
*After 2 or 3 days, if fertilisation has successfully occured, the embryo will be transferred into the female's uterus to allow for implantation, and hopefully lead to pregnancy <ref name=PMID26473112><pubmed>26473112</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media>

ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref>

===Current Research===

The research involving male infertility most recently, is surrounding more innovative techniques to identify new and different targets to treat and diagnose the condition. A study performed in September, 2015 investigated the efficacy of using sperm chromatin structure assays to determine fertility in Nigerian men <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. A total of 404 men consisting of fertile and unexplained infertile men underwent both semen analysis and sperm chromatin structure assays. Through the measurement of DNA fragmentation index, there was a more significant difference between infertile and fertile men when using sperm chromatin structure assaying <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. Therefore this new diagnostic tool may be more accurate in determining the fertility potential of males. Not only does this allow for a more predictive indicator, but it may also lead future research to use modify these technologies and perhaps find the specific molecular and cellular pathways that are affected in each individual male.

Additionally, animal models have been used extensively and have resulted in major findings in treatments and pathways of male infertility. The following are examples of current research that have used animal models to make way for unique findings that have implications on future studies.

====Rat Model====
A study performed in August, 2015 investigated the potential for bone marrow mesenchymal stem cells to restore the internal reproductive testis in male rats with azoospermia. A total of 22 rat models underwent transplantation of rat bone marrow mesenchymal stem cells into the seminiferous tubules of the testis <ref name=PMID26442294><pubmed>26442294</pubmed></ref>. Observations were made to establish differences in the structure and composition of the cells in the seminiferous tubules. Results showed that these specific stem cells are able to differentiate into germ cells and have the potential to repair seminiferous tubules that are damaged in azoospermic rats <ref name=PMID26442294><pubmed>26442294</pubmed></ref>.

====Rhesus Macaques Model====

==Glossary==

ARTs - Assisted Reproductive Technologies

Aetiological factors - causative agents

Aneuploidy - the presence of an abnormal number of chromosomes in a cell

Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production

Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonads

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism

Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome

LH - Luteinizing hormone

Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS

Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching

Quenching - the deactivation of reactive oxygen forms

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

Spermatogenesis - the production of development of new sperm

Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref>

TCM - Traditional Chinese medicine

Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref>

TMS - Total Motile Sperm

TURED - Transurethral resection of ejaculatory ducts

Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood

==References==

<references/>

2015 Group Project 4

2015-10-23T07:02:40Z

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{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref name=PMID14617369><pubmed>14617369</pubmed></ref> . Spermatozoa also consists of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes <ref name=PMID14617369><pubmed>14617369</pubmed></ref>]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa.<ref name=PMID14617369><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

===Seminiferous Tubules===

Seminiferous tubules special tubular structures in the testis that produce and release sperm continuously throughout the male life cycle. <ref><pubmed> 5582405</pubmed></ref> The structure of the seminiferous tubules are complex stratified epithelium which is in invested by a capsule (tunica propria) of fibroelastic tissue and flattened fibroblasts. The spermatozoa within the tubules are not motile, it is believed that they are transported to efferent ducts by the continuous pushing motion provided by the production and release of new spermatozoa, or by the secretion of fluid from the tubules to the proximal region of the epididymal duct. <ref><pubmed> 26391090 </pubmed></ref>

==Male infertility disorders==

Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may affect a different aspect of the male's sperm including sperm count, morphology and motility rates.
A fertile male is suggested to have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail.

Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly.

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref>
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|400px|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.<ref><pubmed> 26246871</pubmed></ref>]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|400px|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.<ref><pubmed> 26157295</pubmed></ref>]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.<ref><pubmed>26157295</pubmed></ref>]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia <ref name=PMID14617369><pubmed>14617369</pubmed></ref>]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
{|
|-
| [[File:Color Doppler ultrasonography of varicocele.jpeg|400px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position. <ref name=PMID25685302><pubmed>25685302</pubmed></ref>]]
| High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination <ref name=PMID25685302><pubmed>25685302</pubmed></ref>. It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis <ref name=PMID25685302><pubmed>25685302</pubmed></ref>.
|}

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|400px|thumb|right|Development of Gonadotropin Preparations <ref><pubmed>24714837</pubmed></ref>]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>.

The following are a few common antioxidants that have been proven to treat oxidative stress, and hence improves male fertility.

=====1. Carotenoids=====
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>.
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments.
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>.
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|400px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility <ref name=PMID24675655><pubmed>24675655</pubmed></ref>]]

Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below.

======Lycopenes======
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon.
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>.
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>.
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage.
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

======Astaxanthin======
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine.
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels.

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|400px|right|Model of the Activities of Cerium Dioxide Nanoparticles <ref name=PMID26097523><pubmed>26097523</pubmed></ref>]]

======2. Cerium dioxide nanoparticles (CNPs)======
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>.
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>.
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

======3. Vitamin E======
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds.
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

======4. Vitamin C======
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower.
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female.
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref>
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure <ref><pubmed>18996517</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=ENrx7o_z9Ng</html5media>

IUI Treatment Procedure <ref>Indira IVF. (2014, July 27) What is IUI treatment for Pregnancy. Retrieved from https://www.youtube.com/watch?v=ENrx7o_z9Ng</ref>

====In Vitro Fertilisation (IVF)====

Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles <ref =namePMID26473112><pubmed>26473112</pubmed></ref>. Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.

Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia <ref =namePMID26473112><pubmed>26473112</pubmed></ref>.
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins.

The next step is for the oocytes and semen to undergo co-incubation <ref><pubmed>26460690</pubmed></ref>. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation.

The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues.
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. One of the most relevant clinical implications of ICSI is the ability to produce a viable embryo from an immature oocyte and a single spermatozoon injection; particularly due to the high proportion (15-20%) of oocytes retrieved when immature. <ref name=PMID26473112><pubmed>26473112</pubmed></ref>
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile <ref><pubmed>26473111</pubmed></ref>.
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes). The following shows the simplified steps of performing ICSI, and is also outlined in the video provided.
*The female is administered various hormones to stimulate ovulation to release an oocyte, then the oocyte or several oocytes are removed and stored.
*Simultaneously, the males ejaculate is also collected and only a single spermatozoa may be required for fertilisation.
*Fertilisation is acheived by the directly injecting a spermatozoon into one stored oocyte using a fine needle.
*After 2 or 3 days, if fertilisation has successfully occured, the embryo will be transferred into the female's uterus to allow for implantation, and hopefully lead to pregnancy <ref name=PMID26473112><pubmed>26473112</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media>

ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref>

===Current Research===

The research involving male infertility most recently, is surrounding more innovative techniques to identify new and different targets to treat and diagnose the condition. A study performed in September, 2015 investigated the efficacy of using sperm chromatin structure assays to determine fertility in Nigerian men <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. A total of 404 men consisting of fertile and unexplained infertile men underwent both semen analysis and sperm chromatin structure assays. Through the measurement of DNA fragmentation index, there was a more significant difference between infertile and fertile men when using sperm chromatin structure assaying <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. Therefore this new diagnostic tool may be more accurate in determining the fertility potential of males. Not only does this allow for a more predictive indicator, but it may also lead future research to use modify these technologies and perhaps find the specific molecular and cellular pathways that are affected in each individual male.

Additionally, animal models have been used extensively and have resulted in major findings in treatments and pathways of male infertility. The following are examples of current research that have used animal models to make way for unique findings that have implications on future studies.

====Rat Model====
A study performed in August, 2015 investigated the potential for bone marrow mesenchymal stem cells to restore the internal reproductive testis in male rats with azoospermia. A total of 22 rat models underwent transplantation of rat bone marrow mesenchymal stem cells into the seminiferous tubules of the testis <ref name=PMID26442294><pubmed>26442294</pubmed></ref>. Observations were made to establish differences in the structure and composition of the cells in the seminiferous tubules. Results showed that these specific stem cells are able to differentiate into germ cells and have the potential to repair seminiferous tubules that are damaged in azoospermic rats <ref name=PMID26442294><pubmed>26442294</pubmed></ref>.

====Rhesus Macaques Model====

==Glossary==

ARTs - Assisted Reproductive Technologies

Aetiological factors - causative agents

Aneuploidy - the presence of an abnormal number of chromosomes in a cell

Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production

Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonads

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism

Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome

LH - Luteinizing hormone

Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS

Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching

Quenching - the deactivation of reactive oxygen forms

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

Spermatogenesis - the production of development of new sperm

Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref>

TCM - Traditional Chinese medicine

Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref>

TMS - Total Motile Sperm

TURED - Transurethral resection of ejaculatory ducts

Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood

==References==

<references/>

2015 Group Project 4

2015-10-23T04:07:39Z

Z3463514: /* Spermatogenesis and Fertility */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref name=PMID14617369><pubmed>14617369</pubmed></ref> . Spermatozoa also consists of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes <ref name=PMID14617369><pubmed>14617369</pubmed></ref>]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa.<ref name=PMID14617369><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

===Seminiferous Tubules===

The structure of the seminiferous tubules are complex stratified epithelium which is in invested by a capsule (tunica propria) of fibroelastic tissue and flattened fibroblasts.</ref><pubmed> 26391090 </pubmed></ref>
<pubmed> 5582405</pubmed>

==Male infertility disorders==

Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may affect a different aspect of the male's sperm including sperm count, morphology and motility rates.
A fertile male is suggested to have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail.

Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly.

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref>
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|400px|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.<ref><pubmed> 26246871</pubmed></ref>]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.<ref><pubmed> 26157295</pubmed></ref>]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.<ref><pubmed>26157295</pubmed></ref>]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia <ref><pubmed>14617369</pubmed></ref>]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]

===Testicular Colour Doppler Ultrasound===
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations <ref><pubmed>24714837</pubmed></ref>]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>.

The following are a few common antioxidants that have been proven to treat oxidative stress, and hence improves male fertility.

=====1. Carotenoids=====
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>.
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments.
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>.
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below.

======Lycopenes======
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon.
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>.
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>.
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage.
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

======Astaxanthin======
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine.
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels.

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
======2. Cerium dioxide nanoparticles (CNPs)======
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>.
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>.
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

======3. Vitamin E======
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds.
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

======4. Vitamin C======
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower.
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female.
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref>
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure <ref><pubmed>18996517</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=ENrx7o_z9Ng</html5media>

IUI Treatment Procedure <ref>Indira IVF. (2014, July 27) What is IUI treatment for Pregnancy. Retrieved from https://www.youtube.com/watch?v=ENrx7o_z9Ng</ref>

====In Vitro Fertilisation (IVF)====

Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles <ref =namePMID26473112><pubmed>26473112</pubmed></ref>. Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.

Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia <ref =namePMID26473112><pubmed>26473112</pubmed></ref>.
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins.

The next step is for the oocytes and semen to undergo co-incubation <ref><pubmed>26460690</pubmed></ref>. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation.

The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues.
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. One of the most relevant clinical implications of ICSI is the ability to produce a viable embryo from an immature oocyte and a single spermatozoon injection; particularly due to the high proportion (15-20%) of oocytes retrieved when immature. <ref name=PMID26473112><pubmed>26473112</pubmed></ref>
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile <ref><pubmed>26473111</pubmed></ref>.
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes). The following shows the simplified steps of performing ICSI, and is also outlined in the video provided.
*The female is administered various hormones to stimulate ovulation to release an oocyte, then the oocyte or several oocytes are removed and stored.
*Simultaneously, the males ejaculate is also collected and only a single spermatozoa may be required for fertilisation.
*Fertilisation is acheived by the directly injecting a spermatozoon into one stored oocyte using a fine needle.
*After 2 or 3 days, if fertilisation has successfully occured, the embryo will be transferred into the female's uterus to allow for implantation, and hopefully lead to pregnancy <ref name=PMID26473112><pubmed>26473112</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media>

ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref>

===Current Research===

The research involving male infertility most recently, is surrounding more innovative techniques to identify new and different targets to treat and diagnose the condition. A study performed in September, 2015 investigated the efficacy of using sperm chromatin structure assays to determine fertility in Nigerian men <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. A total of 404 men consisting of fertile and unexplained infertile men underwent both semen analysis and sperm chromatin structure assays. Through the measurement of DNA fragmentation index, there was a more significant difference between infertile and fertile men when using sperm chromatin structure assaying <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. Therefore this new diagnostic tool may be more accurate in determining the fertility potential of males. Not only does this allow for a more predictive indicator, but it may also lead future research to use modify these technologies and perhaps find the specific molecular and cellular pathways that are affected in each individual male.

==Glossary==

ARTs - Assisted Reproductive Technologies

Aetiological factors - causative agents

Aneuploidy - the presence of an abnormal number of chromosomes in a cell

Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production

Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonads

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism

Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome

LH - Luteinizing hormone

Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS

Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching

Quenching - the deactivation of reactive oxygen forms

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

Spermatogenesis - the production of development of new sperm

Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref>

TCM - Traditional Chinese medicine

Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref>

TMS - Total Motile Sperm

TURED - Transurethral resection of ejaculatory ducts

Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood

==References==

<references/>

2015 Group Project 4

2015-10-23T02:53:54Z

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{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref><pubmed>14617369</pubmed></ref>. Spermatozoa also consists of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes <ref><pubmed>14617369</pubmed></ref>]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may affect a different aspect of the male's sperm including sperm count, morphology and motility rates.
A fertile male is suggested to have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail.

Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly.

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref>
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|400px|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.<ref><pubmed> 26246871</pubmed></ref>]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.<ref><pubmed> 26157295</pubmed></ref>]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.<ref><pubmed>26157295</pubmed></ref>]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia <ref><pubmed>14617369</pubmed></ref>]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]

===Testicular Colour Doppler Ultrasound===
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations <ref><pubmed>24714837</pubmed></ref>]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>.

The following are a few common antioxidants that have been proven to treat oxidative stress, and hence improves male fertility.

=====1. Carotenoids=====
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>.
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments.
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>.
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below.

======Lycopenes======
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon.
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>.
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>.
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage.
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

======Astaxanthin======
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine.
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels.

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
======2. Cerium dioxide nanoparticles (CNPs)======
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>.
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>.
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

======3. Vitamin E======
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds.
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

======4. Vitamin C======
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower.
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female.
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref>
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure <ref><pubmed>18996517</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=ENrx7o_z9Ng</html5media>

IUI Treatment Procedure <ref>Indira IVF. (2014, July 27) What is IUI treatment for Pregnancy. Retrieved from https://www.youtube.com/watch?v=ENrx7o_z9Ng</ref>

====In Vitro Fertilisation (IVF)====

Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles <ref =namePMID26473112><pubmed>26473112</pubmed></ref>. Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.

Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia <ref =namePMID26473112><pubmed>26473112</pubmed></ref>.
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins.

The next step is for the oocytes and semen to undergo co-incubation <ref><pubmed>26460690</pubmed></ref>. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation.

The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues.
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. One of the most relevant clinical implications of ICSI is the ability to produce a viable embryo from an immature oocyte and a single spermatozoon injection; particularly due to the high proportion (15-20%) of oocytes retrieved when immature. <ref name=PMID26473112><pubmed>26473112</pubmed></ref>
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile <ref><pubmed>26473111</pubmed></ref>.
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes). The following shows the simplified steps of performing ICSI, and is also outlined in the video provided.
*The female is administered various hormones to stimulate ovulation to release an oocyte, then the oocyte or several oocytes are removed and stored.
*Simultaneously, the males ejaculate is also collected and only a single spermatozoa may be required for fertilisation.
*Fertilisation is acheived by the directly injecting a spermatozoon into one stored oocyte using a fine needle.
*After 2 or 3 days, if fertilisation has successfully occured, the embryo will be transferred into the female's uterus to allow for implantation, and hopefully lead to pregnancy <ref name=PMID26473112><pubmed>26473112</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media>

ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref>

===Current Research===

The research involving male infertility most recently, is surrounding more innovative techniques to identify new and different targets to treat and diagnose the condition. A study performed in September, 2015 investigated the efficacy of using sperm chromatin structure assays to determine fertility in Nigerian men <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. A total of 404 men consisting of fertile and unexplained infertile men underwent both semen analysis and sperm chromatin structure assays. Through the measurement of DNA fragmentation index, there was a more significant difference between infertile and fertile men when using sperm chromatin structure assaying <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. Therefore this new diagnostic tool may be more accurate in determining the fertility potential of males. Not only does this allow for a more predictive indicator, but it may also lead future research to use modify these technologies and perhaps find the specific molecular and cellular pathways that are affected in each individual male.

==Glossary==

ARTs - Assisted Reproductive Technologies

Aetiological factors - causative agents

Aneuploidy - the presence of an abnormal number of chromosomes in a cell

Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production

Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism

Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome

LH - Luteinizing hormone

Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS

Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching

Quenching - the deactivation of reactive oxygen forms

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

Spermatogenesis - the production of development of new sperm

Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref>

TCM - Traditional Chinese medicine

Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref>

TMS - Total Motile Sperm

TURED - Transurethral resection of ejaculatory ducts

Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood

==References==

<references/>

2015 Group Project 4

2015-10-23T02:34:00Z

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{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for its transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion <ref><pubmed>14617369</pubmed></ref>. Spermatozoa also consists of a flagellum for progressive motility during its movement through the epididymal ducts and within the female reproductive organ. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes <ref><pubmed>14617369</pubmed></ref>]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may affect a different aspect of the male's sperm including sperm count, morphology and motility rates.
A fertile male is suggested to have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail.

Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly.

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref>
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.<ref><pubmed> 26246871</pubmed></ref>]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.<ref><pubmed> 26157295</pubmed></ref>]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia <ref><pubmed>14617369</pubmed></ref>]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]

===Testicular Colour Doppler Ultrasound===
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations <ref><pubmed>24714837</pubmed></ref>]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>.

The following are a few common antioxidants that have been proven to treat oxidative stress, and hence improves male fertility.

=====1. Carotenoids=====
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>.
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments.
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>.
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below.

======Lycopenes======
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon.
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>.
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>.
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage.
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

======Astaxanthin======
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine.
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels.

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
======2. Cerium dioxide nanoparticles (CNPs)======
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>.
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>.
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

======3. Vitamin E======
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds.
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

======4. Vitamin C======
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower.
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female.
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref>
The optimal conditions for an IUI include; the female being less than age 30, the male having a total motile sperm count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure <ref><pubmed>18996517</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=ENrx7o_z9Ng</html5media>

IUI Treatment Procedure <ref>Indira IVF. (2014, July 27) What is IUI treatment for Pregnancy. Retrieved from https://www.youtube.com/watch?v=ENrx7o_z9Ng</ref>

====In Vitro Fertilisation (IVF)====

Theoretically, all that is required for in vitro fertilisation is to combine the contents of a woman’s fallopian tubes and sperm, followed by re-inserting this mixture into the uterus. In practice, however, this process would be an oversimplification and not particularly successful. There are several major steps in the procedure that are necessary for pregnancy. The first step is hyperstimulation of the ovaries. The purpose of this step is to produce several oocytes to make sure there are enough suitable candidates for the procedure. This is achieved by injecting a GnRH antagonist and gonadotropins into the female. Careful monitoring of the concentrations of these hormones is essential for the safety and well-being of the patient and for the successful removal of adequate follicles <ref =namePMID26473112><pubmed>26473112</pubmed></ref>. Next, after the follicles have reached an appropriate level of development, final maturation induction is performed, typically by injection of hCG and GnRH agonist. This step is to replace the natural surge of LH that would normally mature the ovarian follicles.

Once the follicles have matured, they are retrieved from the ovaries by a process known as transvaginal oocyte retrieval <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. This involves a needle guided by ultra-sound to pierce the vaginal walls, reaching the ovaries and finally aspiration of the mature oocytes and follicular fluid. Typically, 10-30 oocytes are removed under general anaesthesia <ref =namePMID26473112><pubmed>26473112</pubmed></ref>.
The oocytes are then inspected and only those with the highest chance of successful pregnancy are chosen and the surrounding layer of cells is removed from the eggs. Semen is washed simultaneously by removing any seminal fluid and other proteins.

The next step is for the oocytes and semen to undergo co-incubation <ref><pubmed>26460690</pubmed></ref>. The sperm cells and oocytes are incubated in culture media at a ratio of 75 000:1. It is at this point that another ART may be used (ICSI) if the sperm count or motility is not optimal. Once fertilisation takes place, the egg is placed in special growth medium and left for approximately 2 days until the cell mass is around 6-8 cells.
Following this the best 2-3 embryos are selected based on a morphokinetic scoring system to increase the chances of a successful pregnancy <ref name=PMID22820320><pubmed>22820320</pubmed></ref>. Characteristics tested include the if the growth of the cells is even, the number of cells and the level of fragmentation.

The best embryos are transferred to the patient with a plastic catheter to the uterus. More than one may be transferred to increase the chances of a successful pregnancy in older women or women who have infertility issues.
In order to ensure the embryo grows normally and implants properly, the patient is given adjunctive medication. This involves injection of specific concentrations of progesterone and GnRH agonists which is performed to support the corpus luteum.

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. One of the most relevant clinical implications of ICSI is the ability to produce a viable embryo from an immature oocyte and a single spermatozoon injection; particularly due to the high proportion (15-20%) of oocytes retrieved when immature. <ref name=PMID26473112><pubmed>26473112</pubmed></ref>
ICSI is typically performed during the co-incubation stage of IVF to make sure an oocyte is properly fertilised if the sperm is immobile <ref><pubmed>26473111</pubmed></ref>.
The process involves several devices under a microscope, namely; micromanipulator, microinjectors and micropipettes). The following shows the simplified steps of performing ICSI, and is also outlined in the video provided.
*The female is administered various hormones to stimulate ovulation to release an oocyte, then the oocyte or several oocytes are removed and stored.
*Simultaneously, the males ejaculate is also collected and only a single spermatozoa may be required for fertilisation.
*Fertilisation is acheived by the directly injecting a spermatozoon into one stored oocyte using a fine needle.
*After 2 or 3 days, if fertilisation has successfully occured, the embryo will be transferred into the female's uterus to allow for implantation, and hopefully lead to pregnancy <ref name=PMID26473112><pubmed>26473112</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=h7uucZ7xpYs</html5media>

ICSI Procedure <ref>Mothercare Hosp. (2014, July 7) 3D Animation of how ICSI works. Retrieved from https://www.youtube.com/watch?v=h7uucZ7xpYs</ref>

===Current Research===

The research involving male infertility most recently, is surrounding more innovative techniques to identify new and different targets to treat and diagnose the condition. A study performed in September, 2015 investigated the efficacy of using sperm chromatin structure assays to determine fertility in Nigerian men <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. A total of 404 men consisting of fertile and unexplained infertile men underwent both semen analysis and sperm chromatin structure assays. Through the measurement of DNA fragmentation index, there was a more significant difference between infertile and fertile men when using sperm chromatin structure assaying <ref name=PMID26473109><pubmed>26473109</pubmed></ref>. Therefore this new diagnostic tool may be more accurate in determining the fertility potential of males. Not only does this allow for a more predictive indicator, but it may also lead future research to use modify these technologies and perhaps find the specific molecular and cellular pathways that are affected in each individual male.

==Glossary==

ARTs - Assisted Reproductive Technologies

Aetiological factors - causative agents

Aneuploidy - the presence of an abnormal number of chromosomes in a cell

Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production

Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism

Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome

LH - Luteinizing hormone

Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS

Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching

Quenching - the deactivation of reactive oxygen forms

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

Spermatogenesis - the production of development of new sperm

Sperm-reactive antibodies (SpAb) - antibodies present on the membrane of spermatozoa that result in adverse affects to reproduction and often infertility. <ref><pubmed>8194608</pubmed></ref>

TCM - Traditional Chinese medicine

Testicular Dysgenesis Syndrome (TDS) - a syndrome resultant of the disruption of embryonal programming and gonadal development during fetal life that is related to poor semen quality and testicular cancer, <ref><pubmed>11331648 </pubmed></ref>

TMS - Total Motile Sperm

TURED - Transurethral resection of ejaculatory ducts

Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood

==References==

<references/>

User:Z3463514

2015-10-23T01:06:31Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

Lab 10 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:03, 16 October 2015 (AEDT)

Lab 11 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:06, 23 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 7 Assessment==
 1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical. 

<pubmed>25315894</pubmed>

The pituitary gland is a major endocrine organ located at the base of the brain, it is responsible in controlling growth and development and the functioning of the other endocrine glands. The purpose of this research article was to investigate the mechanism underlying the pituitary defects. This was carried out by using different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. OTX2 is a homeo-domain transcription factor that is required for normal head development in mouse and human. Affected individuals exhibit a spectrum of features that range from developmental defects in eye or pituitary development. Mice that expresses Otx2 deficiency in early head development and pituitary oran ectoderm exhibit craniofacial defects and pituitary gland malformation at birth.

The research demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe, and extrinsic effects on anterior pituitary growth. The findings of this research suggest that mechanisms that underlie the diminished hormone secretion by the pituitary gland in patients with Otx2 mutations. The variable ocular, cranio-facial and pituitary defects that arose in Otx2 expression are consistent with the dosage sensitivity for Otx2 in early head development.

 2. Identify the embryonic layers and tissues that contribute to the developing teeth. 

Teeth development is also known as "Odontogenesis", this process commences in week 6 of embryonic development. It involves the ectoderm of the first pharyngeal arch and neural crest, ectomesenchyme.

Embryonic layers and tissues that contribute to the developing teeth:

1. Ameoblast - Epithelial cells that are derived from the oral epithelium of ectoderm and produces teeth enamel. Ameloblasts are the result from preameloblast differentiation which originate from inner enamel epithelium.

2. Odontoblasts - Mesenchymal cells which are derived from the neural crest; depending on their enamel epithelium activity they will differentiate differently. These cells produce predentin which calcifies to dentin which is found beneath the enamel in the crown region and under the cementum in within the root.

3. Periodontal ligament - It provides attachment of the teeth to the alveolar bone of the maxillae and the mandible. The periodontal ligament is composed of fibroblasts, epithelial cells, undifferentiated mesenchymal cells, bone, cementum cells and bundles of collagen fibres.

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

==Lab 9 Assessment - Permalink==

Retinal Pigment Epithelium

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2841&lon=5935&layers=B Retinal Pigment Epithelium]

Retinal pigment epithelium (RPE) cells are generated from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye. RPE are cuboidal cells with multiple villi on its apical side which are in direct contact with the outer segments of the photoreceptor cells. Its lateral sides are joined together by tight junctions, adherens and gap junctions. The basal side of the retinal pigment epithelium is in contact with the underlying basal membrane which is also known as the Bruch's membrane. The permalink shows that the sensory retina and pigmented epithelium are separated by a space called the optic ventricle. In the adult the optic ventricle will no longer be present and the 2 layers would be closely associated to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

ANAT2341 Lab 10 - Online Assessment 2015

2015-10-22T09:27:34Z

Z3463514: /* Student ROIs */

{{Header}}

==Individual Assessment==
* Place your work on this page under a sub-sub-heading of your ROI.
* Add your own sub-sub-heading '''below''' any existing student ROI.

{| class="wikitable mw-collapsible mw-collapsed"
! About this Assessment
|-
| A demonstration of this assessment will be given in the practical class. Below in the collapsible table are examples of links from a virtual slide. There is also a [[Help:Virtual Slides Permalink|permalink help page]].

{{Virtual Slide Features - Stage 22 Liver}}

Using the Human Embryo Carnegie Stage 22 [[Embryo Virtual Slides|virtual slides]] shown below:

# Using the "mobile view" Identify a sensory region of interest ('''ROI''') in one of the virtual slides below.
# View at a high magnification (detailed view) the region of interest.
# Generate a [[Help:Virtual Slides Permalink|permalink]] to the ROI.
# Paste the link on your own page and write a brief description of what the linked region is showing.
# Add a link to the embryology page and sub-heading that relates to your identified feature.
# Paste all the content (text and links) you have just generated on [[ANAT2341 Lab 10 - Online Assessment 2015|'''this page''']] under a sub-heading named after your ROI.

{|
| valign=bottom|{{SlideStage22-08}}
| valign=bottom|{{SlideStage22-08-eye}}
|-
| valign=bottom|{{SlideStage22-11}}
| valign=bottom|{{SlideStage22-15}}
|}
|}

==Student ROIs==

===This is a sub-sub-heading===

===Cochlear Duct===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-3948&lon=6149&layers=B | Cochlear Duct ]

The '''cochlear duct''' is an fluid filled cavity inside the cochlea. It located between the tympanic duct and the vestibular duct, and between the basilr membrane and reissner's memebrane. It derived from otic placode, otic vesicle, and originated from surface ectoderm.

'''embryology link''' [[Sensory - Hearing and Balance Development]] --Inner Ear

===Semicircular Canal===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-5565.50267&lon=7382.99733&layers=B | Semicircular Canal ]

The '''semicircular canals''' are part of the inner ear.They are lined with cilia and filled with endolymph which is a liquid substance. Every time the head moves, the endolymph moves the cilia and this movements of the cilia are communicated to the brain. As a result, the brain knows how to keep the body balanced, regardless of the posture.

'''embryology link''' [[Sensory - Balance Development]] -- Inner Ear

===Lens of the Eye===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2022&lon=2991&layers=B Anterior portion of the Lens of the embryonic eye]

The lens of the eye is derived from surface ectoderm. Said ectoderm forms a lens/optic placode in the head region which then invaginates to form a lens pit and then later a lens vessel. Lens fibres then develop and are surrounded by a lens capsule. The main function of the lens is to focus light onto the retina.

'''Embryology link''' [[Vision - Lens Development]] --Development Overview

===Retina of the Eye===
Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-4961.72287&lon=4821.89847&layers=B Retina of the Eye]

The retina is the light sensitive portion of the eye. It contains 10 separate layers, including the photoreceptor layer which is comprised of rods and cones. These rods and cones convert light into signals, which are then communicated to the brain via the optic nerve. Optic cup morphogenesis is responsible for the development of the vertebrate eye, and it is believed that this process significantly contributes to the development of the retina.
The image above displays a Carnegie Stage 22 retina. The nerve fibre layer is particularly prominent in this image and is the pale layer closest to the vitreous chamber. The processes of rods, cones and ganglion cells can be observed migrating towards the optic nerve.

'''Embryology Link''' [[Vision - Retina Development]]

===Retinal Pigment Epithelium===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-5391.23146&lon=3580.5&layers=B Retinal Pigment Epithelium]

The '''Retinal Pigment Epithelium (RPE)''' is a complex differentiation of the retina, is generated from the optic neuroepithelium, and is structurally made up of cuboidal cells and multiple villi on its apical side. Its lateral sides are joined together by gap junctions and adherens and the RPE's basal side is in contact with Bruch's membrane. It lies between the neuronal retina and the choroid. The section shows that in the embryo the pigmented retina is still separated by a space from the neuronal retina. This space will be decreased in the adult and closely appose the two to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

===Cornea===

Permalink: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=5&lat=-1186.66894&lon=2284.66894&layers=B Cornea]

The cornea is the front layer of the eye covering the iris, pupil and anterior chamber. The cornea is a transparent layer that accounts for 2/3 of the eyes total optic power by refracting light along with the anterior chamber and lens. The cornea in humans consist of 5 layers as shown in the permalink, the Corneal epithelium, followed by Bowman’s layer, Corneal stroma, Descemet’s membrane and corneal endothelium. The corneal stroma and endothelium are derived from cranial neural crest cells and the corneal epithelium differentiates from ectoderm interacting with the developing lens.

Embryology link: [https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Cornea_Development Vision – Cornea Development]

===Middle Ear Ossicles===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-4243.78168&lon=7877.35627&layers=B Middle Ear Ossicles]

The middle ear ossicles named the malleus, incus, and stapes, are involved in transmitting vibrations from the tympanic membrane to the oval window, and ultimately to the inner ear. The are attached to muscles, tensor tympani and stapedius, to assist in reducing sound vibration and oscillations at the oval window. Embryologically, the malleus and incus are derived from the cartilage of the 1st pharyngeal arch, and the stapes is derived from the cartilage of the 2nd pharyngeal arch. In ossicle development, the malleus and incus initially form as a single structure from Meckel's cartilage, that are later separated by joint that forms between them. This process occurs within solid mesenchyme of the pharyngeal arches, therefore the ossicles are not functioning. It is only after birth that elongation of the auditory tube occurs to form the middle ear cavity that the middle ear ossicles are situated in.

'''Embryology Link''' [[Hearing - Middle Ear Development]]

===Embryonic Tongue===
Link to permalink image: Tongue

The tongue is a muscle and is important for sensing taste. All the pharyngeal arches present in the human embryo contribute to the development of the tongue however, the tongue muscle cells are derived from somites and the muscles of mastication are derived from somitomeres. Each pharyngeal contributes a different portion where arch 1 forms the oral part of the tongue, arch 2 forms the initial transient surface, arch 3 forms the pharyngeal part of the tongue and arch 4 forms the epiglottis and adjacent regions. The superior surface of the tongue comprises of taste buds, various papillae and stratified squamous epithelium. The tongue is innervated by the hypoglossal nerve (CNXII) allowing movement.
Tongue Development

Embryonic Link: [https://embryology.med.unsw.edu.au/embryology/index.php/Tongue_Development Tongue Development]

===Retinal Pigment Epithelium (RPE)===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2841&lon=5935&layers=B Retinal Pigment Epithelium]

Retinal pigment epithelium (RPE) cells are generated from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye. RPE are cuboidal cells with multiple villi on its apical side which are in direct contact with the outer segments of the photoreceptor cells. Its lateral sides are joined together by tight junctions, adherens and gap junctions. The basal side of the retinal pigment epithelium is in contact with the underlying basal membrane which is also known as the Bruch's membrane. The permalink shows that the sensory retina and pigmented epithelium are separated by a space called the optic ventricle. In the adult the optic ventricle will no longer be present and the 2 layers would be closely associated to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

{{ANAT2341Lab10}}

{{2015ANAT2341}}

ANAT2341 Lab 10 - Online Assessment 2015

2015-10-22T09:26:55Z

Z3463514: /* Student ROIs */

{{Header}}

==Individual Assessment==
* Place your work on this page under a sub-sub-heading of your ROI.
* Add your own sub-sub-heading '''below''' any existing student ROI.

{| class="wikitable mw-collapsible mw-collapsed"
! About this Assessment
|-
| A demonstration of this assessment will be given in the practical class. Below in the collapsible table are examples of links from a virtual slide. There is also a [[Help:Virtual Slides Permalink|permalink help page]].

{{Virtual Slide Features - Stage 22 Liver}}

Using the Human Embryo Carnegie Stage 22 [[Embryo Virtual Slides|virtual slides]] shown below:

# Using the "mobile view" Identify a sensory region of interest ('''ROI''') in one of the virtual slides below.
# View at a high magnification (detailed view) the region of interest.
# Generate a [[Help:Virtual Slides Permalink|permalink]] to the ROI.
# Paste the link on your own page and write a brief description of what the linked region is showing.
# Add a link to the embryology page and sub-heading that relates to your identified feature.
# Paste all the content (text and links) you have just generated on [[ANAT2341 Lab 10 - Online Assessment 2015|'''this page''']] under a sub-heading named after your ROI.

{|
| valign=bottom|{{SlideStage22-08}}
| valign=bottom|{{SlideStage22-08-eye}}
|-
| valign=bottom|{{SlideStage22-11}}
| valign=bottom|{{SlideStage22-15}}
|}
|}

==Student ROIs==

===This is a sub-sub-heading===

===Cochlear Duct===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-3948&lon=6149&layers=B | Cochlear Duct ]

The '''cochlear duct''' is an fluid filled cavity inside the cochlea. It located between the tympanic duct and the vestibular duct, and between the basilr membrane and reissner's memebrane. It derived from otic placode, otic vesicle, and originated from surface ectoderm.

'''embryology link''' [[Sensory - Hearing and Balance Development]] --Inner Ear

===Semicircular Canal===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-5565.50267&lon=7382.99733&layers=B | Semicircular Canal ]

The '''semicircular canals''' are part of the inner ear.They are lined with cilia and filled with endolymph which is a liquid substance. Every time the head moves, the endolymph moves the cilia and this movements of the cilia are communicated to the brain. As a result, the brain knows how to keep the body balanced, regardless of the posture.

'''embryology link''' [[Sensory - Balance Development]] -- Inner Ear

===Lens of the Eye===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2022&lon=2991&layers=B Anterior portion of the Lens of the embryonic eye]

The lens of the eye is derived from surface ectoderm. Said ectoderm forms a lens/optic placode in the head region which then invaginates to form a lens pit and then later a lens vessel. Lens fibres then develop and are surrounded by a lens capsule. The main function of the lens is to focus light onto the retina.

'''Embryology link''' [[Vision - Lens Development]] --Development Overview

===Retina of the Eye===
Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-4961.72287&lon=4821.89847&layers=B Retina of the Eye]

The retina is the light sensitive portion of the eye. It contains 10 separate layers, including the photoreceptor layer which is comprised of rods and cones. These rods and cones convert light into signals, which are then communicated to the brain via the optic nerve. Optic cup morphogenesis is responsible for the development of the vertebrate eye, and it is believed that this process significantly contributes to the development of the retina.
The image above displays a Carnegie Stage 22 retina. The nerve fibre layer is particularly prominent in this image and is the pale layer closest to the vitreous chamber. The processes of rods, cones and ganglion cells can be observed migrating towards the optic nerve.

'''Embryology Link''' [[Vision - Retina Development]]

===Retinal Pigment Epithelium===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-5391.23146&lon=3580.5&layers=B Retinal Pigment Epithelium]

The '''Retinal Pigment Epithelium (RPE)''' is a complex differentiation of the retina, is generated from the optic neuroepithelium, and is structurally made up of cuboidal cells and multiple villi on its apical side. Its lateral sides are joined together by gap junctions and adherens and the RPE's basal side is in contact with Bruch's membrane. It lies between the neuronal retina and the choroid. The section shows that in the embryo the pigmented retina is still separated by a space from the neuronal retina. This space will be decreased in the adult and closely appose the two to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

===Cornea===

Permalink: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=5&lat=-1186.66894&lon=2284.66894&layers=B Cornea]

The cornea is the front layer of the eye covering the iris, pupil and anterior chamber. The cornea is a transparent layer that accounts for 2/3 of the eyes total optic power by refracting light along with the anterior chamber and lens. The cornea in humans consist of 5 layers as shown in the permalink, the Corneal epithelium, followed by Bowman’s layer, Corneal stroma, Descemet’s membrane and corneal endothelium. The corneal stroma and endothelium are derived from cranial neural crest cells and the corneal epithelium differentiates from ectoderm interacting with the developing lens.

Embryology link: [https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Cornea_Development Vision – Cornea Development]

===Middle Ear Ossicles===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-4243.78168&lon=7877.35627&layers=B Middle Ear Ossicles]

The middle ear ossicles named the malleus, incus, and stapes, are involved in transmitting vibrations from the tympanic membrane to the oval window, and ultimately to the inner ear. The are attached to muscles, tensor tympani and stapedius, to assist in reducing sound vibration and oscillations at the oval window. Embryologically, the malleus and incus are derived from the cartilage of the 1st pharyngeal arch, and the stapes is derived from the cartilage of the 2nd pharyngeal arch. In ossicle development, the malleus and incus initially form as a single structure from Meckel's cartilage, that are later separated by joint that forms between them. This process occurs within solid mesenchyme of the pharyngeal arches, therefore the ossicles are not functioning. It is only after birth that elongation of the auditory tube occurs to form the middle ear cavity that the middle ear ossicles are situated in.

'''Embryology Link''' [[Hearing - Middle Ear Development]]

===Embryonic Tongue===
Link to permalink image: Tongue

The tongue is a muscle and is important for sensing taste. All the pharyngeal arches present in the human embryo contribute to the development of the tongue however, the tongue muscle cells are derived from somites and the muscles of mastication are derived from somitomeres. Each pharyngeal contributes a different portion where arch 1 forms the oral part of the tongue, arch 2 forms the initial transient surface, arch 3 forms the pharyngeal part of the tongue and arch 4 forms the epiglottis and adjacent regions. The superior surface of the tongue comprises of taste buds, various papillae and stratified squamous epithelium. The tongue is innervated by the hypoglossal nerve (CNXII) allowing movement.
Tongue Development

Embryonic Link: [https://embryology.med.unsw.edu.au/embryology/index.php/Tongue_Development Tongue Development]
 
===Retinal Pigment Epithelium (RPE)===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2841&lon=5935&layers=B Retinal Pigment Epithelium]

Retinal pigment epithelium (RPE) cells are generated from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye. RPE are cuboidal cells with multiple villi on its apical side which are in direct contact with the outer segments of the photoreceptor cells. Its lateral sides are joined together by tight junctions, adherens and gap junctions. The basal side of the retinal pigment epithelium is in contact with the underlying basal membrane which is also known as the Bruch's membrane. The permalink shows that the sensory retina and pigmented epithelium are separated by a space called the optic ventricle. In the adult the optic ventricle will no longer be present and the 2 layers would be closely associated to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

{{ANAT2341Lab10}}

{{2015ANAT2341}}

ANAT2341 Lab 10 - Online Assessment 2015

2015-10-22T09:26:32Z

Z3463514: /* Student ROIs */

{{Header}}

==Individual Assessment==
* Place your work on this page under a sub-sub-heading of your ROI.
* Add your own sub-sub-heading '''below''' any existing student ROI.

{| class="wikitable mw-collapsible mw-collapsed"
! About this Assessment
|-
| A demonstration of this assessment will be given in the practical class. Below in the collapsible table are examples of links from a virtual slide. There is also a [[Help:Virtual Slides Permalink|permalink help page]].

{{Virtual Slide Features - Stage 22 Liver}}

Using the Human Embryo Carnegie Stage 22 [[Embryo Virtual Slides|virtual slides]] shown below:

# Using the "mobile view" Identify a sensory region of interest ('''ROI''') in one of the virtual slides below.
# View at a high magnification (detailed view) the region of interest.
# Generate a [[Help:Virtual Slides Permalink|permalink]] to the ROI.
# Paste the link on your own page and write a brief description of what the linked region is showing.
# Add a link to the embryology page and sub-heading that relates to your identified feature.
# Paste all the content (text and links) you have just generated on [[ANAT2341 Lab 10 - Online Assessment 2015|'''this page''']] under a sub-heading named after your ROI.

{|
| valign=bottom|{{SlideStage22-08}}
| valign=bottom|{{SlideStage22-08-eye}}
|-
| valign=bottom|{{SlideStage22-11}}
| valign=bottom|{{SlideStage22-15}}
|}
|}

==Student ROIs==

===This is a sub-sub-heading===

===Cochlear Duct===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-3948&lon=6149&layers=B | Cochlear Duct ]

The '''cochlear duct''' is an fluid filled cavity inside the cochlea. It located between the tympanic duct and the vestibular duct, and between the basilr membrane and reissner's memebrane. It derived from otic placode, otic vesicle, and originated from surface ectoderm.

'''embryology link''' [[Sensory - Hearing and Balance Development]] --Inner Ear

===Semicircular Canal===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-5565.50267&lon=7382.99733&layers=B | Semicircular Canal ]

The '''semicircular canals''' are part of the inner ear.They are lined with cilia and filled with endolymph which is a liquid substance. Every time the head moves, the endolymph moves the cilia and this movements of the cilia are communicated to the brain. As a result, the brain knows how to keep the body balanced, regardless of the posture.

'''embryology link''' [[Sensory - Balance Development]] -- Inner Ear

===Lens of the Eye===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2022&lon=2991&layers=B Anterior portion of the Lens of the embryonic eye]

The lens of the eye is derived from surface ectoderm. Said ectoderm forms a lens/optic placode in the head region which then invaginates to form a lens pit and then later a lens vessel. Lens fibres then develop and are surrounded by a lens capsule. The main function of the lens is to focus light onto the retina.

'''Embryology link''' [[Vision - Lens Development]] --Development Overview

===Retina of the Eye===
Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-4961.72287&lon=4821.89847&layers=B Retina of the Eye]

The retina is the light sensitive portion of the eye. It contains 10 separate layers, including the photoreceptor layer which is comprised of rods and cones. These rods and cones convert light into signals, which are then communicated to the brain via the optic nerve. Optic cup morphogenesis is responsible for the development of the vertebrate eye, and it is believed that this process significantly contributes to the development of the retina.
The image above displays a Carnegie Stage 22 retina. The nerve fibre layer is particularly prominent in this image and is the pale layer closest to the vitreous chamber. The processes of rods, cones and ganglion cells can be observed migrating towards the optic nerve.

'''Embryology Link''' [[Vision - Retina Development]]

===Retinal Pigment Epithelium===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-5391.23146&lon=3580.5&layers=B Retinal Pigment Epithelium]

The '''Retinal Pigment Epithelium (RPE)''' is a complex differentiation of the retina, is generated from the optic neuroepithelium, and is structurally made up of cuboidal cells and multiple villi on its apical side. Its lateral sides are joined together by gap junctions and adherens and the RPE's basal side is in contact with Bruch's membrane. It lies between the neuronal retina and the choroid. The section shows that in the embryo the pigmented retina is still separated by a space from the neuronal retina. This space will be decreased in the adult and closely appose the two to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

===Cornea===

Permalink: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=5&lat=-1186.66894&lon=2284.66894&layers=B Cornea]

The cornea is the front layer of the eye covering the iris, pupil and anterior chamber. The cornea is a transparent layer that accounts for 2/3 of the eyes total optic power by refracting light along with the anterior chamber and lens. The cornea in humans consist of 5 layers as shown in the permalink, the Corneal epithelium, followed by Bowman’s layer, Corneal stroma, Descemet’s membrane and corneal endothelium. The corneal stroma and endothelium are derived from cranial neural crest cells and the corneal epithelium differentiates from ectoderm interacting with the developing lens.

Embryology link: [https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Cornea_Development Vision – Cornea Development]

===Middle Ear Ossicles===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-4243.78168&lon=7877.35627&layers=B Middle Ear Ossicles]

The middle ear ossicles named the malleus, incus, and stapes, are involved in transmitting vibrations from the tympanic membrane to the oval window, and ultimately to the inner ear. The are attached to muscles, tensor tympani and stapedius, to assist in reducing sound vibration and oscillations at the oval window. Embryologically, the malleus and incus are derived from the cartilage of the 1st pharyngeal arch, and the stapes is derived from the cartilage of the 2nd pharyngeal arch. In ossicle development, the malleus and incus initially form as a single structure from Meckel's cartilage, that are later separated by joint that forms between them. This process occurs within solid mesenchyme of the pharyngeal arches, therefore the ossicles are not functioning. It is only after birth that elongation of the auditory tube occurs to form the middle ear cavity that the middle ear ossicles are situated in.

'''Embryology Link''' [[Hearing - Middle Ear Development]]

===Embryonic Tongue===
Link to permalink image: Tongue

The tongue is a muscle and is important for sensing taste. All the pharyngeal arches present in the human embryo contribute to the development of the tongue however, the tongue muscle cells are derived from somites and the muscles of mastication are derived from somitomeres. Each pharyngeal contributes a different portion where arch 1 forms the oral part of the tongue, arch 2 forms the initial transient surface, arch 3 forms the pharyngeal part of the tongue and arch 4 forms the epiglottis and adjacent regions. The superior surface of the tongue comprises of taste buds, various papillae and stratified squamous epithelium. The tongue is innervated by the hypoglossal nerve (CNXII) allowing movement.
Tongue Development

Embryonic Link: [https://embryology.med.unsw.edu.au/embryology/index.php/Tongue_Development Tongue Development]
 

===Retinal Pigment Epithelium (RPE)===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2841&lon=5935&layers=B Retinal Pigment Epithelium]

Retinal pigment epithelium (RPE) cells are generated from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye. RPE are cuboidal cells with multiple villi on its apical side which are in direct contact with the outer segments of the photoreceptor cells. Its lateral sides are joined together by tight junctions, adherens and gap junctions. The basal side of the retinal pigment epithelium is in contact with the underlying basal membrane which is also known as the Bruch's membrane. The permalink shows that the sensory retina and pigmented epithelium are separated by a space called the optic ventricle. In the adult the optic ventricle will no longer be present and the 2 layers would be closely associated to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

{{ANAT2341Lab10}}

{{2015ANAT2341}}

ANAT2341 Lab 10 - Online Assessment 2015

2015-10-22T09:25:50Z

Z3463514: /* Student ROIs */

{{Header}}

==Individual Assessment==
* Place your work on this page under a sub-sub-heading of your ROI.
* Add your own sub-sub-heading '''below''' any existing student ROI.

{| class="wikitable mw-collapsible mw-collapsed"
! About this Assessment
|-
| A demonstration of this assessment will be given in the practical class. Below in the collapsible table are examples of links from a virtual slide. There is also a [[Help:Virtual Slides Permalink|permalink help page]].

{{Virtual Slide Features - Stage 22 Liver}}

Using the Human Embryo Carnegie Stage 22 [[Embryo Virtual Slides|virtual slides]] shown below:

# Using the "mobile view" Identify a sensory region of interest ('''ROI''') in one of the virtual slides below.
# View at a high magnification (detailed view) the region of interest.
# Generate a [[Help:Virtual Slides Permalink|permalink]] to the ROI.
# Paste the link on your own page and write a brief description of what the linked region is showing.
# Add a link to the embryology page and sub-heading that relates to your identified feature.
# Paste all the content (text and links) you have just generated on [[ANAT2341 Lab 10 - Online Assessment 2015|'''this page''']] under a sub-heading named after your ROI.

{|
| valign=bottom|{{SlideStage22-08}}
| valign=bottom|{{SlideStage22-08-eye}}
|-
| valign=bottom|{{SlideStage22-11}}
| valign=bottom|{{SlideStage22-15}}
|}
|}

==Student ROIs==

===This is a sub-sub-heading===

===Cochlear Duct===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-3948&lon=6149&layers=B | Cochlear Duct ]

The '''cochlear duct''' is an fluid filled cavity inside the cochlea. It located between the tympanic duct and the vestibular duct, and between the basilr membrane and reissner's memebrane. It derived from otic placode, otic vesicle, and originated from surface ectoderm.

'''embryology link''' [[Sensory - Hearing and Balance Development]] --Inner Ear

===Semicircular Canal===

link to permalink image:[https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-5565.50267&lon=7382.99733&layers=B | Semicircular Canal ]

The '''semicircular canals''' are part of the inner ear.They are lined with cilia and filled with endolymph which is a liquid substance. Every time the head moves, the endolymph moves the cilia and this movements of the cilia are communicated to the brain. As a result, the brain knows how to keep the body balanced, regardless of the posture.

'''embryology link''' [[Sensory - Balance Development]] -- Inner Ear

===Lens of the Eye===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2022&lon=2991&layers=B Anterior portion of the Lens of the embryonic eye]

The lens of the eye is derived from surface ectoderm. Said ectoderm forms a lens/optic placode in the head region which then invaginates to form a lens pit and then later a lens vessel. Lens fibres then develop and are surrounded by a lens capsule. The main function of the lens is to focus light onto the retina.

'''Embryology link''' [[Vision - Lens Development]] --Development Overview

===Retina of the Eye===
Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-4961.72287&lon=4821.89847&layers=B Retina of the Eye]

The retina is the light sensitive portion of the eye. It contains 10 separate layers, including the photoreceptor layer which is comprised of rods and cones. These rods and cones convert light into signals, which are then communicated to the brain via the optic nerve. Optic cup morphogenesis is responsible for the development of the vertebrate eye, and it is believed that this process significantly contributes to the development of the retina.
The image above displays a Carnegie Stage 22 retina. The nerve fibre layer is particularly prominent in this image and is the pale layer closest to the vitreous chamber. The processes of rods, cones and ganglion cells can be observed migrating towards the optic nerve.

'''Embryology Link''' [[Vision - Retina Development]]

===Retinal Pigment Epithelium===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-5391.23146&lon=3580.5&layers=B Retinal Pigment Epithelium]

The '''Retinal Pigment Epithelium (RPE)''' is a complex differentiation of the retina, is generated from the optic neuroepithelium, and is structurally made up of cuboidal cells and multiple villi on its apical side. Its lateral sides are joined together by gap junctions and adherens and the RPE's basal side is in contact with Bruch's membrane. It lies between the neuronal retina and the choroid. The section shows that in the embryo the pigmented retina is still separated by a space from the neuronal retina. This space will be decreased in the adult and closely appose the two to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

===Cornea===

Permalink: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=5&lat=-1186.66894&lon=2284.66894&layers=B Cornea]

The cornea is the front layer of the eye covering the iris, pupil and anterior chamber. The cornea is a transparent layer that accounts for 2/3 of the eyes total optic power by refracting light along with the anterior chamber and lens. The cornea in humans consist of 5 layers as shown in the permalink, the Corneal epithelium, followed by Bowman’s layer, Corneal stroma, Descemet’s membrane and corneal endothelium. The corneal stroma and endothelium are derived from cranial neural crest cells and the corneal epithelium differentiates from ectoderm interacting with the developing lens.

Embryology link: [https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Cornea_Development Vision – Cornea Development]

===Middle Ear Ossicles===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/11/Stage22-11.html?zoom=6&lat=-4243.78168&lon=7877.35627&layers=B Middle Ear Ossicles]

The middle ear ossicles named the malleus, incus, and stapes, are involved in transmitting vibrations from the tympanic membrane to the oval window, and ultimately to the inner ear. The are attached to muscles, tensor tympani and stapedius, to assist in reducing sound vibration and oscillations at the oval window. Embryologically, the malleus and incus are derived from the cartilage of the 1st pharyngeal arch, and the stapes is derived from the cartilage of the 2nd pharyngeal arch. In ossicle development, the malleus and incus initially form as a single structure from Meckel's cartilage, that are later separated by joint that forms between them. This process occurs within solid mesenchyme of the pharyngeal arches, therefore the ossicles are not functioning. It is only after birth that elongation of the auditory tube occurs to form the middle ear cavity that the middle ear ossicles are situated in.

'''Embryology Link''' [[Hearing - Middle Ear Development]]

===Embryonic Tongue===
Link to permalink image: Tongue

The tongue is a muscle and is important for sensing taste. All the pharyngeal arches present in the human embryo contribute to the development of the tongue however, the tongue muscle cells are derived from somites and the muscles of mastication are derived from somitomeres. Each pharyngeal contributes a different portion where arch 1 forms the oral part of the tongue, arch 2 forms the initial transient surface, arch 3 forms the pharyngeal part of the tongue and arch 4 forms the epiglottis and adjacent regions. The superior surface of the tongue comprises of taste buds, various papillae and stratified squamous epithelium. The tongue is innervated by the hypoglossal nerve (CNXII) allowing movement.
Tongue Development

Embryonic Link: [https://embryology.med.unsw.edu.au/embryology/index.php/Tongue_Development Tongue Development]
 
{{ANAT2341Lab10}}

===Retinal Pigment Epithelium (RPE)===

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2841&lon=5935&layers=B Retinal Pigment Epithelium]

Retinal pigment epithelium (RPE) cells are generated from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye. RPE are cuboidal cells with multiple villi on its apical side which are in direct contact with the outer segments of the photoreceptor cells. Its lateral sides are joined together by tight junctions, adherens and gap junctions. The basal side of the retinal pigment epithelium is in contact with the underlying basal membrane which is also known as the Bruch's membrane. The permalink shows that the sensory retina and pigmented epithelium are separated by a space called the optic ventricle. In the adult the optic ventricle will no longer be present and the 2 layers would be closely associated to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

{{2015ANAT2341}}

User:Z3463514

2015-10-22T09:25:22Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

Lab 10 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:03, 16 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 7 Assessment==
 1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical. 

<pubmed>25315894</pubmed>

The pituitary gland is a major endocrine organ located at the base of the brain, it is responsible in controlling growth and development and the functioning of the other endocrine glands. The purpose of this research article was to investigate the mechanism underlying the pituitary defects. This was carried out by using different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. OTX2 is a homeo-domain transcription factor that is required for normal head development in mouse and human. Affected individuals exhibit a spectrum of features that range from developmental defects in eye or pituitary development. Mice that expresses Otx2 deficiency in early head development and pituitary oran ectoderm exhibit craniofacial defects and pituitary gland malformation at birth.

The research demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe, and extrinsic effects on anterior pituitary growth. The findings of this research suggest that mechanisms that underlie the diminished hormone secretion by the pituitary gland in patients with Otx2 mutations. The variable ocular, cranio-facial and pituitary defects that arose in Otx2 expression are consistent with the dosage sensitivity for Otx2 in early head development.

 2. Identify the embryonic layers and tissues that contribute to the developing teeth. 

Teeth development is also known as "Odontogenesis", this process commences in week 6 of embryonic development. It involves the ectoderm of the first pharyngeal arch and neural crest, ectomesenchyme.

Embryonic layers and tissues that contribute to the developing teeth:

1. Ameoblast - Epithelial cells that are derived from the oral epithelium of ectoderm and produces teeth enamel. Ameloblasts are the result from preameloblast differentiation which originate from inner enamel epithelium.

2. Odontoblasts - Mesenchymal cells which are derived from the neural crest; depending on their enamel epithelium activity they will differentiate differently. These cells produce predentin which calcifies to dentin which is found beneath the enamel in the crown region and under the cementum in within the root.

3. Periodontal ligament - It provides attachment of the teeth to the alveolar bone of the maxillae and the mandible. The periodontal ligament is composed of fibroblasts, epithelial cells, undifferentiated mesenchymal cells, bone, cementum cells and bundles of collagen fibres.

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

==Lab 9 Assessment - Permalink==

Retinal Pigment Epithelium

Link to permalink image: [https://embryology.med.unsw.edu.au/embryology/Slides/Embryo_Stages/Stage22/08-eye/Stage22-08-eye.html?zoom=6&lat=-2841&lon=5935&layers=B Retinal Pigment Epithelium]

Retinal pigment epithelium (RPE) cells are generated from the optic neuroepithelium. The choroidal melanocytes, the other pigmented cells, are derived from neural crest cells that have migrated towards the eye. RPE are cuboidal cells with multiple villi on its apical side which are in direct contact with the outer segments of the photoreceptor cells. Its lateral sides are joined together by tight junctions, adherens and gap junctions. The basal side of the retinal pigment epithelium is in contact with the underlying basal membrane which is also known as the Bruch's membrane. The permalink shows that the sensory retina and pigmented epithelium are separated by a space called the optic ventricle. In the adult the optic ventricle will no longer be present and the 2 layers would be closely associated to each other.

'''Embryology Link''' [[Vision - Retina Development#Retinal Pigment Epithelium]]

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

2015 Group Project 4

2015-10-22T06:35:23Z

Z3463514: /* Intrauterine Insemination (IUI) */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

Although infertility refers to the inability to conceive, there are numerous disorders that address particular reasons as to why this is the case. For males, the causes of infertility are endless and the most common factors have been discussed previously. Due to the range of aetiological factors, each one may effect a different aspect of the male's sperm including sperm count, morphology and motility rates.
A fertile male is suggested have normospermia <ref><pubmed>PMC4156950</pubmed></ref> , in which the male's ejaculate contains normal sperm quality and quantity which are (based on the World Health Organisation (WHO)):
*Ejaculate volume of approximately 1.5 to 5 mL <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Count of approximately 15 million to over 200 million spermatozoa per mL of ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Progressive motility of 32% or more spermatozoa <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>.
*Normal morphology present in 4% of the ejaculate <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>, in which normal form refers to the spermatozoa containing the 3 fundamental parts; a head, midpiece and tail.

Based on WHO's normal semen analysis, the specific types of male infertility disorders have been categorised accordingly.

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count of less than 15 million sperm/mL of ejaculate <ref><pubmed>23757979</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen with a progressive motility of less than 20% <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| More than 95% of spermatozoa in the ejaculate has abnormal morphology <ref name=Escobar>Escobar, J. (2013). New Semen Analysis Parameters - WHO - World Health Organization. Fertility Center in Irving and Arlington. Retrieved 20 October 2015, from http://ivfmd.net/new-world-health-semen-analysis-parameters/</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia) (referring to the statistics mentioned for each condition)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa, despite normal spermatogenesis within the semen due to a blockage in the genital tract, obstructing the pathway for sperm to enter the penis from the testes <ref><pubmed>PMC3583161</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to the abnormal process or failure of spermatogenesis occurring, whereby sperm producing cells being damaged or destroyed <ref><pubmed>PMC3583162</pubmed></ref>
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]

===Testicular Colour Doppler Ultrasound===
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. The associated image demonstrates the development and availability of gonadotropins for commercial use.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>.

The following are a few antioxidants that have been proven to treat oxidative stress, and hence improves male fertility.

=====1. Carotenoids=====
*Naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>.
*Subtypes are divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>
*Main source of carotenoids in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments.
*Have been suggested as daily supplements for the human body, and act as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>.
*Their antioxidant activity of is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

Two common carotenoids that have been strongly advised as treatments for male infertility include lycopenes and Astaxanthin, described below.

======Lycopenes======
*Type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon.
*Possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>.
*Have a role in neutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>.
*Inhibit lipid peroxidation allowing for spermatozoal membranes to be retained and protected from further damage.
*Suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

======Astaxanthin======
*Keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. it has been
*Suggested as an effective treatment and supplement for male factor infertility due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine.
*An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for increased motility concentration, improved sperm morphology and motility, and a decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels.

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
=====2. Cerium dioxide nanoparticles (CNPs)=====
*Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility.
*They are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>.
*CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>.
*A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

=====3. Vitamin E=====
*A fat – soluble antioxidant that exists in 8 chemical forms of different biological activity.
*The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>, found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*The recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>.
*Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds.
*From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

=====4. Vitamin C=====
*A water-soluble antioxidant that neutralizes free radicals and also prevents ROS synthesis<ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*The human body does not produce or store vitamin C, so daily intakes of vitamin C – containing foods are required to maintain its levels internally.The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>.
*Foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower.
*A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

Intrauterine insemination (IUI) is a simple procedure performed by a medical practitioner where washed sperm is injected directly into the uterus with a catheter. This allows the sperm to get as close to the egg as possible, increasing the chances of reaching it. This method is known as in vivo fertilisation as it is performed within the body of the female.
It has been shown that if the woman rests for up to 15 minutes after insemination the chance of pregnancy is greater than if they are mobilised immediately after the procedure.<ref><pubmed>19875843</pubmed></ref>
The optimal conditions for an IUI include; the female being less than age 30, the male having a TMS count of more than 5 million per mL. A likely pregnancy will result from a cycle that produces two eggs of 16 mm or more and an oestrogen concentration of 500 pg/mL at the time of the procedure.<ref><pubmed>18996517</pubmed></ref>

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==Glossary==

ARTs - Assisted Reproductive Technologies

Aetiological factors - causative agents

Cadmium - a soft, insoluble transition metal that is a byproduct of zinc production

Clomiphene citrate - a non-steroidal medication that induces infertility by increasing the release of GnRH, LH and FSH required for spermatogenesis

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

Gametogenesis - a biological process resulting in the formation of mature haploid male (spermatogenesis) and female (oogenesis) germ cells

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

Hypogonadatropic hypogonadism - a condition characterised by a decrease in functional activity of the gonadH

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

Kiss1 - KiSS-1 Metastasis-Suppressor; a gene that codes for Kisspeptin, a G protein coupled receptor associated with hypogonadotropic hypogonadism

Klinefelter syndrome - genetic disorder whereby a male has an extra X chromosome

LH - Luteinizing hormone

Lipid peroxidation - the oxidation of lipids causing its degradation, usually caused by ROS

Progressive motility - the swimming of sperm from one place to another rather than in circles or twitching

Quenching - the deactivation of reactive oxygen forms

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

SpAb - Sperm-reactive antibodies

TCM - Traditional Chinese medicine

TDS - Testicular Dysgenesis Syndrome

TMS - Total Motile Sperm

TURED - Transurethral resection of ejaculatory ducts

Varicocele - Abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood

==References==

<references/>

==External Resources==

2015 Group Project 4

2015-10-19T22:16:14Z

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{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. It is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

Due to the growing issue, this page will discuss the most common causes, diagnostic tools, and treatments of male infertility, and ultimately provide a scope of the topic to allow for further research to improve our current understanding of what infertility entails.

==Spermatogenesis and Fertility==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|left|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=QdIl1TjUvIQ</html5media>

Male Infertility <ref>Healthguru. (2008, January 4) Male Infertility (Getting Pregnant #3). Retrieved from https://www.youtube.com/watch?v=QdIl1TjUvIQ </ref>

===Major Causes of Male Infertility===
[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|left| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

====Varicocele====
Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|left|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]

===Testicular Colour Doppler Ultrasound===
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

If sufferers addressed the above risk factors, this would allow for safe and effective prevention of male infertility as a whole, or prevent the condition from getting worse.

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|left|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocelectomy====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

<html5media height="300" width="400">https://www.youtube.com/watch?v=3crlbOiCO48</html5media>

Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals <ref>Manipal Hospitals. (2015, May 19) Varicocelectomy | Testicular Diseases | Male Infertility | Urinary Problems | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=3crlbOiCO48 </ref>

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval. The following video demonstrates some common techniques that have been used to successfully retrieve sperm.

<html5media height="300" width="400">https://www.youtube.com/watch?v=c_nK2ZS_Mr0</html5media>

Sperm Retrieval Procedures <ref>Manipal Hospitals. (2015, May 19) Sperm Retrieval IVF | Male Infertility | Infertility Treatment | Manipal Hospitals. Retrieved from https://www.youtube.com/watch?v=c_nK2ZS_Mr0 </ref>

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==Glossary==

ARTs - Assisted Reproductive Technologies

CNPs - Cerium dioxide nanoparticles

FSH - Follicle stimulating hormone

GnRH - Gonadotropin releasing hormone

hCG - Human chorionic gonadotropin

hMG - Human menopausal gonadotropin

ICSI - Intracytoplasmic Sperm Injection

IUI - Intrauterine Insemination

IVF - In Vitro Fertilisation

LH - Luteinizing hormone

RDA - Recommended dietary allowance

ROS - Reactive oxygen species

SpAb - Sperm-reactive antibodies

TCM - Traditional Chinese medicine

TDS - Testicular Dysgenesis Syndrome

TURED - Transurethral resection of ejaculatory ducts

==References==

<references/>

==External Resources==

2015 Group Project 4

2015-10-19T13:22:33Z

Z3463514: /* Background Information */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

==Background Information==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|Spermatozoon which is made up of two main regions, the head and the tail. ]]
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|right|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=joTrmeDf1dY</html5media>

Infertility: Causes Behind Infertility <ref>St Pete Urology. (2011, September 14) Infertility: Causes Behind Infertility. Retrieved from https://www.youtube.com/watch?v=joTrmeDf1dY </ref>

===Major Causes of Male Infertility===

====Varicocele====

[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|right| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|right|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|right|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocele Surgery====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval.

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==References==

<references/>

==External Resources==

2015 Group Project 4

2015-10-19T13:21:29Z

Z3463514: /* Background Information */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

==Background Information==
[[File:Structure of mouse spermatozoa.jpeg|600px|thumb|right|Spermatozoon which is made up of two main regions, the head and the tail. ]]
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|right|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=joTrmeDf1dY</html5media>

Infertility: Causes Behind Infertility <ref>St Pete Urology. (2011, September 14) Infertility: Causes Behind Infertility. Retrieved from https://www.youtube.com/watch?v=joTrmeDf1dY </ref>

===Major Causes of Male Infertility===

====Varicocele====

[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|right| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|right|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|right|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocele Surgery====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval.

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==References==

<references/>

==External Resources==

2015 Group Project 4

2015-10-19T13:19:56Z

Z3463514: /* Background Information */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

==Background Information==
[[File:Structure of mouse spermatozoa.jpeg|300px|thumb|right|Spermatozoon which is made up of two main regions, the head and the tail. The anterior portion of the head is covered by the acrosomal cap, containing active enzymes to degrade the zone pellucida of the oocyte; and the head is joined to the tail by the connecting piece. The tail is divided into three regions: the mid piece (mitochondrial sheath); principal piece; and the end-piece]]
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|right|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=joTrmeDf1dY</html5media>

Infertility: Causes Behind Infertility <ref>St Pete Urology. (2011, September 14) Infertility: Causes Behind Infertility. Retrieved from https://www.youtube.com/watch?v=joTrmeDf1dY </ref>

===Major Causes of Male Infertility===

====Varicocele====

[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|right| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|right|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|right|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocele Surgery====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval.

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==References==

<references/>

==External Resources==

File:Structure of mouse spermatozoa.jpeg

2015-10-19T13:16:33Z

Z3463514: "Structure of a mouse spermatozoa" A labelled image of the the spermatozoon which is made up of two main regions, the head and the tail. The anterior portion of the head is covered by the acrosomal cap, containing active enzymes to degrade the zone pel...

"Structure of a mouse spermatozoa" A labelled image of the the spermatozoon which is made up of two main regions, the head and the tail. The anterior portion of the head is covered by the acrosomal cap, containing active enzymes to degrade the zone pellucida of the oocyte; and the head is joined to the tail by the connecting piece. The tail is divided into three regions: the mid piece (mitochondrial sheath); principal piece; and the end-piece.. Drawn by student z3463514.

===Reference===
Mark Hill - Lecture 2 "Fertilisation"

<pubmed>19758979</pubmed>

"Beginning six months after publication, I z3463514 grant the public the non-exclusive right to copy, distribute, or display the Work under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ and http://creativecommons.org/licenses/by-nc-sa/3.0/legalcode."

Image_(3).jpg

{{Template:Student Image}}

User:Z3463514

2015-10-19T06:46:53Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

Lab 10 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:03, 16 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 7 Assessment==
 1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical. 

<pubmed>25315894</pubmed>

The pituitary gland is a major endocrine organ located at the base of the brain, it is responsible in controlling growth and development and the functioning of the other endocrine glands. The purpose of this research article was to investigate the mechanism underlying the pituitary defects. This was carried out by using different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. OTX2 is a homeo-domain transcription factor that is required for normal head development in mouse and human. Affected individuals exhibit a spectrum of features that range from developmental defects in eye or pituitary development. Mice that expresses Otx2 deficiency in early head development and pituitary oran ectoderm exhibit craniofacial defects and pituitary gland malformation at birth.

The research demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe, and extrinsic effects on anterior pituitary growth. The findings of this research suggest that mechanisms that underlie the diminished hormone secretion by the pituitary gland in patients with Otx2 mutations. The variable ocular, cranio-facial and pituitary defects that arose in Otx2 expression are consistent with the dosage sensitivity for Otx2 in early head development.

 2. Identify the embryonic layers and tissues that contribute to the developing teeth. 

Teeth development is also known as "Odontogenesis", this process commences in week 6 of embryonic development. It involves the ectoderm of the first pharyngeal arch and neural crest, ectomesenchyme.

Embryonic layers and tissues that contribute to the developing teeth:

1. Ameoblast - Epithelial cells that are derived from the oral epithelium of ectoderm and produces teeth enamel. Ameloblasts are the result from preameloblast differentiation which originate from inner enamel epithelium.

2. Odontoblasts - Mesenchymal cells which are derived from the neural crest; depending on their enamel epithelium activity they will differentiate differently. These cells produce predentin which calcifies to dentin which is found beneath the enamel in the crown region and under the cementum in within the root.

3. Periodontal ligament - It provides attachment of the teeth to the alveolar bone of the maxillae and the mandible. The periodontal ligament is composed of fibroblasts, epithelial cells, undifferentiated mesenchymal cells, bone, cementum cells and bundles of collagen fibres.

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

==Lab 9 Assessment - Permalink==

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

User:Z3463514

2015-10-19T06:28:07Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

Lab 10 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:03, 16 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 7 Assessment==
 1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical. 

<pubmed>25315894</pubmed>

The pituitary gland is a major endocrine organ located at the base of the brain, it is responsible in controlling growth and development and the functioning of the other endocrine glands. The purpose of this research article was to investigate the mechanism underlying the pituitary defects. This was carried out by using different cre lines to inactivate Otx2 in early head development and in the prospective anterior and posterior lobes. OTX2 is a homeo-domain transcription factor that is required for normal head development in mouse and human. Affected individuals exhibit a spectrum of features that range from developmental defects in eye or pituitary development. Mice that expresses Otx2 deficiency in early head development and pituitary oran ectoderm exhibit craniofacial defects and pituitary gland malformation at birth.

The research demonstrates that Otx2 expression in the neural ectoderm is important intrinsically for the development of the posterior lobe, and extrinsic effects on anterior pituitary growth.

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

==Lab 9 Assessment - Permalink==

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

User:Z3463514

2015-10-16T02:45:29Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

Lab 10 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:03, 16 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

==Lab 9 Assessment - Permalink==

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

User:Z3463514

2015-10-16T01:03:43Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

Lab 10 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:03, 16 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

User:Z3463514

2015-10-15T12:56:35Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

Talk:2015 Group Project 6

2015-10-15T12:56:23Z

Z3463514:

{{ANAT2341Project2015discussionheader}}

[[Science_Student_Projects]]

[[Abnormal Development - Genetic]]
FISH Image [https://www.genome.gov/images/content/FISH_factsheet.jpg]
associated copyright [https://www.genome.gov/copyright.cfm]
fish data - [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120169/] [http://www.nature.com/scitable/topicpage/fluorescence-in-situ-hybridization-fish-327] [http://www.rarechromo.org/information/Other/FISH%20FTNW.pdf]

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:26, 25 September 2015 (AEST) OK this is such an easy project to find resources for, so where are they? Everyone in research, support groups, genetic inheritance are talking about this topic and the techniques. But this is not on your project page.
Like my comments for the other project pages, animal models and media, graphics, statistics, graphs to support the project information???? Your project is not ready for peer review.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:26, 1 September 2015 (AEST) I would like to see some content (sub-headings) on your project page.

==Peer Reviews==

===1===

I’ll start by saying, you have an extremely extensive list of references. Well done! It shows you have really done your research and made good use of it. Your citations are consistent throughout the page and most paragraphs have multiple sources. I would suggest to perhaps include a hand-drawn image somewhere on the page as well as a video. Aside from the section “biopsy methods”, the page could use a few more illustrations. From what I can see, the image under the subheadings “FISH” and “future/current research”, does not appear to have been added correctly according to the guidelines Mark gave us a few weeks back. There is no caption for the image like there are for the other images.

I really like, how under the “diagnosis” heading, you have made the table of applicable diseases for PGD an expandable table. It helps keep the page clean and easier to control. Perhaps though add a little blurb below the table describing it. You have a great set of heading and subheadings that all relate back to your topic. Given that, you have addressed all important areas pertaining to your topic. May I suggest, that in the introduction section, which I am assuming is yet to be done, you add some epidemiological information and perhaps a video speaking briefly on the topic as it can be quite complex.

Well done on the section titled “future/current research”. It is really useful for students seeking a higher degree of information on this topic as it goes into great detail. However, some direct references in the text to some papers would be good. I also suggest adding a glossary of words to the bottom of the page to cater to those who read the page, with a lower level of embryology knowledge than you or I. In addition to that, it may be good to try and break-down some of your paragraphs as there is a lot of text and it can be hard to take in for some people. Bullet points and tables are great. The page does however, focus well on embryological learning aims.

Lastly, to conclude, I feel a though the table and image under “biopsy method” is a little cluttered and could be spaced out a bit more. Overall, this is a really good and detailed framework and with a little more work will be a great project.

===2===
A very snazzy wiki page so far! You have used a wide variety of images to convey the concepts of prenatal genetic diagnosis to those reading your wiki page. Copyright information and student templates were present for all the images which you provided which is great to see. A hand drawn image is absent, which is a requirement for every wiki page. It might be worth including the hand drawn image in the 'history section' as the information here could easily be represented by a hand drawn flow chart.

I commend you on your inclusion of a 'future/current research' subheading as this gives the reader a perspective of where the field of prenatal genetic diagnosis is heading in the distant future.

I see that you have included a table underneath the 'biopsy methods' subheading. It would be great to see you compile the advantages and disadvantages of blastomere biopsy and trophectoderm biopsy into a tabular format as this would make for an easier reading experience. Furthermore, tables may also be incorporated for the disadvantages and advantages of genetic techniques.
I would recommend the inclusion of other forms of media such as a video or gif to assist in the conveyance of information under certain subheadings. A video/gif would fit nicely underneath the 'biopsy method' subheading, though this is just a suggestion.

Overall your assignment is superb so far. You have successfully covered a vast topic and made successful use of a broad range of sources to support your page. Your inclusion of images has been appropriate, however a hand drawn image is still required.
Keep up the good work guys!

===3===

'''COMMENDATIONS'''

• Good reference list and in text citations throughout.

• Great table of advantages and disadvantages under “Biopsy Methods” (good comparison of the techniques). However, the ‘Blastomere’ row is missing information.

• All key points have been addressed, and it is evident that you have done a lot of research!

'''RECOMMENDATIONS'''

• A short definition at the beginning of your page would help the reader understand what your topic is about. I was a bit unsure as to what ART was when I first began reading.

• Your information could be organised under more subheadings, particularly in your “Polar Body Analysis” section; the information here is quite dense.

• More pictures or animations would be great; make sure you reference your pictures properly as well (the image under FISH is missing a reference).

• More tables – a lot of your information involves advantages and disadvantages. You could create more tables to make the information easier to read/follow. It would also allow you to cut down on details that are repeated, or those that you do not need.

• A self drawn diagram is also missing – maybe this could take the form of a world map and you could label the various countries featured under your “Laws & Legal Status” heading with their respective laws.

It is evident that you have put in a lot of effort into your page. Try and condense the information you have, and add more titles and images to create a more succinct end product. Good job so far!

===4===

This page contains a lot of interesting information regarding the chosen topic, and has been accompanied by some really useful images. I was particularly intrigued by the information you have provided for genetic techniques and hope to see some more images and videos to help your explanation. Especially for PCR, this is a widely used technique for genetic analysis and I am sure there are some really good videos on YouTube you can add to this section. For these procedures, you have also listed a great amount of disadvantages and advantages but it would be easier to read if this were in a table format.

I believe the headings are extremely relevant and cover the correct areas of focus for this topic. However, the use of sub-headings is lacking which makes it difficult for the reader to initially understand the areas that will be discussed on this page. You can easily change the bolded headings under “Indications”, “Preimplantation Genetic Screening”, and “Biopsy Methods” into subheadings with a minor edit. On that note, the table presented in the “Biopsy Methods” is quite confusing as the advantages and disadvantages of “Blastomere” are absent. Also, further elaboration on these headings is needed for the reader to gain an adequate understanding of the topic.

You have provided a really good framework to add more content on this page. This is especially required in your heading of “Diagnosis”. I think a more detailed explanation about how the diseases are linked to PGD is needed to avoid confusion. When I first read it, it didn’t make much sense so perhaps use an image of how these diseases relate to PGD could mend this.

The addition of a “Future/Current Research” heading is very well done. This demonstrates you have thought beyond the mechanics of describing PGD and are looking into extra sources. You may want to consider separating future research from current research to make the page more systematic, and to clearly show what scientists are looking to achieve later. The image in this section is also really good as it is clear and shows the process of extraction. More images, videos or GIFS may be needed to effectively convey the research and procedures to your audience.

Lastly, your reference list is extremely impressive. You have shown you have conducted numerous and successful literature searches and are utilizing them accordingly. An important thing to note is that you are lacking in-text references in a few sections, especially “Biopsy Methods”, and in your lists of advantages and disadvantages. Make sure to add these to avoid academic misconduct to allow your reader to do further reading if they wish.

Overall, this is a really good page so far. You have demonstrated great teamwork and strong efforts to make this page standout. I suggest you consistently edit your work, add more visual aids, and condense your information where possible to gain the mark you deserve. Fantastic work!

===5===

There is no introduction, not having an introduction would mean there is no overview of what this page would be about and what it will discuss in detail. If an introduction could be uploaded maybe consider an image or a short video that would be able to sum the introduction up. This must be done instead of just going straight into the “History “.It would make your page more appealing and professional if you followed through with an introduction. Other than that, I appreciate the detail that went through. There is great amount of reference at the end of each section which is great, however there is no in- text referencing in some sections like procedure of “Genetic Techniques”. Having in-text referencing will allow the audience to know exactly where the information was read from and for the interest of the audience can read that specific paper in detail. There is a great amount of information in almost every section with great detail however, consider more subheadings to make the sections easier to read and allows the audience to navigate the page effortlessly. This was the case for ““Polar Body Analysis” section”. The information here is quite dense therefore you could split or organize information into more subheadings.

I also noticed that there is not enough information in historic findings; this is an important key point that needs to be addressed. Present some online research, add some images, some in text referencing and maybe a table or timeline, this should help shape the historic findings section. Finding information on historic findings might be a little challenging. A suggestion I can make is to search for old articles in PubMed (by adjusting the year). Review articles that summarise historic findings related to Prenatal Genetic Diagnosis may also be helpful. You also need to find information on current research as well. Other subheadings that are either incomplete or missing are “Ethics “and “Future/Current Research”. This can to be done in the same manner as the historic findings. The tables displayed in the other sections are great as they simplify information and is an effective way for students to study so well done! Keep in mind this is meant to be informative and easy to comprehend, so try and find that balance. Thus, consider some more images, diagrams, graphs and tables in each section, to make it more inviting and not overwhelming with just content. Captions should be added on the page for some of the images to state what the images are showing.

Try and look for a youtube video that can help summaries the content on your page. If possible try adding hand drawn images too. A glossary list should be incorporated in a separate subheading to define some of the technical words so that viewers can fully grasp the information.

Having said all those down side points, this page is coming along nicely with many positive aspects:

• Great amount of references at the end

• Concise in text citation except in some paragraphs

• Good use of images

• The use of dot points in different sections to format the info is very useful and provides clarity

• Great table of advantages and disadvantage in section “Biopsy Methods”

• The key points have been clearly described

• Having Future/Current Research” sub heading which is great

Overall, I can appreciate the difficulty of this topic. However if you work on the subheading within each section and add some images, videos and diagrams as well as some in text referencing I think that should make a significant difference by making this page more inviting, easier to navigate and also appear greatly organized. GOOD LUCK

===6===
This project page is very well done. Clearly, you have done huge amount of research on this topic. And all sections of the page are well balanced.

I appreciate that you include the advantages and disadvantages of each diagnostic methods, which not only indicates your thorough understanding of the topic, but also make it easier for readers to compare each methods.

Images and tables are well chosen in your page. It would be great if you can add more visual aids in some sections because there are large amount of texts in some section.

===7===

Your project page is coming along very well so far. You research into the subject seems very extensive and sufficient. You have many citations which have been cited properly. Your long list of references and the many in text citations are evident of the effort and depth that you have gone into your research. Furthermore, you have added a heading on future and current research which further shows the relevance and recent nature of your research beyond the teaching aspect. You have chosen relevant headings and figures so far, explained the key points well and taught the content at a peer level showing a good understanding of the topic. Its great that you have also chosen to include the laws and legal status to show how the topic is relevant to society and how it is being translated from research to the clinic.

While the images you have included so far are engaging and relevant I feel that much more is needed since your research into the topic is very widespread. More images, diagrams and graphs (maybe a graph on the rate of genetic testing use can be helpful) would help to break up the text, balance the page better and make the page more engaging. Also, try to refer to your files in text as well so they may complement your explanations and enhance understanding of the topic. Including your own innovative drawings and searching for relevant videos would also help to teach key points better. When adding your files try to maintain the same formatting, some of your images are added as thumbnails while others are not.

Additionally, you are still lacking an introduction. You have included a heading for it so I assume you will get to it, but make sure its included as its very helpful in orientating your reader and providing some background information for those without a significant scientific background. You should also consider adding a timeline to the section on history, it is more engaging to your viewer and easier to read. I would also recommend adding some more tables, they are visually appealing and also help to break up the text. I suggest you add a table of the diseases tested for, with a brief description of the disease, the specific genetic test used to detect it and at what stage its used. Animal models can also be included to show research into the topic beyond the teaching activities. Finally, make sure you reread over your work and edit your spelling and grammar in some areas.

Good effort overall, well done!

===8===

You have done a great job for your project! As we can see from the amount of your references, huge amount of research must have been done. The key points relating to the topic are clearly described. The page is organized very well and the use of expandable table keeps the page neat. The images and tables used are highly relative to your topic. I would recommend that:

1. Instead of using the acronym, the use of full form ‘Artificial Reproductive Technologies’ for the topic name maybe better.

2. The introductory part is missing. It gives readers an overview of the page and helps readers without background knowledge understanding the topic easier.

3. The layout for the Biopsy Methods part maybe reconsidered. More spacing between three different methods will make the page easier to read. And also, the background color for the table may be lighter. Since the table is a summary of the three methods, I will suggest moving it to the end of the three methods.

4. A hand-drawn image somewhere on the page or a video can be added.

5. For the legal status, it would be nicer if you can classify these countries according to whether they are permit or prohibit.

Overall, you have made a great page. Thanks for your effort.

===9===

This page has an impressive amount of content, this shows that you guys have done amazing research and deducing those which are relevant for this chosen topic. As your page is very content heavy, visual aids (detailed diagrams, videos, tables and flowcharts) can be a great way to lighten the content and keep the audience interested. Remember to add a hand drawn diagram! The heading used were very appropriate for the topic, but the overuse of subheadings makes it harder for the audience to understand. I would suggest to condense some of the subheadings as I think some are not necessary (Laws and Legal Status - it is fine just having the countries in bolding titles) I suggest having them in a table which will look a lot neater. In the subheading, it is clear that there is a lot of advantages and disadvantage; I suggest to have them in table format, making it easier to read for audiences. But it is also good to see that you have made use of bullet points.

Adding a glossary at the bottom will be very beneficial for the audience as there are a few terms that are not explained (IMSI, IVF and FISH etc). There are still a few headings and sub which have not been touched on; “Utilisation of Diseased Cell Lines” and “Ethics” I am certain with more research, no doubt the content of these will be great!

Your reference list is extremely long which is good! Showing you have done numerous and numerous of literature searches and put them to good use. Just to remind you that it is important to have in-site referencing in the body of the page.

Overall, the page was a delight to read! All the content seem to be integrated nicely which shows great teamwork. I am certain after condensing some information and including visual aids, your page will be awesome!

==Discussion==
[[User:Z5088434|Z5088434]]([[User talk:Z5088434|talk]] Would the part you added in indication rather be part of the introduction since it pretty much sums up what the page is about? Maybe go into when PGD and PGS are applied? as for the multiple instances citations: first in text citation has to be like this: <ref name="PMID..."><pubmed>...</pubmed></ref> and the following ones are like this: <ref name="PMID..."/> (just check for the code in the edit mode, can't figure out how to just show the code without it actually configuring it...)
==To Do List==

===Week 4===

*text book summary and some notes

*journal article

*1 relevant media article

*post in this discussion and on your own page under lab 3 assignment

*for links or informal questions please use the facebook Group

==Prenatal Genetic Diagnosis==

===Headings===

* Polar body
* Genetic techniques
* Laws in different countries and states
* Cell extraction from zygotes, blastomeres, morula
* How analysis is conducted e.g. PCR
* Gene Mapping
* Inheritance patterns
* Conducted prior to implantation

In order (?):
* '''Introduction''' (GP)
* '''History/Development (include transition from post to preimplantation)''' (GP)
* '''Indications, Inheritance patterns''' (SL)
** Preimplantation Genetic Diagnosis (PGD)
** Preimplantation Genetic Screening (PGS)
* '''Cell Extraction Methods, side effect''' (SK)
** Polar Body Analysis
** Blastomere biopsy
** Trophectoderm biopsy
* '''Genetic Techniques ''' (GP)
** Fluorescent In Situ Hybridisation (FISH)
** PCR
**Array Comparative Genomic Hybridisation (aCGH)
PMID 26100406 PMID 24771116
**Single Nucleotide Polymorphism

history
explanation
specific examples
application

Next Generation Sequencing
* '''Diagnosis (table, gene mapping)''' (SL)
* '''Utilization of Diseased Cell Lines''' (SK)
* '''Laws/ Legal status''' (SL)
* '''Future/Current Research'''
* '''Ethics'''

==Content==

===Legistation for ARTS===

[https://www.nhmrc.gov.au/health-ethics/ethical-issues/assisted-reproductive-technology-art Assisted Reproductive Technology Ethics]

[https://cbhd.org/content/g12-country-regulations-assisted-reproductive-technologies G12 Country Regulations of Assisted Reproductive Technologies]

==Cell Extraction Methods==
Polar bodies: Applying PGD to polar bodies is desired as it can be used before conception. Since genetic testing can be conducted within twenty four hours this makes it possible for the transfer to the mother at the blastomere stage. However this method isn’t commonly used due to the fact that all oocytes must be tested including those that may not progress to mature and only genetic material from the female can be retrieved <ref name="Coward, K. & Wells, D. (2013). Textbook of Clinical Embryology New York: Cambridge University Press.">Coward, K. & Wells, D. (2013). Textbook of Clinical Embryology New York: Cambridge University Press.</ref>

Cleavage stage: This involves the biopsy of the blastomere (6 to 10 cells) <ref name="PMID11325751"><pubmed>11325751</pubmed></ref>. It is advantageous to work on blastomeres as they are totipotent, meaning they can give rise to a diverse range of cells. Studies have also shown that there is no increase in congenital abnormality rates caused by the removal of blastomere cells <ref name="Coward, K. & Wells, D. (2013). Textbook of Clinical Embryology New York: Cambridge University Press."/>. Contrarily, studies have shown that the standard removal of two blastomeres at one time will decrease its potential to develop into a blastocyst <ref name="PMID19773223"><pubmed>19773223</pubmed></ref>. Along with the fragility of the cells at this stage, highly skilled embryologists are required to minimise poorly performed biopsies which could subsequently lead to impaired growth and a decrease in implantation. Unlike polar bodies both maternal and paternal genes can be tested if PGD is performed at this stage. <ref name="Coward, K. & Wells, D. (2013). Textbook of Clinical Embryology New York: Cambridge University Press."/>

Blastocyst: Performing PGD at this stage is the least common since many patients do not produce embryos healthy enough to reach this stage. Multiple cells can be extracted at this stage for biopsy producing more accurate results. This is possible due to the fact that biopsies have little effect on the development of the embryo. Genetic tests must also be conducted rapidly since implantation is optimal at this stage <ref name="Coward, K. & Wells, D. (2013). Textbook of Clinical Embryology New York: Cambridge University Press."/>

==Textbooks==

===The Developing Human 9th Edition: Birth Defects caused by Genetic factors===
<ref> Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2011). The developing human: clinically oriented embryology (9th ed.). Philadelphia: Saunders.</ref>

* Estimated to cause one third of all defects
* Abnormalities in chromosomes are usually due to structural or numerical changes. These can occur in sex chromosomes or autosomes.
** Numerical abnormalities are a result of nondisjunction. Nondisjunction is when a pair or chromatids fail to disjoin during meiosis or mitosis. E.g. Turners Syndrome, Trisomy 21 (Down syndrome) and Trisomy 18 (Edward’s Syndrome).
** Structural abnormalities are usually a result of chromosome breakage followed by reconstitution in an abnormal combination. There are different types of structural abnormalities including translocation and deletion of chromosomes
* Mutations cause 8% of birth defects. It involves the loss or change in the function of a gene which is permanent and heritable.

===Williams Obstetrics, Twenty-Fourth Edition: Preimplantation Genetic Testing===

<ref> Cunningham F, Leveno K.J., Bloom S.L., Spong C.Y., Dashe J.S., Hoffman B.L., Casey B.M., Sheffield J.S. (2013). Prenatal Diagnosis. In Cunningham F, Leveno K.J., Bloom S.L., Spong C.Y., Dashe J.S., Hoffman B.L., Casey B.M., Sheffield J.S. (Eds), Williams Obstetrics, Twenty-Fourth Edition. Retrieved August 25, 2015 from {http://accessmedicine.mhmedical.com/content.aspx?bookid=1057&Sectionid=59789152.} </ref>

* two categories of preimplantation genetic testing: PGS (-Screening) & PGD (-Diagnosis); different indications
** PGS: IVF procedure due to infertility without known genetic abnormalities in patients
** PGD: IVF procedure & genetic testing chosen because of known genetic abnormalities in patients
* Methods:
** Polar body analysis: first and second polar body are extruded following completion of meiosis I and meiosis II
*** Advantages: does not harm embryo, can be used to detect 146 Mendelian disorders, reported 99% accuracy
*** Disadvantages: paternal genetic contribution is not investigated --> additional procedures
** Blastomere biopsy: embryo is 3 day old, 6-8 cells stage, most commonly used, hole is made in zona pellucida to retrieve one cell
*** Disadvantages: 10% pregnancy reduction,"mosaicism of the blastomeres may not reflect the chromosomal complement of the developing embryo"
** Trophectoderm biopsy: 5-6 day old blastocyst, 5-7 cells are removed
*** Advantage: no cells removed from embryo
*** Disadvantage: additional procedures may be necessary because of later stage of developing embryo (cryopreservation, implantation at later IVF-cycle)

===Maternal, Fetal & Neonatal physiology: a Clinical perspective :Prenatal Diagnosis and Maternal, Fetal & Neonatal physiology: a Clinical perspective: Prenatal Diagnosis:===

Prenatal diagnosis is the screening process that tests an early fetus for overall growth, complications of pregnancy, birth defects and chromosomal or genetic abnormalities within the first 2 trimesters. It aims to provide the parents with as information as possible to help them make an informed decision about the infants quality of life. In 90-95% of the cases negative outcomes occur; confirming the healthy state of the fetus, should a genetic abnormality be present, it provides the parents with the opportunity to investigate further with other tests, and possible fetal therapeutic treatments available as well plan and prepare for the disabled infant or to terminate the pregnancy.

*Indicators for prenatal screening/ high risk factors include:
**maternal ages > 35 years
**paternal ages > 50-55
**history of 2+ miscarriages
**previous pregnancy or family history of a preexisting genetic or chromosomal disorder
**suspected carriers of genetic disorders
** maternal disease/condition present (high BP, diabetes)
**abnormal ultrasound or serum test results within the first 2 trimesters
**family history of neural tube or other birth defects

*Ultrasonography:
**high frequency sound waves are used to generate a image of the fetus
**relatively non-invasion; its conducted transabdominally or transvaginally ( producing a higher resolution image)
**It reveals the presence/absence of congenital abnormalities, characteristics of fetal growth and development, uterine development status; amount of **amniotic fluid, placental position, umbilical blood flow and the presence of multiple gestation.
**(if abnormalities are detected further testing is recommended)

*Amniotic Fluid Analysis/:
**samples are obtained through amniocentesis
**the amniotic fluid is analyzed for its biochemical composition
**earlier in the pregnancy it can be examined for sex determination and to diagnose genetic or chromosomal disorders present.
**Later into the pregnancy it provides an indication of fetal maturity and well being
**Feta; cells recovered from the amniotic fluid can be cultured for specific karyotypes, to test for Chromosomal Abnormalities, and analysed for Alpha- fetoprotein (AFP) a biochemical marker of metabolic disorders and neural tube defects as well as other abnormalities.
**Amniocentesis- occurs usually between weeks 14-20 as amniotic fluid has reached the optimal volume (150-250mls) allowing 20-30mls to be removed with a relatively low risk or fetal or maternal complication, and in time for a 2nd trimester abortion.
**early amniocentesis ( before week 13) increase the risk of fetal loss, leakage of essential amniotic fluid and talipes equinovarus.

*Chronic Villus Sampling (CVS):
**occurs roughly 10-13 weeks after last menstrual cycle, ensuing a sufficiently developed chorionic villi but before the chorion laeve forms the definitive placenta.
**ultrasounds is used to locate the gestational sac and implantation then a transcervial or transabdominal approach is used to aspirate living tropoblast tissue.
**sample is analyzed for chromosomal abnormalities or with enzyme assay.
**advantages: earlier diagnosis , decreased waiting period
**disadvantages: risk of spontaneous abortion, bacterial infection, bleeding, leakage of amniotic fluid, inability to diagnose neural tube defects this early, early cleavage (before wk 10) is associated with increased risk of limb defects (due to insufficiently developed chronic villi)

*Umbilical Blood Sampling:
**can occur as early as 16 weeks
**using the umbilical cord to obtain fetal blood samples - with real time ultrasound
**used to diagnose inherited blood disorders, to detect congenital infections, to assess fetal anemia and in treatments such as blood transfusions.
**disadvantages: risks of infection, preterm labor, thrombosis, bleeding & transient fetal arrhythmia

*Fluroscent in Situ Hybridisation (FISH)
**rapidly detects (within 24 hours of testing ) the presence of Trisomies 21, 13 and 8 and alterations in sex chromosomes in uncultured cells.

*early diagnosis allows the opportunity for intervention with fetal therapies:
**surgical intervention urinary tract obstruction ; aiming to reduce prenatal renal damage
**fetal transfusions ( feta anemia
**fetal medical treatmetn ( fetal cardiac arrhythmias,impaired thyroid function etc.) treatment occurs usually through the mother
** infusions for hematologic conditions
**stem cell transplantation
**gene therapy
**pharmocolic interventions

textbooks used :

*Maternal, Fetal & Neonatal physiology: a Clinical perspective <ref> Blackburn, S.L. (2003) '''Maternal, Fetal & Neonatal physiology: a Clinical perspective''' (2nd ed.). Seattle: Saudners </ref>

*Langman's Medical Embryology (12th ed.)Chapter 9, pages 125-129 <ref> Sadler T.W.(2012) '''Langman's Medical Embryology''' (12th ed.)
Philadelphia: Lipincott, Wiliams & Wilkins, a Wolters Kluwer Business </ref>

the following are two articles about a newly available and accessible prenatal non- invasive genetic test- Blood sampling:

*Report on Cutting edge prenatal screening technology to become available in Australia <ref> Carbonell, R. Shinners, A. Amor, D. Mark, D. (2015) '''Report on Cutting edge prenatal screening technology to become available in Australia:''' ''Prepared for ABC news, PM with Mark Colvin.'' Retrieved from {http://www.abc.net.au/pm/content/2015/s4203200.htm} </ref>

*Blood Test takes risk out of prenatal testing <ref> Begley, S. (05/07/2015) '''Blood Test takes risk out of prenatal testing'''. ''ABC Science.'' Retrieved from
{http://www.abc.net.au/science/articles/2012/07/05/3539549.htm} </ref>

* Prenatal screening and Diagnostic Tests Information Pamphlet <ref> Western Australia. Department of Health Genetics Council Prenatal Diagnosis Committee (2011)'''Prenatal screening and Diagnostic Tests'''. Retrieved from {http://www.health.wa.gov.au/docreg/Education/Prevention/Genetics/HP3131_prenatal.pdf} </ref>

==Articles==

<pubmed>24810687</pubmed>

<pubmed>23773313</pubmed>

<pubmed>26201722</pubmed>

<pubmed>26168107</pubmed>
''This article reviews the cytogenetic techniques and embryo biopsies required for PGD & PGS and gives an account on the differences in PGD for single gene defects and chromosomal translocations.''

<pubmed>22723007</pubmed>
''This article gives relatively recent and detailed information on the three types of biopsy performed on embryos at different stages of development (before conception, after fertilization, and early cleavage or blastocyst stage)''

<pubmed>24515905</pubmed>
''This article reviews indications for PGD focusing on single gene disorders.''

<pubmed>20966459</pubmed>
''This article gives detailed laboratory instructions and guidelines for PGD procedures, which might be useful for the methodological part of the website''

''The following articles are about diseased cells/embryos derived from PGD procedures for further research:''
<pubmed>23242925</pubmed>
<pubmed>22735930</pubmed>

''Other articles''
<pubmed>21748341</pubmed>

<pubmed>26259216</pubmed>

<pubmed>26258137</pubmed>

<pubmed>22404048</pubmed>

<pubmed>26238130</pubmed>

<pubmed>26168107</pubmed>

IVF and prenatal genetic testing in Australia
[[http://virtushealth.com.au/australian-first-new-genetic-testing-set-improve-access-and-outcomes-ivf-patients]]

the following are two articles about a newly available and accessible prenatal non- invasive genetic test- Blood sampling:
[[http://www.abc.net.au/pm/content/2015/s4203200.htm]]
[[http://www.abc.net.au/science/articles/2012/07/05/3539549.htm]]

User:Z3463514

2015-10-15T12:28:43Z

Z3463514:

==Lab Attendance==
Lab 1 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:45, 7 August 2015 (AEST)

Lab 2 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 13:21, 14 August 2015 (AEST)

Lab 3 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:28, 21 August 2015 (AEST)

Lab 4 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:12, 28 August 2015 (AEST)

Lab 5 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:13, 4 September 2015 (AEST)

Lab 6 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:21, 11 September 2015 (AEST)

Lab 7 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:08, 18 September 2015 (AEST)

Lab 8 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:04, 25 September 2015 (AEST)

Lab 9 --[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 12:07, 9 October 2015 (AEDT)

==Lab 1 Assessment==
Article 1 PMID 26131222

The aim of this article was to determine the impact of oxygen concentration during in vitro culture of human oocytes and embryo on fertilisation, implantation, pregnancy, gestation and abortion rates. Women between 20-48 years old who are seeking for infertility treatments and intracytoplasmic sperm injection participated in this experiment. Embryos were randomly allocated for incubation under three different oxygen conditions, the first group was subjected to 20% Oxygen in air. The second group was initially subjected to 20% Oxygen in air, then on the following day (day 2) 5% Carbon Dioxide and 90% Nitrogen gas was introduced into the system while Oxygen was decreased to 5%. Finally, the third group was subjected to 5% Carbon Dioxide gas and 90% Nitrogen gas throughout the experiment.

To determine its ability to yield a successful pregnancy, the embryo must be cultured and incubated for 2-6 days in a defined medium.

Embryos cultured in 5% Oxygen in air presented highest rates of fertilization and implantation compared to those incubated in 20% Oxygen in air. Meanwhile, embryos cultured in 20% Oxygen in air also presented high rates of fertilisation, high quality embryo and implantation. Intracytoplasmic sperm injection derived embryos cultured in 20% Oxygen in air resulted in lower rates of cleavage compared to those of from the second group, from 20% - 5% Oxygen in air. These results were consistent with the data previously published.<ref><pubmed>25131222</pubmed></ref>

 Article 2 PMID 26238449

The objective of this article was to evaluate in vitro maturation, IVM in sub-fertile women with polycystic ovarian syndrome undergoing IVF, by comparing outcomes with a control group of non-polycystic ovarian syndrome women. IVM involves the in vitro culture of immature oocytes from metaphase II, when the oocyte is considered to be fully mature to undergo fertilisation. This could be a groundbreaking procedure for women suffering polycystic ovarian syndrome as these gametes has expressed their maturational and developmental competence after their retrieval from the ovaries.

A total of 268 patients suffering with polycystic ovarian syndrome, 100 PCO patients and 400 controls were included in the investigation. The analysis provided information suggesting that IVM is a preferable approach in treating women with PCOS during an IVF cycle compared to those without the syndrome. Thus is was concluded that IVM was more efficient as a treatment option in terms of clinical pregnancy, implantation and cycle cancellation rate in women suffering PCOS. <ref><pubmed>26238449</pubmed></ref>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) Good summaries of these 2 articles. The second article is particularly interesting. (5/5)

==Lab 2 Assessment - Images==

{{Uploading Images in 5 Easy Steps table}}

[[File:Deer mice oocytes at various stages of development in vitro.jpg]]

Deer mice oocytes at various stages of development in vitro <ref><pubmed>23457518</pubmed>| [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0056158]</ref>

PMID 23457518

Copyright: © 2013 Choi, He. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:46, 16 September 2015 (AEST) You have uploaded the image OK and given it a suitable name. You have not included the reference, copyright and student template in the image summery box (copyright not required on your page here). I have updated your image summary box for you to demonstrate how this information should appear with uploaded images. (3/5)

==Lab 3 Assessment==

1. Shiraishi, K., Ohmi, C., Shimabukuro, T., & Matsuyama, H. (2012). Human chorionic gonadotrophin treatment prior to microdissection testicular sperm extraction in non-obstructive azoospermia. Human reproduction, 27(2), 331-339. PMID 22128297

2. Irvine, D. S. (1998). Epidemiology and aetiology of male infertility. Human Reproduction, 13(suppl 1), 33-44. PMID 9663768

3. Lotti, F., & Maggi, M. (2015). Ultrasound of the male genital tract in relation to male reproductive health. Human reproduction update, 21(1), 56-83. PMID 25038770

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) These references relate to your group project work. You could have used the reference template here and perhaps given a sentence explaining the relevance to the topic. (5/5)
==Lab 4 Assessment - Quiz Questions==

 Early Vascular Development 

<quiz display=simple>

{Which of the following statement is correct about angiogenesis:
|type="()"}
- Begins week in extra embryonic mesoderm and then embryonic splanchnic mesoderm
- Begins as the formation of blood islands
- Blood islands extend and fuse together to form a primordial vascular network
- VEGF and PGF stimulates growth and development
+ All of the above
||Yes, angiogenesis is a vital process in growth and development as well as in wound healing as it is the physiological process for the formation of new blood vessels from existing vessels.

{Which of the following statement is NOT correct about blood vessel remodelling:
|type="()"}
- The branches from main arteries may arise as new outgrowths from the enlarged stem
- VEGF is required later for endothelial cell maintenance in tissues
- Extensive remodelling during embryo development leads to an asymmetrical adult system in the body
+ Early vascular development is asymmetrical
||During early vascular development it is laterally symmetrical.

{What cells are not contained in blood islands?
|type="()"}
+ Blastocyst
- Harmoangioblasts
- Angioblasts
- Haemocytoblasts
||Blood island contains haemangioblasts which have the ability to differentiate into angioblasts and harmocytoblasts which are vascular and blood cell precursors respectively.

</quiz>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:50, 16 September 2015 (AEST) Q1 does not really test the students knowledge on the topic and your explanation in the answer also does not help those who may have gotten the question incorrect. You need to have gone through each option with an explanation here as well as perhaps links to useful resources. Q2 "NOT correct" type of questions are always difficult to design correctly without just "tricking" the student. In particular your third option basically sets up option 4 as the only correct answer. Once again more work on your revealed answer required. Q3 is really a very silly question and does not test an embryology student. (7/10)

==Lab 5 Assessment==

 What is the difference between gastroschisis and omphalocele? 

Gastroschisis and omphalocele are congenital abnormalities of the abdominal wall and are the most common anterior abdominal wall abnormality in infants. Gastrochisis is a congenital malformation which occurs in the abdominal wall due to incomplete closure of the lateral folds during the initial gestation. Unlike omphalocele, the exposed viscera lateral, usually to the right, to the closed umbilical ring does not have a covering sac or remnant membrane.<ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> Through thorough research, it appeared that the gastroschisis could be the result of amniotic damage, poor prenatal care, maternal infections and younger maternal age. <ref>Bargy, F., & Beaudoin, S. (2014). Comprehensive Developmental Mechanisms in Gastroschisis. Fetal diagnosis and therapy, 36(3), 142-149.
PMID25171094</ref>

Omphalocele is a congenital defect which is thought to occur during the process of body folding. It is where the umbilical cord and intestinal tract are extruded or herniated through the umbilical ring with a covering sac or sometimes with its remnants of peritoneum and amnion. Research has observed that the formation of an omphalocele is highly associated with chromosome abnormalities such as trisomies 18 and 13. The clinical discrepancy between the two malformations were based upon its location, size and whether the covering sac or remnant is present or absent. <ref>Calzolari, E., Bianchi, F., Dolk, H., & Milan, M. (1995). Omphalocele and gastroschisis in Europe: a survey of 3 million births 1980–1990. American journal of medical genetics, 58(2), 187-194.</ref> <ref>Júnior, E. A., Rolo, L. C., Tonni, G., Haeri, S., & Ruano, R. (2015). Assessment of fetal malformations in the first trimester of pregnancy by three-dimensional ultrasonography in the rendering mode. Pictorial essay. Medical ultrasonography, 17(1), 109. PMID 25745664</ref> It was observed that infants with omphalocele were more susceptible to have other anomalies, and were diagnosed with pulmonary hypertension. <ref>Corey, K. M., Hornik, C. P., Laughon, M. M., McHutchison, K., Clark, R. H., & Smith, P. B. (2014). Frequency of anomalies and hospital outcomes in infants with gastroschisis and omphalocele. Early human development, 90(8), 421-424.
PMID 24951080</ref>

During the first trimester, vaginal ultrasound may be able to diagnose whether a foetus of as early as 12 weeks suffers from gastrochisis and omphalocele. The ultrasound may assist paediatric surgeons to identify the contents of the herniation and malformation.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:00, 16 September 2015 (AEST) Correct. (5/5)

==Lab 8 Assessment - Peer Assessment==
 Group Project 1 

It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

 Group Project 2 

This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

 Group Project 3 

Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

 Group Project 5 

This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

 Group Project 6 

[[Test Student 2015]]

==References==

<references/>

{{StudentPage2015}}

Talk:2015 Group Project 5

2015-10-15T12:28:14Z

Z3463514:

{{ANAT2341Project2015discussionheader}}

Hey guys - i tried to upload a video for the how cancer cells work section - but i have no idea how to do it, tried looking it up but have failed immensely! so i you know how to do it - please explain haha so grateful! thanks --[[User:Z5015534|Z5015534]] ([[User talk:Z5015534|talk]]) 12:42, 4 October 2015 (AEDT)

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:23, 25 September 2015 (AEST) OK, there is so much more that should be on your project page by now. That currently consists of all text, no media, histology, graphics, tables etc. Furthermore no discussion of animal models used in research for this topic. This project page is not ready for peer review.

Hi everyone,
the page is coming together well.
only thing is while we write up our parts can we focus on all using in text referencing so that we are consistent and can just have a single reference list at the bottom.
I found out how to use the same reference again and only have it associated with one in text number, so if you are using the same reference and would like me to show you how to do this let me know :)
--[[User:Z3463667|Z3463667]] ([[User talk:Z3463667|talk]]) 21:40, 14 September 2015 (AEST)

I have added some of the references + citations but not yet finished as this is only the draft and I might delete some of the parts so there is no point adding the citations/ text referencing now. I will add my part at the end. I'm still waiting for your part to see what to do. http://www.ncbi.nlm.nih.gov/pubmed/15951668
--[[User:Z3463890|Z3463890]] ([[User talk:Z3463890|talk]]) 08:35, 17 September 2015 (AEST)

=Research/Review articles=

===[Oncofertility and breast cancer: Where have we come from, where are we going?].===

<pubmed>25991386</pubmed>

This article focuses on the current context of national and international recommendations, techniques development to evaluate and preserve fertility and patients' claims, this study aims to make a survey about the management of patients' breast cancer regarding oncofertility. This article concludes that , in order to satisfy patients' requests, several improvements have to be made regarding the patients' information, the health professionals' awareness and care coordination.I don't go through it now but very interesting article to read and useful for our group project.

===Emergency fertility preservation for female patients with cancer: clinical perspectives.===

<pubmed>26026071</pubmed>

This article explains about clinical perspectives to explore the new as well as the currently available options and strategies that can be used for emergency fertility preservation of female cancer patients.Such options include emergency ovarian stimulation, embryo freezing, egg freezing, ovarian tissue freezing and autotransplantation, in vitro maturation, and ovarian protection techniques. This article also mentions the advantages and disadvantages of each option as well as a new comprehensive multi-step strategy for these situations.

===Sexual dysfunction and infertility as late effects of cancer treatment===

<pubmed>26217165</pubmed>

As all we know, Sexual dysfunction is the main consequence of cancer treatment. Problems are usually linked to damage to nerves, blood vessels, and hormones that underlie normal sexual function. This article emphasizes on these sexual dysfunction and does in depth. It addresses that innovations in cancer treatment such as robotic surgery or more targeted radiation therapy have not had the anticipated result of reducing sexual dysfunction. Therefore, advances in both technologies and in knowledge about how cancer treatments can damage fertility, offer hope to patients who want children.

===Impact of fertility preservation counseling and treatment on psychological outcomes among women with cancer: A systematic review===

<pubmed>26264701</pubmed>

This article explains about psychological outcomes in female cancer patients who undergo fertility preservation counseling/consultation (FPC), with or without fertility preservation (FP).I read through the whole article as I found it really interesting and relevant to our group project. This is another subheadings we can add to those.

--[[User:Z3463890|Z3463890]] ([[User talk:Z3463890|talk]]) 11:24, 24 August 2015 (AEST)

I DID THE SAME :)

===Variability in the practice of fertility preservation for patients with cancer.===
<pubmed>26010087</pubmed>
This is an interesting article on how reproductive endocrinologists counselled cancer patients on fertility preservation. This is relevant to our group projects because it gives us an idea of what techniques and services are currently being utilised to help women.

===Strategies for fertility preservation in young patients with cancer: a comprehensive approach.===
<pubmed>24669162</pubmed>
This article recognises that as cancer treatment improves the life span of patients, with it comes the treat to fertility. It is a great article as it clearly states what methods are currently available for addressing fertility preservation in males and females.

===Clinical guide to fertility preservation in hematopoietic cell transplant recipients.===
<pubmed>24419521</pubmed>
This article focuses specifically on patients suffering infertility due to hematopoietic cell transplantation. It lists the options available to the patients whether female or male, which are applicable to patients who underwent other treatments and also lists the barriers to fertility preservation.

===Fertility preservation in patients with haematological disorders: a retrospective cohort study.===
<pubmed>24140311</pubmed>
This article addresses fertility treatment in patients with haematological disorders specifically. However, is it a really good article as it is a cohort study comparing patients at various stages in their cancer journey, such as those who have had prior chemotherapy, those who pursued ovarian stimulation and those who did not pursue fertility treatment at all.

just moving my articles here for reference while i edit the project page.
--[[User:Z3463667|Z3463667]] ([[User talk:Z3463667|talk]]) 11:39, 14 September 2015 (AEST)

Hi
I have added some points to the page but i will add more info soon. In terms of references and accurate citation, I have written down all the references and I will add those at the end as I might edit/delete some of them. I will explain those fertility drugs too. just added the names and do them over weekend.

--[[User:Z3463890|Z3463890]] ([[User talk:Z3463890|talk]]) 08:58, 11 September 2015 (AEST)

Hi everyone,

yes, I agree we have to assign everyone a certain section to write about, I'm happy to do Infertility causing cancers ( I already found those related articles from pubmed) and Oncofertility timeline. so if everyone is happy I can start it :)

--[[User:Z3463890|Z3463890]] ([[User talk:Z3463890|talk]]) 08:05, 27 August 2015 (AEST)

Hi People,

Does anyone know how to reference a non pubmed source? I'm not sure how to reference the general information that we want to put on our page?
I definitely think also that we should assign everyone a certain section to cover - so that were not all just editing and adding stuff in chaos - Ive started editing the chemotherapy section of the page - i hope this is alright if i take that on- i found some good info! dont worry the stuff i have up now is no where near finished.. just having a play around with general stuff and trying to get the hang of editing etc... (literally no nothing about IT...) But at the end it obviously will be all sorted and good :)

Thanks

--[[User:Z5015534|Z5015534]] ([[User talk:Z5015534|talk]]) 16:18, 26 August 2015 (AEST)

Hey everyone,

As discussed we will be researching oncofertility as our topic for this week, and depending on how successful our research is we will decide on whether we stick to the topic or not.
I have added some potential subheadings to help guide our research, feel free to change them and add more.
We need to pick a subheading each and find research articles related to it for this weeks individual lab assessment.
https://oncofertility.northwestern.edu/patients/fertility-preservation-options-nu --> this is a good website to trigger ideas to research.
--[[User:Z3463667|Z3463667]] ([[User talk:Z3463667|talk]]) 17:12, 23 August 2015 (AEST)

==Peer Review===

===1===

Let me start off by commending this group on a fantastic page! It is incredibly thorough, detailed and long. You can immediately see that a lot of work and research has gone into it. You have a great list of references and they appear to be cited correctly throughout the page. However, some sections which appear to be incomplete and lack some citations e.g. “fertility preservation”.

One suggestion I will make, is it would be good to see the addition of some hand-drawn images, perhaps one under either of the first 3 headings. Some more images could be used under the heading “surgery”. The videos used on this page are great. Really informative, relevant and easy to watch. I also think the “what are cancer cells” section should be higher up on the page as it is part of the basis of what the whole page is about. It also cuts between the two sections “chemotherapy” and “how does chemotherapy work?” which should be one after another. On the topic of formatting, you have a heading in there called “oncofertility timeline”, I think it would be better placed at the beginning of the page where it is more relevant.

I also think there is just too much text in some areas e.g. “Fertility preservation in women” and “surgery”. It makes that part of the page look clustered and difficult to read. Perhaps simplifying it more into bullet points, as you have done in other areas of the page, would be good. Conversely though, I think areas such as “targeted drugs” and “bone marrow or stem cells transplant” could use more work, however, it is possible you still intend to work on those areas anyway.

I would suggest adding a glossary to the bottom of your page to assist in those who view your page with a lower level of scientific knowledge. You have covered an expansive range of topics pertaining to your topic, all of which are relevant and link well with each other. The page has a great focus on the learning aims of embryology. I think with some formatting corrections and some simplification of the text, this will be a really wonderful page.

----
Awesome page so far guys! I commend you on your use of various videos to assist in conveying your ideas. Furthermore, the images you have chosen are highly relevant to the topic of discussion and assist the reader in gaining a greater understanding of oncofertility. All copyright information is present for the images you have used which is excellent to see.
It may be worth including a hand drawn image under the 'radiation' subheading, as we are required to include at least one such image. The current image under the radiation subheading could easily be replicated by hand and could fulfill this portion of the criteria.

I am nitpicking here, but I would also recommend including some kind of media, most likely a picture, underneath the surgery subheading. It might even be worth doing the hand drawn image here if possible. A picture may also be good underneath the 'types of chemotherapy drugs' subheading, just to break up the wall of text and improve the reading experience for the reader.
It might also be worth restructuring the 'oncofertility limitations' subheading into the form of a table (if possible), as the bullet point format feels quite awkward and out of place compared to the rest of the page.
The inclusion of a glossary is also recommended, as this page will be accessible by the general public and a glossary will assist those without a background in embryology to understand and appreciate your content.

Keep up the great work guys! Your page is absolutely amazing so far and the effort you have put in is definitely reflected in the high quality of your page.

===3===

'''COMMENDATIONS'''

• The short video was a good visual aid that helped me understand your topic.

• The use of tables and a few images were good additions to your page.

• Good referencing throughout.

• Your “Oncofertility Timeline” was great; straight to the point and well organised. Maybe place it at the beginning of your page as a part of your introduction?

'''RECOMMENDATIONS'''

• Make sure your proofread your work; I saw a few very long sentences that could be broken up into smaller sentences. This will make your page easier to read and understand.

• Furthermore, some words are capitalised that don’t need to be; e.g. “Oncofertility” in your introduction and “Chemotherapy” in the Infertility section.

• Your page would benefit from the use of subheadings. There are large chunks of information under your headings, making it a bit difficult to follow at times (particularly in your Radiation section).

• I recommend reading through your information and removing details that may be excessive. By making your information more concise, your page will flow better and will encourage the audience to keep reading. Some of the information is a bit repetitive across your sections.

• I liked the use of a table in “Fertility Preservation in Men,” however, I feel as though you could add more details to it. I found the concepts presented in this table difficult to understand; maybe link it a bit better to the information below? Or just organise all of the information into a table?

Very well researched topic, with all key points being addressed. Condensing all of your research and being a little more selective about what you include will be the key to a great final page.

===4===

The wikipage looks like it’s progressing very well, especially with the amount of content and references I can safely say you guys have worked hard on it and have done a substantial amount of research so well done guys. I liked the flow chart that you guys inserted, it really simplified the understanding of the IVF procedure as opposed to reading lengthy text. I also particularly liked the collapsible timeline which was presented very nicely and summarised the progress of oncofertility over time very well.

As for improvements, the references definitely need to be fixed up. There were multiple appearances of the same reference and some of the links also did not work such as reference 24 and 25. On top of that the referencing for the websites were not in a consistent format and some were also done incorrectly so be sure to fix that up. I would also look out for the type of sources used such as webmd and medianews today. I’m not entirely sure if they are reliable or acceptable but I suggest you consult Mark about that.

Additionally, the use of tables is a very good way of presenting information however, for the tables under the topic of fertility preservation for both men and women I initially though that each of the columns was a comparison against each other. Only later did I realise that each of the columns contained an individual list of treatments. To minimise the confusion I suggest rearranging the table and labelling row 1 as ‘Before treatment’, then row 2 as ‘During treatment’ and finally row 3 as ‘After treatment’ then collectively placing the treatments in their rightful spaces in the following column.

A glossary is also missing from this page, having the definitions of the more difficult terms would assist with understanding the topic. Also on another note in the ‘Types of Chemotherapy drugs’ section, I think it would look more aesthetically pleasing if bullet points were used rather than the dashes.

Overall, there is a substantial amount of content, and great use of images, videos and tables. Keep up the good work!

===5===

This page is progressing really well. You have lots of content aided by some videos and relevant images. You have discussed extremely relevant aspects of your chosen topic, which is highly commendable, however the page seems very content heavy. I would suggest making the bolded headings as actual subheadings to make it easier for the reader to ‘jump’ sections. This is evident for sections “Surgery”, “Fertility Drugs”, and “Fertility Preservation in Men and Women”. To break up the text further and keep the page exciting for your audience, consider using bullet points to convey your information under the sections previously mentioned. You have used dashes (-) but perhaps the different colour and layout of the bullet points will make your page much neater.
I should also note that the oncofertility timeline has been condensed well. You may want to move it to the top of the page for readers to understand the history of oncofertility and its progression.

The videos you have incorporated are very insightful and easy to understand. The same can be said for the images on the page as they help to explain the information you have laid out. The only exception I have is for the images under “Radiation” and “Chemotherapy”. Although they are relevant and simple, you may want to replace them for a diagram or flow chart that is more practical to the reader. For example, you could draw a diagram or flow chart of how radiation and chemotherapy eliminate cancer cells. Because you have a lot of text, try adding more images, videos, or condensing the information into a table, especially in “Surgery”, “Types of Chemotherapy Drugs” and “Fertility Preservation”.

Throughout the page, there are areas that have not been focused on as much as others. This includes “Artificial Insemination” and “In-Vitro Fertilisation” where there is very little content. These processes are currently really big in the fertility industry so with more research, I am certain there will be relevant articles to use for your page. You could also refer to these studies specifically to support the content, and discuss their success rates.

The references have been cited inconsistently, which can be fixed with proofreading. In particular, references 19 to 25, 33 and 44 needs to be checked as they have been incorrectly cited or are non-existent. I am also finding that content under a few sections are lacking in-text references, such as “Radiation”, “How Does Chemotherapy Work?”, “Types of Chemotherapy Drugs” and “Side Effects”. Be sure to add citations in these headings to avoid being accused of plagiarism, and to encourage further reading by your readers.

So far this page is very impressive. The amount of information you have included, and the useful videos shown, demonstrates your hard work and efforts into making this page successful. With more editing, visual aids and content, this page will be tremendous. Well done!

===6===

This is an excellent group project wiki. The content covers the topic in all aspects. However, there might be excessive effort in the investigation of ‘infertility’, ’Fertility Drugs’ and ‘Chemotherapy’, which occupied more than half of your project page. They are relevant to this topic, but might need to be consolidated to balance the page.

Images and videos are good choice in your page. It would be better if more images, diagrams, tables are added into your page to balance the texts.

Referencing and citing are excellent in most section, although some sections seem to be lack of in-text references. You might still want to work on them.
Overall, this wiki is an excellent work in investigating oncofertility. It is relevant to the aim of learning embryology.

===7===

Awesome page overall guys- I think everyone has agreed that it is an amazing achievement and you have done a great job.

The amount of research and the number of resources; as well as the correctly referenced sources, is something the be very proud of. It also presents a very thorough and detailed explanation about the topic that creates a well rounded and highly informative page. I also really liked the inclusion of bolded subheadings under the "Surgery" section as it made the page easier to read; however there seems to be a little bit of inconsistency as later in the page seemingly random words are in bold text- I wasn't sure of their importance or whether you were going to include a glossary so I got a little side tracked and I found that section a bit more difficult to read.

A few areas of improvement-- there aren't many; especially to do with the actual writing and information of this page. The first would be to include some more images, videos, tables or diagrams. Although you have quite a few already, the sheer size of the page and the amounts of information beneath each subheading means that you really do need to have more interactive elements and visual aids to help with understanding the content; I found that sometimes I got a little lost within the large chunks or writing and it became more difficult to follow. There seems to be a little bit of inconsistency throughout the page and because there are such vast amounts of information beneath most subheadings, I think that it would be beneficial to restructure some of the sub headings such as "Bone marrow or stem cell transplants" into sub-sub-headings to aid with continuity and over all visual aesthetics of the page. Finally, another way to reduce to presence of chunks of information would be to utilise some more tables to break up the volume and density of information, especially because it is a very heavy (terminology wise) topic.

Over all you guys have done an absolutely outstanding job and I really look forward to the final product!! Good Luck!!

===8===
This page is off to a really good start! Just skimming through the page shows that you have really done thorough research. The page is very content heavy but it is also good to see that you guys have began to add detailed images, tables and videos. To make the page seem less content heavy, I suggest changing some bolded heading to Subheading which will neatly and evenly space out the content; it will make it easier for the audience to read as they can just pick which heading they prefer to read. I have noticed the “oncofertility timeline” is located at the very bottom, it would be a good idea to move it to the top to show the audience the progression and history of oncofertility.

It is great to see that you have make the use of bullet points; as a reader I would prefer to see a bullet dot rather than a hyphen (-). I know this may be a small thing to change but it will look a lot neater. The videos used in this page is very insightful and interesting, this will keep the audience intrigued. It is clear that some areas have not been focused on such as “Artificial Insemination”, “In-Vitro Fertilisation”, “Oncofertility timeline”, “Unique chemotherapy drugs” and “How does it effect the cancer cells”. With more research I am sure these areas can be successfully improved.

Extensive research have been conducted which is great to see however some references have not been cited correctly, as they are no present under the references (33, 45) while a few are repetitive (26/27, 24/25), 19 is just inconsistence. Just a reminder that references are requires in the body of the page; so just proof read everything and include the references.

Overall, the page is outstanding. The content and videos shows the amount of effort you guys have put into this Wikipage. With these peer assessments, I am certain that the page will improve a lot!

User:Z3463514

2015-10-15T12:03:21Z

Z3463514:

Talk:2015 Group Project 3

2015-10-15T12:02:50Z

Z3463514:

{{ANAT2341Project2015discussionheader}}

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:19, 25 September 2015 (AEST) OK so this is far from ready for peer assessment. This is a very large topic with many possible sub-headings (missing from your project page) as well as animal models and environmental/genetic information. I cannot see any illustrations, images, media, resources added to the project page to illustrate the topic and give a balance to the content.

--[[User:Z3416054|Z3416054]] ([[User talk:Z3416054|talk]]) 02:07, 27 September 2015 (AEST) Hey guys, where do you think we should include animal models? Also I think it'd be a pretty snazzy idea to have a cartoon/photograph of polycystic ovaries in the intro and then for causes/pathogenesis have a flow chart or something similar

----[[User:Z3416054|Z3416054]] ([[User talk:Z3416054|talk]]) 16:20, 27 September 2015 (AEST) Hey guys, I've found some pretty snazzy images of polycystic ovaries, but do you know if we have to find the copy right information to be able to use the images? Most of the images come from google-image linked sites and don't really give much information on usage

--[[User:Z3459224|Z3459224]] ([[User talk:Z3459224|talk]]) 14:40, 29 September 2015 (AEST) Yeah I'm pretty sure we have to find the copy right information for all our images. I think it would be best if we try to find images on Pubmed first. If not we can use other journal databases.

--[[User:Z3416054|Z3416054]] ([[User talk:Z3416054|talk]]) 16:51, 30 September 2015 (AEST) Agreed, I'll get rid of the one I put up as I couldn't really find any copyright information for it. I'll have another browse of pubmed and see what I can find

----[[User:Z3416054|Z3416054]] ([[User talk:Z3416054|talk]]) 17:35, 30 September 2015 (AEST) I uploaded a new image/flowchart with some proper referencing. I'm thinking that my discussion of pathogenesis will largely be on insulin resistance and hyperandrogenemia

--[[User:Z3459224|Z3459224]] ([[User talk:Z3459224|talk]]) 12:24, 2 October 2015 (AEST) That sounds good! If you need any articles, let me know. I came across a few articles on pathogenesis.

--[[User:Z3416054|Z3416054]] ([[User talk:Z3416054|talk]]) 14:03, 6 October 2015 (AEDT) Howdy guys! I added an image of some polycysts present on the polycystic ovaries of a rat. It's nothing too amazing, but if you think it's not necessary/appropriate for the section let me know and I can find another pic
'''Sub-headings'''
]

==Peer Asssessment==

===1===

I'm a little confused as to what your actual topic is? Is it female infertility or polycystic ovarian syndrome? I think it is important to clarify that so as the reader of your page continues reading, they know the exact topic they are reading about. I also think that where you have written “definition” under the big picture of the PCOS ovaries, it should say “epidemiology” as that is more what it sounds like. I also think the picture should be below the information, that way we know a bit better what we’re looking at.

I love the little purple box of information under the “Definition” as it stands out and is pleasing to the eye. The purple boxes throughout the page are really great! The image next to it is also really good as it is clear and relates back to the information beside it. Great use of images! They are all relevant and placed well and the hand drawn image is done well. Your “pathogenesis” section is great as are your sections “diagnosis” and “prevention and treatment”. Detailed and easy to read. It was great to see scientific and animal models throughout the page. Perhaps it would be good to include a little more information linking directly to the literature for more advanced readers. I would also suggest adding a glossary to the bottom of your page, as for people with little to no scientific background who may read this, they may not understand all the words and terms.

It appears under the subheading “environmental factors” that there is no referencing? However, aside from that you have an extensive references list and have referenced correctly and thoroughly throughout the page. I would also suggest adding a bit more information under the heading “causes” aside for the subheading “genetics” as the other sections look a bit bare. The layout is great, easy to read and follow however one suggestion may be to get rid of the underline below your subheadings. It just may make things look a little less clustered and final.

You seem to have covered all the key points pertaining to your topic, however, a section on complications of either PCOS or female infertility may be good to add. Your content and headings are good and references are cited properly. I would suggest perhaps relating it back a bit more to the basics of embryology and discuss what a pregnancy would be a life is a woman with PCOS did get pregnant. Overall, this is a really great page with a good layout that flows well. Keep up the good work!

===2===
This project page is nicely organized, and well balanced with graphs, tables, and diagrams. It is wise to narrow down the topic and focus on the female infertility caused by polycystic Ovarian Syndrome. But it will be better if the other possible causes are mentioned at the beginning.

The image ‘ PCOS Ovary vs. Non-PCOS Ovary’ explains the differences between normal and PCOS Ovary very well. It will be better if the image is inserted after the texts which define PCOS as it causes confusion about your topic at the current location.

The use of colour highlighting is very impressive. It do make the important messages stand out.

This Page has correct referencing. Current scientific researches are nicely summarized and fitted into the context. It is impressive to include animal and cell culture models in the pathogenesis section.

Overall, the wiki page has covered the topic well. Contents are concise and easy to understand. It would be better if a ‘glossary’ can be added to explain some of the terminologies for readers.

===3===

First and foremost the PCOS Ovary Vs Non-PCOS Ovary hand drawn image is amazing and its placement at the beginning really drew in my attention to the topic. I also particularly liked the purple theme set up throughout the wikipage, I thought it really helped bring the page together.The headings, subheadings and images are all set out neatly making it very presentable and easy to follow. The language used was also very engaging which is always a plus. Content wise there seems to be sufficient information under most of the headings which really showed your efforts and elaborate research on the topic. The only portion that wasn’t particularly well present was the environmental factors. I felt like it needs the inclusion of some examples.

To improve your page I would like to suggest the addition of a glossary that you could use to briefly define some terms such as ‘Hirsutism’ to allow a better understanding of the text. Additionally, I also noticed that under the ‘Hyperandrogenemia’ heading there was the use of the acronyms ‘GnRH’ and ‘LH’. Be sure to express the full term placing the acronym in brackets upon their first appearance before extensive use. I saw that this was done in the following paragraph where LH was initially correctly expressed as Luteinising Hormone but again this should be done at its very first appearance. The page also lacked some history surrounding the origin of the disease and how some of the treatments were established so that could also be included.

Overall, the presentation of the page gave me the impression of a good understanding of the topic so well done guys! Keep up the good work.

===4===

Really good introduction! It clearly outlines what is in the page and it serves to summarise the topic and highlight the areas that you will be addressing. It includes in-text citations and I’d like to acknowledge the hand drawn diagram and the efforts taken to do that. Great job. However, it is a bit pixelated so maybe try resizing the image to a smaller size.

This project was done really well. All key points, i.e. “causes”, “Pathogenesis”, “Signs and Symptoms” and etc., were clearly described. In terms of content, this group did a great job. It is very informative and all information they have included are relevant to the topic. There is a great deal of information that is presented in a strong manner with the use of adequate images, tables and diagrams. Images and diagrams can help summaries what some of the paragraphs communicate. For the” Prevention and Treatment”, your table is fantastic as it is informative, concise and relevant to the topic. Use of tables is always beneficial as it makes the page more inviting. Otherwise the page appears to overwhelming with just written content and no visual content to reinforce concepts and information. This was the case for previous groups so well done on that. There is an extensive list of references, which demonstrates, a great effort towards researching your projects system. Only for one of the references which is not from PubMed, you need to put into in the correct format and add the exact date you visited the website.

On the down side, there is an inconsistency in the amount of information throughout the page. Some sections lack information more than others for example you need more information for “Environmental Factors “and “Medications”. Thus, this can be a room for improvement to insure further research is done in those sections. I believe, this is a very large topic with many possible sub-headings so try to come up with more sub-heading. Yes, you mentioned animal models and environmental/genetic information but you need to do more research as these sections must be in more depth and more explanations. Most of the sections have great amount of detail with a number of in text citations and this is great to see. However I do notice that there is no videos what so ever, not sure if you are having trouble finding, or if you have left this until the last thing. Consider some youtube videos. This could help balance the amount of text you have, making the page more interesting. The project could also benefit from having a ‘Glossary’ list so that viewers can understand some uncommon words. A glossary list should be incorporated in a separate subheading. If you are having a plan to add more information to the page, splitting it into bullet points from now on might be a better way of organising it so peers get a more effective learning experience when they read it.

Overall, this is a good project page, well done group and best of wishes!!

===5===
Currently, this Wikipage is very impressive through the incorporation of numerous images, and tables. Because this page is mainly focused on PCOS I feel as though you should either remove “Female Infertility” from the title of the page or at least give an overview of other factors that may cause female infertility in the introduction.

The amount of images that have been used in this project page is highly commendable. The hand drawn image in particular, is very simple and clearly demonstrates the morphology of PCOS in comparison to a normal ovary. You have used a variety of diagrams to show various aspects of PCOS thus making the page very intriguing to the reader. Perhaps you could use videos or gifs to further explain diagnostic tools and pathogenesis of the disease.

I am also finding that there are inconsistencies throughout each section of the page. For example, under “Causes” there is a lot of information about genetic factors in comparison to the one line explaining that there are environmental aspects associated with PCOS. Perhaps you could look more into this aetiological factor and “Obesity and Diet” and refer to specific studies that prove this. Again for “Medication”, consider listing a few examples that are known to be an associated risk for PCOS. Also when discussing signs and symptoms of PCOS, you mentioned infertility. Since you stated in the introduction that PCOS is the most common cause of infertility, you should expand more on this mechanism and why it does this.

The layout of the tables and colour scheme is consistent, making it appealing to the reader. However for the “Current Treatments” table, consider adding another column to address the advantages of each. Success rates are provided but further explanation on their benefits would be great. Grouping prevention and current treatments together, it seems as though you forgot to add preventative measures in an obvious way. A few sentences on this should be enough to clearly state this. Also consider putting a glossary as you have used terms such as 'hirsutism', and mentioned hormones GH and LH without initially writing their full names.

Your group has shown extensive research and correct citations for each reference. As a reader of your page, I suggest that more of your research should focus on specific studies to support the content and on topics that are lacking important information such as “New Trials”, “Current Treatments” and “Causes”.

This page has a very good framework and structure. Adding more content, relevant pictures and references will ensure a great final page.

===6===

The progress you have made on your project so far is exceptional. Your key points are clearly taught at a peer level and your choice of headings, diagrams and tables so far has been well thought out. I especially commend you on a great drawing in the top of your page. It is drawn clearly and is a great depiction of the uterus and ovaries from the outside and inside and of Polycystic Ovarian Syndrome. Your introduction and epidemiology is beautifully complemented with the map you have included and the addition of a coloured box to highlight the definition of PCOS as the focus.

It is evident you have conducted wide and extensive significant research that also goes beyond the teaching aspect. This is clear through your inclusion of specific studies, explanation of animal models and cell culture models used in PCOS and the thorough description of your key points due to your extensive research. Well done on using all pubmed articles except for one!

Some suggestions on editing your work would be to briefly mention the cysts in your definition for PCOS since it is a main element of PCOS as depicted in your drawn image at the beginning of your page. The environmental factors are too vague, you could elaborate on this by including examples of environmental factors or explaining why the constant gene pool would indicate environmental factors in the aetiology of PCOS. You could also consider adding an advantages column to your treatment table if it is relevant. Also, while you have provided a great overview of PCOS, maybe also consider adding brief descriptions of other causes of infertility in women since it is your topic area with a focus on PCOS.

Some minor adjustments to make are to remember to add the retrieval date to the website you have used in reference 6. Also, you should increase the size of the map under the definition heading so that the percentages are readable and the country locations more visible and the flow chart under hyperinsulinemia so that it is clearer and the words are more readable by increasing the resolution of your files. The project is coming along great, your thorough effort into the project is evident.

===7===

As a first impression, this page is remarkable and provides a very thorough description, explanation and presentation of facts about PCOS. I really like the first image as it immediately caught my eye and demonstrated the differences between an affected ovary and a normal ovary in an easy to understand way. Furthermore the information under the "definition" section was very interesting, however I think maybe re-naming this would be more beneficial because at first I was a little confused about the topic, whether it was focusing more on female infertility or PCOS as a cause of infertility.

Other strengths of this page were the clear and well thought out lay out that allowed easy movement through the page and a logical progression of subheadings. Lastly, the "Pathogenesis" section is exceptionally researched and the range of resources you used highlights the extent and detail of your research- something that you all should be very proud of.

Some areas of improvement include providing more in depth information on some of the sub-headings in the "causes" section including environmental factors, obesity and diet and medication. More information on these areas would really aid in providing a thorough explanation and furthering the readers understanding of the topic. The inclusion of some more visual aids such as a video and maybe even some images or graphs/tabels in the "causes" section to break up the bulk of text. Finally, the inclusion of a glossary at the end of the page would be very useful- especially when considering this page is forwards-facing and can be accessed by the public; some sentences and paragraphs are very dense and use a lot of jargon and terminology that could be further defined in a glossary.

On a light note to end, the little touches such as the bold text throughout the paragraphs highlighting important words and key concepts, as well as the recurrence of the purple colour throughout the page really brought the wiki together and contributed to the flow and overall aesthetic of the page. Overall, you guys have done an awesome job!! Good luck with your final edits!!

===8===
Wow! The photo very encapsulate the audience and the topic itself. It is great how you used a lot of visual aids for your page, especially the hand drawn images which is very simple to understand the morphology differences of PCOS a normal ovary. All these visual aids attracts the audiences’ attention. After reading through the majority of the sections, I realised that some content are inconsistent with each other. It is a good idea to proof read all the sections and make sure that all information are integrated cohesively. As for the table under “Current Treatment”, since you have a column for disadvantages, it would be a good idea to add another column comparing it to the advantages.

I have also realised that you guys have not added a glossary; it is very beneficial for the audience as some might not have been introduced to scientific names. Make sure you write their full names then have the abbreviations in brackets to introduce a new term. [Luteinising Hormone (LH)]

There were a few grammatical and spelling errors; for example under “Blood Test” you have mentioned ‘Thyroid Stimulating Hormone’ however you have named it LSH. Shouldn’t it be “TSH”? It is important to proof read and ensure that the information is consistent. It would be great to see more images supporting “Gynecologic ultrasonography” and “magnetic resonance imaging”. The amount of resources found shows that extensive literature research have been conducted. All the references were also cited correctly.

This page has an excellent structure, by adding more detailed diagrams, content and references will improve the page even more!

User:Z3463514

2015-10-15T11:16:16Z

Z3463514:

Talk:2015 Group Project 2

2015-10-15T11:15:36Z

Z3463514:

{{ANAT2341Project2015discussionheader}}

--[[User:Z5016784|Z5016784]] ([[User talk:Z5016784|talk]]) 14:42, 13 October 2015 (AEDT) Just regarding the peer reviewing of other group projects, do we have to be assessing all 5 other projects?

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:16, 25 September 2015 (AEST) Hmm still a little thin. There should be some animal model info, histology images, physiological data, drug info, and genetic information.

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 17:15, 18 August 2015 (AEST) Hello there

--[[User:Z3415911|Z3415911]] ([[User talk:Z3415911|talk]]) 16:12, 24 August 2015 (AEST) Hey guys! So I've gone and added a few subheadings that may be useful to start researching. For this weeks assessment we need to choose one each and find 3 articles to go with it etc. So if we all choose one and start researching it, that would be good :)

--[[User:Z3415911|Z3415911]] ([[User talk:Z3415911|talk]]) 11:02, 26 August 2015 (AEST) Good article for treatment http://humupd.oxfordjournals.org/content/16/5/459.abstract?etoc

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 19:20, 26 August 2015 (AEST) Sweet, Thanks for putting up those headings to get things going. Lets all put up related documents by Thursday so we have can discuss things at the Lab this Friday!

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 19:29, 26 August 2015 (AEST) I've put up some interesting pubmed documents on our main page, Have a read through them (I haven't read them all yet)

=== '''Classifications of Ovarian Hyper-stimulation Syndrome''' ===
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Classification'''
! scope="col" width="650px"| '''Symptoms'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Mild'''
|style="height: 75px; background: #CCEEEE;"| '''Grade 1''' - Abdominal distention and discomfort
'''Grade 2''' - Abdominal distention, discomfort with nausea, vomiting and/or diarrhea and ovarian enlargement from 5~12cm
|-
|style="text-align:center; background: #EEEEEE;"| '''Moderate'''
|style="height: 75px; background: #EEEEEE;"| '''Grade 3''' - All features of Mild OHSS with ultrasonographic evidence of ascites
|-
|style="text-align:center; background: #CCEEEE;"| '''Severe'''
|style="height: 75px; background: #CCEEEE;"| '''Grade 4''' - All features of Moderate OHSS with the addition of clinical evidence of ascites and breathing difficulties present
'''Grade 5''' - All of the above symptoms along with a change in the blood volume, increased blood viscosity due to coagulation and diminished renal function
|}

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 11:40, 28 August 2015 (AEST) I wont be able to make it to uni today for the lab and the meetup after it. Got to take my cousin to the ER

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 12:07, 28 August 2015 (AEST) I was thinking to include the risk factors in the 'causative' subheading

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 13:22, 28 August 2015 (AEST) So basically in the Causative subheading, I was planning
1) Identify the different causes (including primary and secondary risk factors)
2) What difference occurs from a normal cycle (e.g. level of hCG normally)

--[[User:Z3415911|Z3415911]] ([[User talk:Z3415911|talk]]) 13:36, 28 August 2015 (AEST) No problem! I hope your cousin is okay. Whoever added a sub heading called: Tests and Diagnosis, there already is the same kind of subheading, Symptoms and Diagnosis so we need to merge the two. It also needs to be in chronological order

--[[User:Z3372824|Z3372824]] ([[User talk:Z3372824|talk]]) 13:46, 28 August 2015 (AEST)Hope he gets well! Talking about sections, I'll try and work on Prevention, and get the research summaries done for that section by next week.

--[[User:Z3372824|Z3372824]] ([[User talk:Z3372824|talk]]) 14:00, 28 August 2015 (AEST) J and I had a little discussion about how we're going to go about completing this. We can all work on each others sections and collaborate that way. Let's focus on finding research articles, collating them, referencing them i.e. get to the meat of the matter. Once we've done that we can cut to the point and make it more easy-to-read/user-friendly. We also think that our 1 wiki page reference should be the OHSS Wiki page. Also, when writing about your section, always compare/refer to the Controlled Ovarian Stimulation case. Bring those picture/youtube suggestions in!

--[[User:Z3374116|Z3374116]] ([[User talk:Z3374116|talk]]) 00:12, 29 August 2015 (AEST) Sweet, thanks for the info. Will be on the lookout for youtube clips and pictures. Is the OHSS wikipage you are referring to https://en.wikipedia.org/wiki/Ovarian_hyperstimulation_syndrome
this one?? And I agree on helping each other with respective sections and then cutting it down to the fine details

--[[User:Z3415911|Z3415911]] ([[User talk:Z3415911|talk]]) 21:49, 1 September 2015 (AEST) Yes, that's the wiki page :) I have already started taking down information from it in each section so when you see '''[OHSS Wiki]''', that's where the information is from. I just don't know how to reference something that is not pubmed yet haha

--[[User:Z3415911|Z3415911]] ([[User talk:Z3415911|talk]]) 22:11, 1 September 2015 (AEST) Also guys please note, I have not used any info. from wiki in regards to TREATMENT and PREVENTION as it appears someone is already working on those subheadings and I don't want to interfere, so yea, that info. is still out there for you guys to use.

--[[User:Z3415911|Z3415911]] ([[User talk:Z3415911|talk]]) 11:51, 13 September 2015 (AEST) Hey guys, can everyone please send me an email with your full names so I can add you on fb and make group. I feel like we need a better way of communicating. Thanks, z3415911@student.unsw.edu.au.

--[[User:Z5016784|Z5016784]] ([[User talk:Z5016784|talk]]) 16:25, 13 October 2015 (AEDT) Hey guys, i am working on a few sections, mark said not to add to the project until the peer assessments are done, so i was thinking of bringing my information to class on Friday so yous can have a look and see if it is useful enough, i will place the link to one article, it has two tables in there that i think can be used, what are your thoughts about them?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842872/

Video that J found!
http://www.howcast.com/videos/511910-ovarian-hyperstimulation-syndrome-infertility/

==Peer Review==

This wikipage is very well put together. Your choice of headings, subheadings and tables and images is remarkable, it definitely makes the whole page flow very well. I particularly like the hand-drawn image which does a great job at simplifying the process of the pathogenesis of OHSS.

The introduction very concisely explains the contents of the page and I liked how it was finished off with a statement about the aim of the page. I thought it really brought the introduction together nicely. I can’t say much about the content except that it is very engaging and very well written so well done guys! Keep up the good work!

Some suggestions I have that could improve your page include adding more images. It would be nice to have some graphs to complement the statistical date from the epidemiology. Also, in some of the paragraphs e.g. in the last paragraph of ‘Epidemiology’ there isn’t a citation that accounts for the information at the end of the paragraph so that should be fixed.

----

This page clearly and efficiently explains the topic of choice. It covers all relevant matters well and the text is descriptive and informative. After reading the page, I felt as though I had a greater understanding of the topic. The subheadings used are good, and are placed appropriately in order - providing an element of cohesiveness between the page and the topic in general. Good use of linking statements – connecting all the elements discussed on the page.

There is however an excessive amount of text used. Although the information is relevant and informative, the page is dense and reading all at once is tiresome. Reducing/sifting through the amount of text on the page – and also adding a great deal more media files will help to break up the denseness of the page. There is only 1 image on the whole page – greater attention needs to be paid to alternative media files and sources to help break up the page. Additional media files will also add to increasing the understanding of readers.
The diagram drawn is neat and cited correctly. --[[User:Z5015534|Z5015534]] ([[User talk:Z5015534|talk]]) 15:07, 13 October 2015 (AEDT)

----
This Wiki covers the topic well. The content is very well written and easy to understand. Images and texts are correctly cited and referenced. In some of the sections, eg, ‘Ovulation Induction’, ‘Avoiding hCG during Luteal Phase Support’, more in-text reference will need to be added.

It is a great idea to have some bold texts in lines, which highlight the main points of paragraphs, and help readers to understand when skimming.

The hand-draw diagram of ‘pathogenesis of OHSS’ is excellent. It is well structured, and easy to understand and memorize. It will be great if more images, diagrams, videos can be added to the other sections.

Overall, the project page is very well developed. Some of the sections need to have more work on though. It would be nice if more graphs and tables can be added to balance the texts.

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So far your wiki page gives a very good coverage of Ovarian Hyper-Stimulation Syndrome. The progression of your subheadings progresses logically from one topic to another. It's good to see that you've included an excellent hand-drawn image which is well suited to the 'pathophysiology' subheading. The amount of textual information you have under each heading is vast and gives a comprehensive description of OHSS. Furthermore, you have an excellent range of sources to support your discussion.

I feel however that asides from your hand-drawn image, your use of images and other source of media is definitely lacking. As is, your page is largely text with little to no breaks, making it quite difficult to read. The use of images would not only help break up the monotony of the text, but also help reinforce some of your ideas. I feel that the inclusion of images in the 'symptoms' and 'complications' subheadings would be suitable.

It may also be worthwhile to include subheadings concerning current research, to inform readers about contemporary developments regarding OHSS. Furthermore, 'future research' could also be another potential subheading and could illuminate potential areas that are beginning to be or could be investigated in coming years.

Overall, a very impressive page so far, that could be enhanced with the addition of relevant images and other media.

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Great work, it looks like your group has a clear mindset and direction to where your group project is going, even if it is not there yet. Also great introduction! Your entire page's contents were introduced well and simple. However, all Text and no images were included except one image. Not a good look to go through. The information here is good but is also very dense and hard to follow without any images. It would be great if you could break it up a bit with more images, tables, diagrams and hand drawn pictures. This style of writing is very professional and would be perfect for a report or essay; however as a wiki page it is too hard to follow. Breaking up the information into tables and short videos would allow you to guide the reader through your topic. Well done on the use of bullet points make it easy to follow. Only one hand drawn image as well as one table uploaded onto the page contains adequate information explaining them, which is good.

Well done on use of “Glossary” section. It is indeed necessary and important.

There has clearly been a lot of research and work put into this project and that is very commendable and I do appreciate it. However on a whole as I mentioned, there is too much information without having any interactive techniques such as tables, diagrams and etc. One of my suggestions is to make a table for “Prevention” or “Genetics” section or even both. I also suggest adding another subheading for “current research findings” or “Future research” which requires more time and research. Therefore you can include more journal articles in this section .In this section pictures would also be good to help understand and engage readers. Overall, well done on your written information for each section. They’re very relevant to the topic and to the project as well.

Some sections like “Effect on the Newborn” or “Animal Models” seem to be untouched. I’m assuming you are still in the process of adding content. Please be aware of the deadline. Moreover, in text citation is crucial which are missing in some paragraphs. Citations should be carried through the entire page to know exactly where you have got your information from. Good job on referencing at the end of the page. All research articles seem to be relevant to all sections.

Overall, it is a really good project with the potential to be excellent because of the amount of effort you have put into the research. Keep up the good work, but just edit and add those things I mentioned to the project and finish the sections you need to. Very well done so far and good luck with finishing the project off.

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I found your topic very intriguing! It appears as though you have put a lot of time into researching your area and ensuring that your have addressed the main concepts.

'''COMMENDATIONS'''

• Fantastic introduction! It gave me a clear overview of what your group’s topic is, and it was easy to understand.

• Great overview of the symptoms. Your table added some colour to the page and the information was succinct.

• You are to be commended on your hand drawn image - very clear and neat. Good job!

• Clear reference list and good in text citations.

'''RECOMMENDATIONS'''

• A map in the Epidemiology section would put your text into perspective for the reader.

• Some words have been typed in bold (particularly in the Diagnosis section). The selected words seem to be a bit random. Maybe you could highlight phrases rather than words, or organise the information under subheadings.

• More images would break up the information and aid the reader’s understanding of the given concepts. Subheadings would also help organise the information to place ease on reading and comprehension.

• Your page features large chunks of text for the most part. I would recommend reading through your text and removing excessive bits of information; try and be a bit more succinct. You could use more tables and diagrams to communicate certain concepts as well (e.g. Treatment and Diagnosis).

• Information is absent under “Animal Models” and “Effect on the Newborn.”

With this said, your group has covered all the key concepts and it is evident that you have done a lot of in depth research. You are definitely on the right track.

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Collectively, this page is well structured and shows you have a well-rounded understanding of this topic. The introduction encapsulates the whole topic extremely well and provides a good framework for the rest of the page. The headings are relevant and follow the structure to discuss a disease, thus being very easy for the reader to grasp the key concepts of the syndrome. Perhaps consider using bullet points in your “Causative Agents” section and “Prevention” heading. You can also utilize numerical steps to describe the pathogenesis of OHSS to accompany the well-structured diagram, and to break up the text in your page.

I have also noticed that the page is lacking subheadings in a few sections, thus it prevents the reader from knowing the key points that are being discussed and explained. Together with the subheadings that are already present, they can also be used under “Diagnosis” for each diagnostic tool, “Genetics” for VEGF, LHR and BMP-15, and possibly in the “Animal Models” section. The content under each of these headings however, is very interesting and has been written well, showing you have gained a thorough understanding of OHSS. I am certain the content you add for the untouched headings will also be of a high standard. On that note, further explanation about treatments and complications of OHSS could be added. These sections are currently lists therefore they can be further expanded with more research and videos to explain things like surgery procedures.

The glossary provided is extremely beneficial however; more diagrams, tables, and videos should be incorporated to further enhance the reader’s understanding. At the moment it is quite content heavy and needs visual aids to make the page more interesting and easy to read.

This page also demonstrates that you have thoroughly researched each aspect of OHSS, and have used recent studies to support the content added. The resources have all been cited correctly, but perhaps search for more literature to further support your claims and theory regarding OHSS.

I am really impressed with your page so far. Using more references, visual aids, and adjusting the format of this page will guarantee a successful mark. Well done!

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I’d like to start by commending you on an exceptional choice of key points which you have chosen to research and elaborate on. They provide a good overview of the subject for your readers. They are clearly explained and taught at a peer level without dragging on with irrelevant points. Your introduction is well written, I especially like that you have included the aim of you wikipage in the introduction and the key points you will be focusing on to orient your reader. Including epidemiology was also a good choice as it shows the relevance and impact of Ovarian-stimulation syndrome in society. I also find that including prevention and treatment is great for visitors without an embryology background who are looking for general information on the topic, especially for women who can learn to better reduce their risk since this page is accessible to the public.

Other great aspects of your page include the inclusion of a glossary for readers to refer to when they are unclear on the terminology and that you have used relevant sources. The table used to organize the symptoms makes its easy to read and understand. I particularly liked your section on the pathophysiology. Not only is it explained well but you have included a great hand drawn diagram that is clearly drawn, complements the adjacent paragraphs well and includes a statement with permission to other visitors to reuse it.

Going forward your main focus’ should be conducting further research to complete your remaining key points on the effects on the Newborn and animal models (very relevant for embryology peers). Also, focus on including more supporting diagrams and figures since so far you only have one. A histological image of the ovaries would be very appropriate to your topic. Make sure you read over your page to edit your grammar and wording for example in the phrase “they are given to assistive medication”. Your citing is well done, but make sure when you are referencing websites that you include the retrieval date such as in reference 11.

Overall your page is well written, with my main concern being is it sounds more like a report than a peer teaching page. You can fix this by adding more images, diagrams, figures and tables to break up the text and help to explain your content. Adding a video would also be engaging. Otherwise, great progress so far!

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Everyone seems to have already commented on your introduction, but it will not deter me from giving you another amazing high five! That introduction is so well thought out and structured that it has set up the entire page in an easy to read and easy to understand way- amazing work!! The page as a whole was fantastically structured and I found it very easy to follow which made the experience of reading and learning about the topic. Furthermore the topic was outstandingly researched with a wide variety of sources and really demonstrated the time and effort that you guys have put into it so great job; however, one thing that lets you down here is that there are some citations missing or large chunks of writing that are not cited which is a shame because it is evident that you have put in the time and effort. The language that has been used through out the page, although very formal, was appropriate and made it easy to understand the information. This was further aided by the inclusion of the glossary which is a necessity and was very well planned. I also really enjoyed the inclusion of the section "Epidemiology" as it provided a comprehensive snap shot and scope of the disease.

Some aspects that you could improve on include the inclusion of more images, videos, graphs and tables. Again, everyone seems to have commented on this, there is too much writing and it makes it difficult to follow and stay concentrated on the information. Another point to improve on would be further explanations about the treatment and prevention, this would be highly beneficial as it not only would provide information to students but also relevant and useful information to the public as the site is public facing. Lastly, the information missing below the “Effect on the Newborn” and “Animal Models” section will add another layer of detail and ultimately complete the page.

Overall, you guys have done an amazing job- the main area of improvement is the inclusion of more interactive and visual elements that can break up the chunks of texts and make the page more well-rounded. Awesome work and I look forward to seeing the end result!!

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This Wikipage is very well structured, the headings and subheadings are all very appropriate; the introduction presents the entire topic very well. This really grabs the attention of the audience as the structure of the page is very easy to navigate. “Epidemiology” was very easy to understand as you introduced all the jargon with its shortened name; good idea to add the glossary at the bottom defining all the scientific terms. It is very beneficial for those audience who have not been introduced to these scientific terms. “Causative Agents” was explained perfectly, which makes it easier for the audience to read. I also suggest using some bullet points and tables. It’s great to see the use of tables in “Symptoms”, it simplifies the content and makes it easier to categorise the different severity of the symptoms. As for “Diagnosis”, I suggest adding some subheading to separate the different ways of diagnosis (History, physical examination, ultrasound, further investigations etc). Make sure you add more subheading throughout the page, it highlights the key points for each heading for the audience. “Complications”, “Treatment” and “Prevention” has good use to subheadings, it is well structured and interesting to read. This shows that you have conducted adequate literature searches and have a deep understanding of OHSS. I suggest to add more information into complication, case studies or examples could be used.

I am impressed to see that you guys have drawn your own detailed diagram. However, I suggest that you add more diagrams, videos and tables; this can enhance the audience’s understanding towards OHSS. There is a lot content at this point which is great to see all the research you guys have conducted however, it need visual aids to make the page easier and more interesting to read. All the resources have been cited correctly but I think more research to support the page and enhance the validity of your information.

Overall, I am very happy with this page. Remember, more visual aids (diagrams, videos, tables and flowcharts). Great work!

User:Z3463514

2015-10-15T09:06:08Z

Z3463514:

User:Z3463514

2015-10-15T09:05:49Z

Z3463514:

Talk:2015 Group Project 1

2015-10-15T09:05:20Z

Z3463514:

{{ANAT2341Project2015discussionheader}}

==Stem cell presentation==
Hi, I have listed some papers which I am interested in doing because it is highly relevant to my own project. But I am more than happy if you post other papers and topics which interest you and we can work on them together and get ready earlier.

PMID 26295456

PMID 26439174

PMID 24837661

PMID 26418893

'''PMID 24981862'''

Hey, my pick would be C. Sturgeon et al. Wnt Signaling. purely on ease of doing a review. PMID 24837661. If that suites people. --[[User:Z3292373|Z3292373]] ([[User talk:Z3292373|talk]]) 15:51, 12 October 2015 (AEDT)
==Useful resources==

Here is a good source for overview and status of 3 Person IVF. http://www.geneticsandsociety.org/article.php?id=6527

==Mitochondria==
*discovered in muscle by Kölliker in 1857
*mitochondria are the "powerhouses" of the cell and the location where respiration occurs at the cellular level.
*mitochondria contain their own DNA (mitochondrial DNA or mtDNA) that has been originally inherited only from the oocyte (maternal inheritance).
*The spermatozoa (paternal) mitochondria- energy for fertilization motility but are generally destroyed during the first mitotic cell divisions.
*This pattern of inheritance has important implications for a variety of mitochondrial associated diseases, usually occurring in tissues requiring lots of energy (muscle, brain).

[[File:Mitochondria EM01.jpg|200px|thumb|Electron micrograph of mitochondria.]]

===Eukaryotic mitochondrial genomes===
*double stranded circular DNA (mitoDNA. mtDNA)
*1981 complete human sequence (16,569 nucleotides)
**37 genes
**encodes 13 polypeptides involved in oxidative phosphorylation
*remaining genes transfer RNA (tRNA) and ribosomal RNA (rRNA)
*multiple copies within the matrix
*maternally inherited
*remainder encoded by nuclear DNA
*proteins made in cytosol and imported into mitochondria

link to Embryology website [[Mitochondria]]

==Chat==

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:13, 25 September 2015 (AEST) OK so just text on your page to date and not yet a thorough coverage of the topic. Animal models, timeline, images, diseases.

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:07, 21 August 2015 (AEST) I think you will have 3 students and therefore will exist as a group.

--[[User:Z3251292|Z3251292]] ([[User talk:Z3251292|talk]]) 17:29, 21 August 2015 (AEST) hi all,sorry that I still could not make my way to uni today due to illness. I will definitely be back next week. I have added few sub-headings to the points you guys setup, feel free to change them. BTW, would you like to pick one of the 5 topics for now? and start working on it? or there was some good arrangement already? please let me know.

--[[User:Z3292373|Z3292373]] ([[User talk:Z3292373|talk]]) 20:51, 24 August 2015 (AEST) Hey, ummm sorry i lead us astray putting up those headings ''female fertility'' had been taken so we have to pick another. I put up the list of ones left. My choice would be three parent ivf. So ill do a bit of research and on that now (add some headings)just 'cuase i got some free time, but by all means if you guys would like to do something else that interests you I'm more then happy to change.

--[[User:Z3251292|Z3251292]] ([[User talk:Z3251292|talk]]) 13:19, 27 August 2015 (AEST) Hi all, I am good with your choice. let's work on 3 person embryo. i have added few papers I find good on this topic.

===General===

Note to self doing history benifits.

===Section===

==Peer Reviews==

===1===
This wiki page does well in covering a lot of areas relating to the topic, however the website does not outline the information found/used quite clear enough or to the right extent. The page would benefit largely in focusing much more attention to the mechanics of the process itself and how it physically works. There is lots of information regarding other various aspects relating to the topic, however the fundamentals of the topic are not clearly discussed on the page, and it is not clear what goes on in the process.

The page should also fix up some grammatical and syntax errors. Read through the page carefully and ensure all paragraphs make sense ensuring that the quality of the information portrayed is fully appreciated. To also make the page clearer, some thought should be given to rethinking the order of the subheadings. Having a natural cohesion throughout the page as a whole is important – some subheadings do not fit into place correctly and could be moved around a little bit. Also having linking sentences within paragraphs – involving each subheading with others and the topic as a whole – will make the page much more cohesive.

The page used a good amount of supporting pubmed articles, hwoever more images/media files could be used to break up the concentrated use of text. The video used is relevant and informative – however there is no copyright information.--[[User:Z5015534|Z5015534]] ([[User talk:Z5015534|talk]]) 22:44, 10 October 2015 (AEDT)

===2===
Hi guys! I'll start of by saying that the images and video you have included are excellent and are relevant to your topic of discussion. Also, you have a large number of reliable references which is good to see. However you have yet to include a hand drawn image, which is required for the wiki page. I feel like you could probably eliminate the typed out 'timeline of mitochondrial donation' and instead use this as an opportunity to use a hand drawn image of the timeline. Furthermore, the timeline under 'cystoplasmic transfer' feels a bit awkward and unnecessary. You could probably include this timeline alongside the 'timeline of mitochondrial donation'.

Under the 'Technical Progression' section it would be best to incorporate human embryo, mouse and human models under a sub-sub heading, as at the moment it feels a bit jumbled.

I would also recommend moving the 'Benefits' heading towards the end of the page. It feels odd reading about the benefits of three person embryos before I gain a proper understanding of how they work. Also it might be worth talking about the disadvantages (if there are any) to three person embryos to balance out the 'benefits' section. As has been previously stated, make sure you sort out the copyright information for your video as it would be a shame to lose marks if it was missing. Also, don't forget to add the 'student template' to the 'Swapping mitochondrial DNA mammalian oocytes' image as it is currently absent.

===3===
The entire project is presented simplistically and all the content is relevant and easy to understand. Majority of the flaws I found were based around poor grammar and syntax which could be fixed up with some editing. Below is a more detailed breakdown of some of the things you could fix.

Firstly, I liked that the introduction was brief and concise and gives the reader a basic understanding of the topic of three person embryo. The video was also informative and provided some background information around the topic. I was informed that mitochondrial DNA was the major factor concerning this topic however there was a lack of information about its importance to the body so a short summary could be included along with some examples of diseases it could cause.

Also, the use of a timeline to present the history is a great idea and I think it could be improved and would look more aesthetically pleasing if it were to be placed into a table. I also think the 1990s, 2000s and 2010s label could be removed to make it look less clustered since they aren’t particularly necessary.

Some information under the heading ‘Technical Progression’ has yet to be filled in but from what is there I’d like to suggest exchanging the bullet points for numbering instead for the information under ‘Pronuclear transfer’ and ‘Polar body transfer’ since they sounded like sequence steps as opposed to separate points.

Finally, I found the layout of the table under the heading ‘Legal status’ to be very well put together. There are however some countries placed under the incorrect continents and I found that the order was easily changed and mixed up. I also noticed that several of the countries were linked to the same sources which made the information very unspecific. Instead of just links I think a few sentences explaining the legislation would be more informative.

===4===

I liked how you guys started the introduction and provides partially a brief overview of what your project is about. But I believe it is not enough to allow the audience an insight to your project page. This is something that needs to be worked on and maybe add some images also. However, the choice of short video used in the introduction is great. This is definitely a benefit for your page as it will reinforce the information you have been trying to get across. Like I mentioned, one thing you could work on is adding images and explaining the content in more depth. There is great amount of reference at the end of the page in the reference list which is fantastic!, however there is no in- text referencing in each section such as introduction or in some of the parts of the “Technical Progression” like “Cytoplasmic transfer” or “Spindle-chromosome transfer”. Having in-text referencing will allow the audience to know exactly where the information was read from and for the interest of the audience can read that specific paper in detail.

I also noticed that there are no information for “Benefits” and “Legal Status” or there is limited information for such headings like “Ethics”. I’m assuming you didn’t get the chance to upload information there or you haven’t had the time. This is something you need to work on so that the audience has some note of what this page is about. Also you need to change the format of the page for example it is to move the 'Benefits' heading towards the end of the page after the audience gained a good level of understanding of the project. You included some great images but be careful with copyright as I didn’t see it. But also consider some more images, tables, diagrams as well as hand drawn images in some sections, to make it more inviting and not overwhelming with just content. I do appreciate that the section of “Technical Progression” is subdivided into “Human Model”, timeline” and etc. But maybe consider adding in the current research, historic research, limitations and disadvantages to ensure that you can get all the marks possible by addressing all the key concepts. The timeline is a great idea that outlines the significant progresses and in turn helps put major events into perspective, making it more effective for students to study and understand.

Well done on making the “Glossary” at the end. This is exactly what I would have expected to see and I used it while I was reading through your page. Also it is great to see the table in the “Prohibited” section but I would suggest you to write some sentences explaining the legislation rather than just pasting the links.

Overall, this project page has room for improvement by giving certain sections of the page the attention they deserve. Images are imperative in allowing a balance between text and the image itself. Diagrams, tables and animations can sometimes be refreshing, and less overwhelming to see them among paragraphs of content. Try and work on time management, or set a group deadline that everyone has to meet so that all the information can be well up before the due date so your group can have time to edit and add images and play around with the page comfortably. Goodluck!

===5===

It would be nice if the history section could start earlier in time e.g. who came up with the idea of 3 person embryos. It kind of feels as though 3 person embryos popped out of nowhere. This is just a small nuance but the first sentence in “Hereditary mitochondrial Disease” doesn't really make sense. It sounds incomplete. I think you have too many timelines going on in your page and it makes it a bit confusing. There is one under “History” and another timeline in “technical progression”. I understand they may be timelines for different things, but it’s all too much history. Maybe the “technical progression” timeline could be simplified into a paragraph?

Some sections have too many subsections e.g. “technical progression”, and this makes the section messy and hard to read. It is however good for the table of contents though as it makes it easier to specify what you want to read on the page so my suggestion would be to keep some subheading but cut down a bit. You guys are listing papers to read too often. People want to have the information summarized for them on a wiki page, not have to outsource all the information themselves. It’s too time consuming and if they wanted to read a bunch of articles, they would go on PubMed themselves. However, I do like that some articles have been listed but maybe cut it down to one or two great ones instead of 4-5 etc.

I really like the table under the subheading “prohibited”, however, it would be nice to have a little summary next to the links about what each countries stance is, because again it’s too time consuming to have to read all those links. I also think some sections need a lot more work e.g. “ethics” and “benefits” and some more words could be added to the glossary. For example, a definition of what the word gamete mean would be good as, whilst we may know what it means, other people who view your page may not.

I really likes the images you used in “technical” progression. They were easy to understand and simplified the text a lot. It would be good however to add a few more images, perhaps to “history”. Some hand-drawn ones would be good. You've got a good amount of references in there, just maybe add a few more. This indicates that you have done significant research and they appear to be correctly cited. The key points of your topic are clearly described and I feel as though your intro., whilst short, really opens up the topic well. Your page relates well to the learning aims of embryology.

To conclude, I think you've got a great framework and some really good information in there. Just makes sure your page doesn't look too busy and is easy to read. A little bit more work needs to be done in some of the sections and a bit more technical touch ups and you should be good!

===6===

Your group’s topic looks very interesting! You have addressed the key points of your topic, and the placement of the video gives the reader a great overview of your project.

'''COMMENDATIONS:'''

• Information has been organised well most of the time. Good use of bullet points and subheadings.

• The table under “Prohibitions” is a great way of summarising information, and it was easy to read.

• I like the addition of a glossary, however, more terms could be added here as a lot of jargon has been used in your text.

• Cytoplasmic transfer images were great as they aided the text well. These images could be re-sized as some of the text is blurry.

'''RECOMMENDATIONS:'''

• Be mindful of spelling and capitalisation, e.g. “Hereditary Mitochondrial Disease” rather than “Hereditory mitochndrial Disease.”

• In terms of formatting, more spacing between major headings will make reading the page easier and will allow your information to flow.

• I recommend adopting a set formatting scheme for each section: i.e. make sure that the subheadings are all the same size, that they are in bold/italic (if that is what you intended).

• Some references and PMIDs are placed throughout the page. These should all be under your References heading at the end of the page.

• Information is missing under certain headings, e.g. “Mitochondria Linked Infertility.” I’m assuming that information from the two links provided will be summarised for the final submission.

• Hand drawn image is absent – maybe you could hand draw one of your timelines? (Seeing that both of them currently take the same format/structure).

Great job so far!

===7===

Thus far, I think this page has a good layout to be a successful page on Three Person Embryos. The headings and subheadings are relevant and show that you have conducted literature searches to deduce what information needs to be covered. I suggest moving “Benefits” below “Technical Progression” as it is important for the reader to understand the process of three person embryos, before learning its advantages. You could also add information about disadvantages and controversial issues.

On a positive note, I am impressed with the way you have set up headings under “Technical Progression”. The consistency of discussing a model and current research provides a systematic approach to the viewing of your page, making it easy to understand. Delving further in each of these subheadings would provide a greater understanding of the current technologies available, such as including limitations and advantages, and statistics of their success rates. The timeline under “Cytoplasmic Transfer” could probably be incorporated with the timeline under “History” to equalize the amount of content under each heading.

The content under each heading still needs work in terms of editing and elaboration. There are quite a lot of grammatical and spelling errors such as “Timeline of Mitocondrial Donation” (missing an ‘h’ in mitochondrial), and some sentences aren’t finished. Proofreading would be key to making the information more understandable and effective to the reader. Information seems to be lacking under a few headings especially “Benefits”, “Hereditary Mitochondrial Disease”, “Mitochondria linked Infertility” and “Other approaches”. To make it a bit easier for yourselves, you may want to consider using a table, flow chart for pathogenesis of the disease, and a detailed diagram of the relevant heading. You have provided a table to explain the "Prohibited Section" however a very short description/summary of each source in the table would be very helpful.

I also noticed you have not included many images, videos or tables. These visual aids really help the reader to understand the content in front of them, and also keep their interest in the topic so it imperative to focus on them as much as the content.

The references have all been cited correctly and have shown you have performed adequate research to cover the important information for this topic. As you add more information, more references should be present within the body of your page.

Overall, I think this page has a really good framework for further information to be added. With more editing, content and diagrams, you are sure to produce a wonderful Wiki page.

===8===
Your project instills a great first impression on a visitor to the page! It is a well designed webpage that doesn’t come across as overwhelming and too wordy encouraging and drawing the reader to explore your page. Your choice of content is relevant and provides a good understanding of the topic so far. The introduction is nice and succinct, explaining easily and clearly what the topic is about with a great video that complements the introduction. Together they give the reader good background information on the topic, and are taught in a way that’s easy for someone with no prior knowledge on the topic or in embryology in general to understand.

Furthermore, the timelines you provided, the ethics section and the table on the legal status of the technique is a good way of showing how far the concept has come and good at placing the technique in the context of how it has been translated into modern society. I really like that you have included animal models in explaining the various techniques, provided the current research available, and included further reading. This is very relevant and interesting for other embryology students and researchers who visit your page! The diagrams you have already chosen are very appropriate and explain the technique clearly to visual learners and are very engaging.

In improving on your page I think the main focus is to elaborate on some key points further and add a few more diagrams and pictures so you can maintain a perfect balance of words and images and the engaging layout you already have begun. For example, maybe for the section “hereditary mitochondrial disease” you can talk about the type of hereditary diseases there are. Also, some of your wording and grammar need further editing so make sure you go through and reread your work.

Other things you should edit include, adding a reference to your introductory paragraph and maybe clarifying that three person embryos are now legal in the UK since your video says “its on the threshold of acceptance”. Also check your copyright on some of the images such as the one that says “Copyright © 2015 BBC. The BBC is not responsible for the content of external sites. Read about our approach to external linking”, I am not sure if this means you are allowed to use it so just clarify this.

Overall, you have great progress on your page so far, it has a great teaching element to it and shows extensive research and citing into the project!

===9===
It’s great to begin with a introductory video which defines your topic. I do suggest finding a reference for the first paragraph for the introduction. Besides that, references have been cited correctly and shows that you have conducted extensive research, but remember to reference as you add information ( [##] ). I think you guys did a great job with the heading and subheadings; it shows us that you have done extensive literature research, and have came to a conclusion as to what information was relevant. Just a grammatical error made in “Timeline of Mitocondrial Donation” which is missing a H in mitochonidral. I suggest proof reading all the text before uploading! This will make it easier for the audience to understand and also for yourself! As to the “Benefit” heading, I think it will be a good idea to add information and case studies on disadvantages towards three person embryos.

Nice to see that you guys have included a timeline, this shows the progress made throughout the years. But I think there is still information that can be added into this area; for example: different possible approaches or more controversial issues that has emerged. “Technical Progression” is an impressive choice of heading; I found it very interesting to read. The cytoplasmic transfer images used were great! They were very easy to understand. The “Timeline” under “Cytoplasmic transfer” could be merged with the history timeline heading above.

Overall, I think more information and content needs to be added under all the headings and subheadings. To make it easier for the audience to read, I suggest adding detailed images, tables and flowcharts. It will be more eye-catching for readers and will keep them interested. I see that you guys have a table under “Prohibited Section” however that just leads to another link, rather than having the link there; I think it would be a great improvement if there is a short summary of all the sources found.

I think your page is organised and formatted very well! With more information/content, detailed diagrams and tables; it will further improve your Wiki Page! Good Luck.

2015 Group Project 4

2015-10-09T13:03:26Z

Z3463514: /* Diagnosis */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

==Background Information==
[[File:Components and structure of Spermatozoa.jpeg|300px|thumb|right|Virtual preparation of the spermatozoon showing the acrosome, the nucleus and nuclear envelopes, the mitochondrial sheath of the main piece of the flagellum]]
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|right|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=joTrmeDf1dY</html5media>

Infertility: Causes Behind Infertility <ref>St Pete Urology. (2011, September 14) Infertility: Causes Behind Infertility. Retrieved from https://www.youtube.com/watch?v=joTrmeDf1dY </ref>

===Major Causes of Male Infertility===

====Varicocele====

[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|right| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|right|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.<ref><pubmed>25685302</pubmed></ref>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|right|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocele Surgery====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval.

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==References==

<references/>

==External Resources==

2015 Group Project 4

2015-10-09T13:01:27Z

Z3463514: /* Testicular Colour Doppler Ultrasound */

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

==Background Information==
[[File:Components and structure of Spermatozoa.jpeg|300px|thumb|right|Virtual preparation of the spermatozoon showing the acrosome, the nucleus and nuclear envelopes, the mitochondrial sheath of the main piece of the flagellum]]
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|right|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=joTrmeDf1dY</html5media>

Infertility: Causes Behind Infertility <ref>St Pete Urology. (2011, September 14) Infertility: Causes Behind Infertility. Retrieved from https://www.youtube.com/watch?v=joTrmeDf1dY </ref>

===Major Causes of Male Infertility===

====Varicocele====

[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|right| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|right|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele. Colour Doppler Ultrasound can be used to measure the size of the pampiniform plexus and blood flow parameters of the spermatic vein. However, the reliability of the Colour Doppler Ultrasound to diagnose varicoceles remains controversial; the diagnostic criteria remain poorly defined, with considerable variation between investigators and researchers. Reflux is an important criterion for the diagnosis of varicocele. The change in color is subjective and unreliable for the diagnosis of reflux in the Colour Doppler Ultrasound examination and should be quantified with spectral Doppler analysis.

<ref><pubmed>25685302</pubmed></ref>

<pubmed>25038770</pubmed>

<pubmed>21243017</pubmed>

<pubmed>16903932</pubmed>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|right|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocele Surgery====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval.

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==References==

<references/>

==External Resources==

2015 Group Project 4

2015-10-09T12:58:09Z

Z3463514:

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

==Background Information==
[[File:Components and structure of Spermatozoa.jpeg|300px|thumb|right|Virtual preparation of the spermatozoon showing the acrosome, the nucleus and nuclear envelopes, the mitochondrial sheath of the main piece of the flagellum]]
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|right|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=joTrmeDf1dY</html5media>

Infertility: Causes Behind Infertility <ref>St Pete Urology. (2011, September 14) Infertility: Causes Behind Infertility. Retrieved from https://www.youtube.com/watch?v=joTrmeDf1dY </ref>

===Major Causes of Male Infertility===

====Varicocele====

[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|right| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Doppler Ultrasound===
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|right|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref> It allows the identification of minimal ectasia of the scrotal veins and minimal retrograde venous flow. Ultrasonography and particularly Colour DopplerUltrasound appear to be the most reliable and practical methods for diagnosing subclinical varicocele.<ref><pubmed>25685302</pubmed></ref>

<pubmed>25038770</pubmed>

<pubmed>21243017</pubmed>

<pubmed>16903932</pubmed>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|right|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocele Surgery====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

====Ejaculatory Duct Resection====
[[File:Midline Prostatic Cyst in Ejaculatory Duct Obstruction.jpeg|300px|thumb|right|Midline Prostatic Cyst in Ejaculatory Duct Obstruction]]

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a midline cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval.

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==References==

<references/>

==External Resources==

2015 Group Project 4

2015-10-09T12:50:06Z

Z3463514:

{{ANAT2341Project2015header}}

=Male Infertility=

Infertility is defined as the inability to achieve a clinical pregnancy after 12 months of unprotected sexual intercourse <ref>The World Health Organisation,. (2015). Human Reproductive Programme | Sexual and Reproductive Health. Retrieved 4 September 2015, from http://www.who.int/reproductivehealth/topics/infertility/definitions/en/ </ref>. Male infertility is the inability for a male to successfully impregnate a fertile female. Infertility is an ever increasing issue that affects one in six Australian couples as reported in the Australian Government Department of Health, ''National Women's Health Policy''. <ref>The Department of Health,. (2011). Department of Health | Fertility and infertility. Health.gov.au. Retrieved 2 September 2015, from http://www.health.gov.au/internet/publications/publishing.nsf/Content/womens-health-policy-toc~womens-health-policy-experiences~womens-health-policy-experiences-reproductive~womens-health-policy-experiences-reproductive-maternal~womens-health-policy-experiences-reproductive-maternal-fert</ref> Of these couples who are considered infertile, one in five experience problems that lie solely with the male.

==Background Information==
[[File:Components and structure of Spermatozoa.jpeg|300px|thumb|right|Virtual preparation of the spermatozoon showing the acrosome, the nucleus and nuclear envelopes, the mitochondrial sheath of the main piece of the flagellum]]
[[File:Structure of the seminiferous tubule.jpeg|300px|thumb|right|Structure of the seminiferous tubule: site of the germination, maturation, and transportation of the sperm cells within the male testes]]
===Structure of spermatozoa===
The shape of spermatozoa are suitable for the transport to female gametes via the uterine tube. For this reason the nucleus of the spermatozoa is highly condensed, covered by an acrosome filled with enzymes for establishing contact to the female gamete. The enzyme within the acrosome degrades the zona pellucida of the oocyte (female gamete), allowing membrane fusion. Spermatozoa also consist of a flagellum for progressive motility during the transport throughout the epididymal ducts. The motility is supported by the mitochondrial sheath found in the mid piece of the spermatozoa. <ref><pubmed>14617369</pubmed></ref> <ref>Holstein AF, Roosen-Runge EC. Atlas of Human Spermatogenesis. Berlin: Grosse; 1981</ref>

===Spermatogenesis===
The complete process of male germ cell development is called spermatogenesis, male germ cells develop in the seminiferous tubules of the testes throughout life from puberty to old age. The product of spermatogenesis are mature male gametes called spermatozoa. There are three major stages in spermatogenesis:

1. Spermatogoniogenesis

2. Maturation of spermatocytes

3. Spermiogenesis (which is the cytodifferentiation of spermatids)

Spermatogoniogenesis is the process where spermatogonia multiplicate continuously in successive mitosis. However, the daughter cells will still be interconnected by cytoplasmic bridges and is only dissolved in advanced stages of spermatid development. The stage of meiosis is manifested through changes in the structure of the nucleus after the last spermatogonial division. Cells undergoing meiosis are called spermatocytes. As the process of meiosis comprises two divisions, cells before the first division are called primary spermatocytes and before the second division secondary spermatocytes. During the prophase the duplication of DNA, the condensation of chromosomes, the pairing of homologuous chromosomes and crossing over take place. After division the germ cells become secondary spermatocytes. They do not undergo DNA-replication and divide quickly to the spermatids. This results in four haploid cells, namely the spermatids. These differentiate into mature spermatids, a process called spermiogenesis which ends when the cells are released from the germinal epithelium. At this point, the free cells are called spermatozoa. During spermiogenesis three processes takes place; condensation of the nucleus, formation of acrosome cap filled with enzymes and the development of flagellum structures and their attachment to the head/mid piece of the developing spermatozoa. <ref><pubmed>14617369</pubmed></ref>

===Physiology of fertility in Males===
Normal reproductive functioning in males is controlled by gonadotropin releasing hormone (GnRH), androgens and gonadatropins. The correct metabolism and functioning of all three types of hormones is essential to the normal and efficient production of spermatazoa, as well as over all reproductive health. GnRH is synthesised and released by the hypothalamus, which stimulates the anterior pituitary to release two gonadatropins: follicle stimulating hormone (FSH) responsible for spermatogenesis in the Sertoli cells and luteinizing hormone (LH) responsible for stimulating the release of androgens by the Leydig cells. Testosterone, the primary androgen, is released into the testes and aids FSH by further promoting spermatogenesis. Furthermore, testosterone is vital to the normal development of many accessory reproductive organs, including the accessory glands. A negative feedback loop of testosterone and inhibin (secreted by Sertoli cells) acts on the anterior pituitary, either decreasing or stimulating the release of FSH and LH. <ref>Stanfield, L. C. Pearson New International Edition ''Principles of Human Physiology Fifth Edition''</ref>

==Male infertility disorders==

'''Types of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Type'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Oligospermia'''
|style="height: 50px; background: #CCEEEE;"| Low spermatozoon count
|-
|style="text-align:center; background: #EEEEEE;"| '''Asthenospermia (asthenozoospermia)'''
|style="height: 50px; background: #EEEEEE;"| Reduced motility of spermatozoa within the semen
|-
|style="text-align:center; background: #CCEEEE;"| '''Teratozoospermia'''
|style="height: 50px; background: #CCEEEE;"| Abnormal spermatozoa morphology within the semen
|-
|style="text-align:center; background: #EEEEEE;"| '''Oligoasthenozoospermia'''
|style="height: 50px; background: #EEEEEE;"| Combination of reduced motility of spermatozoa (asthenospermia) and low spermatozoa count (oligospermia)
|-
|style="text-align:center; background: #CCEEEE;"| '''Obstructive Azoospermia'''
|style="height: 50px; background: #CCEEEE;"| Absence of spermatozoa within the semen due to a blockage in the genital tract obstructing the pathway for sperm to enter the penis from the testes
|-
|style="text-align:center; background: #EEEEEE;"| '''Non-obstructive Azoospermia'''
|style="height: 50px; background: #EEEEEE;"| Absence of spermatozoa within the semen due to sperm producing cells being damaged or destroyed
|}

==Causes of Infertility==
Due to the increasing rates of male infertility worldwide, researchers have been focusing on aetiological factors for its treatment and prevention. There are numerous causes of male infertility, however, the most common causes are those that relate to the correct development and adequate supply of spermatozoa to result in pregnancy, or inefficient transport of spermatozoa. The three key parameters for assessing male infertility are spermatozoa count, viability and motility<ref><pubmed>21243017</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=joTrmeDf1dY</html5media>

Infertility: Causes Behind Infertility <ref>St Pete Urology. (2011, September 14) Infertility: Causes Behind Infertility. Retrieved from https://www.youtube.com/watch?v=joTrmeDf1dY </ref>

===Major Causes of Male Infertility===

====Varicocele====

[[File:Varicocele induced cytoplasmic apoptosis.jpg|thumb|right| Varicocele induced cytoplasmic level apoptosis in animals: inadequate energy supply results in the cells ability to utilise lipids as a secondary energy source to be reduced, therefore reducing normal cellular functioning and division and ultimately leading to cytoplasmic level apoptosis.]]

Varicocele is one of the leading causes of infertility in males and affects one third of individuals classified as infertile. Varicocele is the abnormal dilation of the internal spermatic veins and creamasteric veins from the panpiniform plexus as a result of back flow of blood. This downward flow of blood into the panpiniform plexus is due to the absence or presence of incomplete valves within the veins. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> As previously mentioned, the three key markers of spermatozoa quality and of male infertility, spermatozoa viability, count and motility, are also heavily associated with varicocele. <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref> Other causes of varicocele include an increase in programmed cell death (apoptosis), increased scrotal temperature of approximately 2.5 degrees Celcius and reduced androgen secretion leading to testosterone deprivation. <ref>Marmar, L.J. (2001) Varicocele and Male Infertility Part II: The pathophysiology of varicoceles in the light of current molecular and genetic information. ''Human Reproduction Update, Vol. 7, No. 5 pp. 461-472'' retrieved 2nd September 2015, from http://humupd.oxfordjournals.org/content/7/5/461.long</ref> Testosterone is one of the hormones that play a major role in the correct physiological functioning of the male reproductive system. It is therefore evident that a deprivation of testosterone severely affects the rate of production of spermatozoa, their maturation as well as the male reproductive systems ability to effectively ejaculate semen (related to the development of accessory glands).

====Male Reproductive Cancers====

Male reproductive cancers, including prostate cancer and testicular cancer, have been shown to dramatically decrease the quality of semen prior to treatment, being comparable with that of infertile and subfertile men. <ref><pubmed>25837470</pubmed></ref> A link between testicular cancer and male infertility has been established by the identification of Testicular Dysgenesis Syndrome (TDS). The improper or abnormal development of the testicles associated with TDS has direct links to Sertoli and Leydig cell disfunction leading to failure of gonocyte maturation and therefore insufficient or low production of mature spermatozoa; one of the key indicators of male infertility. <ref><pubmed>21044369</pubmed></ref>. Furthermore, the presence of tumors in the male reproductive system have systemic effects including immunological and cytotoxic effects on the germinal epithelial leading to reduction in the quality of sperm produced and changes in the processes of spermatogenesis. <ref><pubmed>15192446</pubmed></ref> Finally, it has also been suggested that the fever and malnutrition associated with cancer may lead to alterations in spermatogenesis, a large decrease in spermatozoa concentration and evem azoospermia, the absence of motile spermatozoa. <ref><pubmed>11929007</pubmed></ref>

====Chromosomal Abnormalities====

Chromosomal Abnormalities are responsible for approximately 5% of all cases of male factor infertility and result in azoospermia (absence of spermatozoa) and oligozoospermia (low spermatozoa concentration). <ref><pubmed>20103481</pubmed></ref> Aneuploidy is the presence of an incorrect number of chromosomes and is the most common error of chromosomal abnormality resulting in infertility. <ref><pubmed>16491264</pubmed></ref> Klinefelter syndrome occurs in approximately 5% of severe oligozoospermic and 10% of azoospermic men and causes the cessation of spermatogenesis at the primary spermatocyte stage. <ref><pubmed>15509635</pubmed></ref> Another aneuploidy associated with male infertility is Y-chromosome microdeletions, present in 10-15% of azoospermic and 5-10% of severe oligozoospermic men, that can result in lack of spermatozoa in ejaculate (AZFa deletion), arrest of spermatogenesis at primary spermatocyte stage (AZFb deletion) and low concentration of spermatozoa (AZFc deletion). <ref><pubmed>11294825</pubmed></ref><ref><pubmed>26385215</pubmed></ref>

====Damage to DNA====

[[File:Causes of Increased DNA Damage.jpg|thumb|right| Factors associated with an increase in the risk of DNA fragmentation resultant in male infertility.]]

DNA damage in the germ cell population of males has been shown to be a contributing factor to many adverse clinical outcomes including poor semen quality, low fertilisation rates and impaired pre-implantation development; an outcome significant in the use of Assisted Reproductive Technologies when treating infertility. <ref><pubmed>16793992</pubmed></ref> The integrity of spermatzoa can be negatively impacted by deficits in the DNA repair pathways resulting in decrease in germ cell survival and the production of spermatozoa. <ref><pubmed>18175790</pubmed></ref> It has been demonstrated that common inherited variants within genes that encode enzymes utilised in the mismatch repair pathway have a negative relationship with the maintenance of genome integrity, meiotic recombination and even gametogenesis, therefore increasing the risk of DNA damage in spermatozoa and male infertility. <ref><pubmed>22594646</pubmed></ref> Finally, it has been demonstrated that an increase in age is associated with increased spermatozoa DNA damage resulting in a decline in semen volume, spermatozoa motility and morphology and over all semen quality. <ref><pubmed>22429861</pubmed></ref>

====Lifestyle Factors====

[[File:Non-viable spermatazoa.jpg|thumb|right|Non-viable spermatozoa: Spermatozoa stained pink by eosin due to a damaged membrane resulting in poor semen quality.]]

There are numerous lifestyle factors that are associated with a decrease in male fertility that often cause irreversible damage to processes in gametogenesis resulting in poor semen quality. Tobacco smoking has been seen to increase risk of male infertility by up to 30% due to the competitive binding of cadmium to DNA polymerase, replacing zinc and causing damage to the testes. <ref name= PMID16192719><pubmed>16192719</pubmed></ref> It was also suggested by the same study that excessive alcohol intake has an adverse affect on spermatozoa quality and chromosome number. <ref name=PMID16192719><pubmed>16192719</pubmed></ref> Another lifestyle factor that produces adverse clinical outcomes to male infertility is obesity and its association with hypogonadatropic hypogonadism; a condition characterised by a decrease in functional activity of the gonads (hormone production and therefore gametogenesis). <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies conducted on animals demonstrates that a sensitivity to leptin in the hypothalamus as a result of obesity, decreases Kiss1 expression, therefore decreasing the release of gonadatropin releasing hormone (GnRH) and ultimately resulting in hypogonadatropic hypogonadism. <ref name=PMID21546379><pubmed>21546379</pubmed></ref> Studies have demonstrated vigorous physical exercise such as bicycle riding and horse riding, has been associated with urogenital disorders including erectile dysfunction, torsion of the spermatic cord and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>

====Immunological Infertility====

Spermatogenesis commences at puberty after the body has developed a neonatal immune tolerance, therefore, without the necessary and correctly functioning physiological mechanisms such as the blood-testis barrier to separate the spermatozoa from the body's immune response, Sperm-reactive antibodies (SpAb) form and can be found attached to spermatozoa or within the semen. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> SpAb's have been found present in approximately 5-6% of infertile males.<ref name=PMID12385832><pubmed>12385832</pubmed></ref> <ref name=PIMD2069684><pubmed>2069684</pubmed></ref> Various microbial pathogens can infect the testes via the circulating blood or the urogenital tract, which can result in orchitis (the inflammation of one or both testicles); characterised by the infiltration of leukocytes into the testes and damage of the seminiferous epithelium, ultimately contributing to male infertility. <ref><pubmed>24954222</pubmed></ref> The disruption of tight junctions within the epididymis, rete testes and even efferent ducts due to inflammation or trauma can result in the exposure of spermatozoa proteins to the immune system and therefore the formation of SpAb's. <ref name=PMID12385832><pubmed>12385832</pubmed></ref> The presence of SpAb's on the surface of spermatozoa contribute to infertility by causing agglutination in seminal plasma, reduced motility characterised by "shaking" of spermatozoa and even the reduced ability of spermatozoa to penetrate the cervical mucous of the female. <ref name=PMID12385832><pubmed>12385832</pubmed></ref>

==Diagnosis==
Male infertility is a widespread condition. There are different diagnostic techniques to detect male infertility, from medical histories, physical examinations to sophisticated tests such as blood tests, ultrasounds and semen analysis. Most cases, there are no obvious signs showing infertility. Sexual intercourse, erections and ejaculations occur usually without any difficulty; the quantity and sperm count of the ejaculated semen are not noticeable with the naked eye.

[[File:Stages of spermatogonia.jpeg|300px|thumb|right|Infertile patient with arrest of spermatogenesis at the stage of spermatogonia]]

===Physical examination===
The physical examination focuses on the size and consistency of the genitals (testicles, epididymus and vas deferens) but also the overall body build. Noting the distribution of body hair and presence or absence of gynecomastia, which is the enlargement of male breasts due to the imbalance of hormones or hormone therapy. In some cases, by examining the size and consistency of the scrotum it is possible to palpate whether or not the epididymis may have hardened from a possible inflammation. Other cases may suggest obstruction within the ducts,this is determined by observing and examining the prostate size and consistency, checking for the presence of cysts or enlarged seminal vesicles.<ref><pubmed>21243017</pubmed></ref> Varicoceles are the most common abnormal finding in infertile men, typically diagnosed by physical examination of Valsalca manoeuvre. It is performed by forceful attempts of exhalation against closed airways by closing one's mouth and pinching their nose while pressing out. This strain increases their intrathoracic pressure and causes the venous return to the heart to decrease and increases the peripheral venous pressure.<ref><pubmed>16903932</pubmed></ref>

Varicoceles can be diagnosed by conducting Valsalva manoeuvre. <ref><pubmed>16903932</pubmed></ref> <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>

'''Classifications of Valsalva manoeuvre'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Grade'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 1'''
|style="height: 50px; background: #CCEEEE;"| Varicocele (vein dilatation) only palpable during Valsalva manoeuvre on physical exam
* No dilationed instrascrotal veins
* Reflux in spermatic veins of the inguinal region during Valsalva manoeuvre
|-
|style="text-align:center; background: #EEEEEE;"| '''Grade 2'''
|style="height: 50px; background: #EEEEEE;"| Varicocele palpable on physical exam without Valsalva manoeuvre
* No major dilation in supine position
* Dilated veins up to lower pole of testis seen only in standing position
* Reflux at lower pole veins during Valsalva manoeuvre
|-
|style="text-align:center; background: #CCEEEE;"| '''Grade 3'''
|style="height: 50px; background: #CCEEEE;"| Varicocele visible through the scrotal skin without performing Valsalva manoeuvre
* Dilated veins
* Reflex without Valsalva manoeuvre
|}

===Semen Analysis===
Although the semen parameters of fertile men can vary, semen analysis is an initial and crucial laboratory test when determining male infertility. <ref><pubmed>21243017</pubmed></ref> Every 2 to 4 weeks, at least two semen samples should be collected. 2 to 4 days prior to the collection is the abstinence period; this is important as it will increase the sperm destiny by 25%. Semen samples are obtained by masturbation or by using a latex free, spermicide free condom during intercourse.

===Testicular Colour Dopple Ultrasound===
[[File:Color Doppler ultrasonography of varicocele.jpeg|300px|thumb|right|Color Doppler ultrasonography of varicocele. Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.]]
High resolution color Doppler ultrasound is a noninvasive means of simultaneously imaging and evaluating the blood flow to the testes in infertile men. An ultrasound machine that has a Doppler mode can see blood reverse direction in a varicocele with a Valsalva, increasing the sensitivity of the examination. <ref><pubmed>25685302</pubmed></ref> It is not generally performed as a routine examination, however physical examination may miss intrascrotal abnormalities readily detected by dopple ultrasound. Non-palpable intrascrotal abnormalities includes testicular and epididymal lesions and tumour. <ref><pubmed>16903932</pubmed></ref>

<pubmed>25038770</pubmed>

<pubmed>21243017</pubmed>

<pubmed>16903932</pubmed>

==Risk Factors and Prevention==

'''Risk Factors of Male Infertility'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Risk Factors'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Smoking'''
|style="height: 50px; background: #CCEEEE;"| Semen quality is significantly affected by cigarette smoke. Light smoking has been associated with asthenozoospermia and heavy smoking has been associated with asthenozoospermia, teratozoospermia and oligozoospermia. <ref><pubmed>17304390</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Alcohol Consumption'''
|style="height: 50px; background: #EEEEEE;"| Alcohol abuse in men has been associated with impaired production of testosterone and therefore infertility. <ref name= PMID20090219><pubmed> 20090219</pubmed></ref> One study demonstrated that a typical weekly alcohol consumption of ~40 units resulted in a 33% decrease is spermatozoa concentration. <ref><pubmed>25277121</pubmed></ref> Alcohol abuse adversely affects spermatozoa morphology and production ultimately causing asthenozoospermia and therefore reducing the quality of semen. <ref name= PMID20090219><pubmed>20090219</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Overweight/Obesity'''
|style="height: 50px; background: #CCEEEE;"| An increase in waist circumference is associated with impaired semen parameters in infertile men. <ref><pubmed>24306102</pubmed></ref> A high body mass index (BMI) is negatively associated with normal spermatozoa morphology, spermatozoa concentration and motility, total spermatozoa count and percentage of vital spermatozoa, therefore negatively affecting male fertility. <ref><pubmed>26067627</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Psychiatric Considerations'''
|style="height: 50px; background: #EEEEEE;"| Stress has been demonstrated to have a negative affect on fertility, reducing testosterone levels and spermatogenesis. <ref><pubmed>22177463</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Physical trauma'''
|style="height: 50px; background: #CCEEEE;"| It has been demonstrated that physical traumas and vigorous exercise (often a combination of the two) can result in adverse urogenital disorders such as torsion of the spermatic cord, penile thrombosis, hematuria and infertility. <ref name=PMID15716187><pubmed>15716187</pubmed></ref>
|}

==Treatments==

Current treatments for male infertility aim to eliminate the causative factors mentioned above. These may involve improving the male's fertility using drug therapies or surgical procedures, however many assisted reproductive technologies have been introduced and have proven successful. Both methods of treatment have shown evidence of efficacy, thus having great implications on infertile couples worldwide.

===Non-surgical Treatments===

In order to effectively treat male infertility, it is imperative to correctly identify the specific cause and contributing factors. Currently, the different treatment strategies used or investigated tend to the specific aetiological factors for male infertility. Apart from theoretically allowing natural conception, these treatments also have an implication on the assisted reproductive technologies (ARTs) that are currently available.
[[File:Development of Gonadotropin Preparations.jpeg|300px|thumb|right|Development of Gonadotropin Preparations]]

====Injectable Hormones & Fertility Drugs====

Hormonal imbalance is a non-obstructive cause for male infertility. The efficiency of spermatogenesis depends on stimulation and regulation mainly by gonadotropins, GnRH and testosterone, without which may cause infertility. Males that have a deficiency in these hormones are being targeted by research involving injectable hormones such as human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG), and Clomiphene citrate, a fertility drug. hCG and hMG are gonadotropins that are used to treat male hypogonadotropic hypogonadism (MHH), a condition associated with infertility causing an underproduction of sperm or testosterone, or both <ref name=PMID26019400><pubmed>26019400</pubmed></ref>. These gonadotropins have been utilised in infertile males to stimulate the synthesis of testosterone and sperm directly, bypassing the pituitary gland that normally releases gonadoptropins LH and FSH. LH triggers Leydig cells to release testosterone, and FSH plays a vital role in spermatogenesis maintenance as it promotes Sertoli cell maturation <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

Additionally, clomiphene citrate also increases secretion of GnRH from the hypothalamus, and FSH and LH from the pituitary gland by blocking feedback inhibition of serum estradiol <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Normally, males have more testosterone levels than estrogen however those with MHH and consequent infertility, may have the opposite <ref><pubmed>16422830</pubmed></ref>. This was investigated in a study conducted in 2013 by Hussein et al. showing that hCG, hMG and clomiphene citrate are suitable treatments particularly for azoospermia, increasing levels of FSH, LH and total testosterone <ref name=PMID22958644><pubmed>22958644</pubmed></ref>. Therefore the administration of these substances may correct abnormal hormone levels that contribute to male infertility, thus stimulates spermatogenesis to increase spermatozoa count, motility and viability.

====Antioxidants====

There has been increasing evidence that infertility may be directly linked to oxidative stress, thus various antioxidants have been experimented with to determine their efficacy as a treatment. Reactive oxygen species (ROS) formed during oxidation plays a vital role in sperm function, particularly in capacitation, acrosome reaction, hyperactivation and sperm-oocyte fusion <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. In low concentrations, ROS are essential for the synthesis of energy, and contribute to signal transduction pathways within the cell. Usually ROS levels are regulated by natural antioxidants within the seminal plasma <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. However an influx of ROS and/or a deficiency in antioxidants due to abnormal sperm or environmental stress, can lead to oxidative stress. Spermatozoal cell membranes contain high amounts of polyunsaturated fatty acids that consist of several electron-containing double bonds. The electrons of these fatty acids contribute to the formation of ROS and oxidative stress, thus causing a disruption in the flexibility of the spermatozoal membrane and diminishing the motility and sustainability of sperm <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. This may result in sperm membrane lipid peroxidation, DNA fragmentation, and apoptosis <ref name=PMID24675655><pubmed>24675655</pubmed></ref>. The following are a few antioxidants that have been proven to treat oxidative stress, hence improves male fertility.

'''1. Carotenoids'''
: Carotenoids are naturally occurring pigments produced by plants, algae, and photosynthetic bacteria <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. They can be divided into 2 different categories based on their chemical composition including carotenes that contain oxygen, and xanthophylls that only contain hydrocarbons <ref name=Higdon>Higdon, J., & Drake, V. (2009). Carotenoids | Linus Pauling Institute | Oregon State University. Lpi.oregonstate.edu. Retrieved 5 October 2015, from http://lpi.oregonstate.edu/mic/articles/dietary-factors/phytochemicals/carotenoids</ref>. The main source of these chemical compounds in the human diet are from fruits and vegetables as they give them their yellow, red and orange pigments. The role of carotenoids within the healthcare industry are forever growing as they have been suggested supplements for the human body, and as treatments for various cancers and possibly infertility disorders <ref><pubmed>12134711</pubmed></ref>. The antioxidant activity of carotenoids is performed by quenching (deactivating) singlet oxygen that is formed during photosnythesis by plants.
[[File:Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility.jpeg|300px|thumb|right|Proposed Mechanisms of Lycopene Treatment for Idiopathic Male Infertility]]

: '''Lycopenes''' are a type of carotene carotenoid that is found in various fruits and vegetables such as tomatoes and watermelon. Despite it being a source of vitamin A, it also possesses strong antioxidant properties as it is one of the most effective quenchers of singlet oxygen <ref name=PMID12899230><pubmed>12899230</pubmed></ref>. Although the exact mechanism of lycopenes is yet to be known, they have a role inneutralizing ROS and hindering their activity, achieved by their ability to donate an electron to free radicals <ref name=PMID19439288><pubmed>19439288</pubmed></ref>. As a result of this antioxidation pathway, lipid peroxidation is inhibited allowing for spermatozoal membranes to be retained and protected from further damage. Lycopenes have also been suggested to increase natural antioxidant enzymes indirectly, and also decrease the production of pro-inflammatory agents.

: '''Astaxanthin''' is a keto-carotenoid produced naturally from the microalgae ''Hematococcus pluvialis'' <ref>Willett, E. (2015). Studies Show Astaxanthin May Improve Sperm Health & Fertilization Rates. Natural-fertility-info.com. Retrieved 7 October 2015, from http://natural-fertility-info.com/astaxanthin-for-sperm-health.html</ref>. Due to its higher antioxidant activity in comparison to vitamin E, a fat solube antioxidant found in soybean and margarine, it has been suggested as an effective treatment and supplement for male factor infertility. An experimental trial to test Astaxanthin’s influence on sperm function was carried out in 2005 in 27 infertile men <ref name=PMID16110353><pubmed>16110353</pubmed></ref>. It was found that Astaxanthin allowed for the following:
*Increased motility concentration
*Improved sperm morphology and motility
*Decrease in ROS and Inhibin B (a regulator of spermatogenesis) levels

[[File:Model of the Activities of Cerium Dioxide Nanoparticles.jpeg|300px|thumb|right|Model of the Activities of Cerium Dioxide Nanoparticles]]
'''2. Cerium dioxide nanoparticles (CNPs)'''
: Cerium dioxide nanoparticles have been used extensively in the health care industry as potential pharmacological agents to treat various conditions from cancer to male infertility. These products are formed by cerium combining to oxygen obtaining a strong crystalline structure <ref name=Xu>Xu, C., & Qu, X. (2014). Cerium oxide nanoparticle: a remarkably versatile rare earth nanomaterial for biological applications. NPG Asia Materials, 6(3), e90. http://dx.doi.org/10.1038/am.2013.88</ref>. CNPs have the ability to interchange Ce 3+ and Ce 4+ ions that are present on its surface, leading to defects in oxygen within its crystal lattice structure. These regions on the surface of CNPs are ‘reactive sites’ to attract free radicals <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. A research team experimented on male rats to observe CNP effects on male health and infertility, providing further evidence that oxidative stress plays a key role in preventing proper spermatogenesis <ref name=PMID26097523><pubmed>26097523</pubmed></ref>. Therefore, the electronic structure of CNPs, and thus its antioxidant properties make this material a promising therapeutic for male infertility caused or affected by oxidative stress.

'''3. Vitamin E and C'''
: Vitamin E is a fat – soluble antioxidant that exists in 8 chemical forms of different biological activity. The only form of vitamin E required by the human body is alpha-tocopherol <ref name=Wen>Wen, J. (2006). The Role of Vitamin E in the Treatment of Male Infertility. Nutrition Bytes, 11(1), 1-6. Retrieved from http://escholarship.org/uc/item/1s2485fw</ref>. This chemical compound is found in various foods such as wheat germ oil, sunflower seeds and oil, and almonds <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Currently, the recommended dietary allowance (RDA) of vitamin E is 15 mg with an adult maximum of 1000 mg <ref name=National>National Institutes of Health,. (2013). Vitamin E — Health Professional Fact Sheet. Ods.od.nih.gov. Retrieved 7 October 2015, from https://ods.od.nih.gov/factsheets/VitaminE-HealthProfessional/</ref>. Due to the ability for vitamin E to prevent the peroxidation of PUFA, it has extremely positive implications on infertile men as spermatozoa have high levels of these compounds. From previous studies, vitamin E (alpha – tocopherol) levels decreased to 66.54% and 66.04% in oligospermic and azoospermic males respectively compared to fertile men <ref><pubmed>11225982</pubmed></ref>. Therefore there is a positive association between alpha – tocopherol levels and sperm count and motility .

: On the other hand, vitamin C is a water-soluble antioxidant <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. As an electron donor it neutralizes free radicals and also prevents ROS synthesis. As the human body does not produce or store vitamin C, daily intakes of vitamin C – containing foods are required to maintain its levels internally. Such foods with the highest vitamin C content include citrus fruits (oranges), kiwi fruit, broccoli and cauliflower. The RDA for vitamin C in male adults is 90mg/day <ref name=Evert>Evert, A., & Wang, N. (2015). Vitamin C: MedlinePlus Medical Encyclopedia. Nlm.nih.gov. Retrieved 7 October 2015, from https://www.nlm.nih.gov/medlineplus/ency/article/002404.htm</ref>. A study published in March 2015 demonstrated that infertile men administered with vitamin C had a significantly better sperm motility rate and morphology. Although it had little/no effect on sperm count, it is still a well recognizable and effective treatment for male infertility <ref><pubmed>26005963</pubmed></ref>.

====Traditional Chinese Medicine====

More recently discovered treatments for male infertility involve the hollistic principles of traditional Chinese medicine (TCM). Disregarding the conventional medicines more commonly prescribed in today’s society, the effects of Chinese herbal therapy, massage and acupuncture, have been suggested to improve sperm motility and viability of infertile males <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>. Acupuncture and massage has been proven to alleviate stress, increase blood flow to reproductive organs, regulate the immune system, and improve dysfunctions in male infertility <ref name=PMID23775386 ><pubmed>23775386</pubmed></ref>.

Additionally, Chinese herbal medicines have been widely used in experiments to prove their beneficial effects on treating infertility. The following are examples of a few herbal therapies that have been investigated.

'''Examples of Chinese Herbal Therapies'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Herb'''
! scope="col" width="500px"| '''Evidence'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Yi Kang Decoction'''
|style="height: 50px; background: #CCEEEE;"| 100 immune infertile males treated with this herb had greater sperm motility, agglutination, and overall increased pregnancy rates in comparison to prednisone, a steroid that reduces sperm antibody levels <ref><pubmed>16705853</pubmed></ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Hu Zhang Dan Shen Yin'''
|style="height: 50px; background: #EEEEEE;"| 60 treated infertile men showed a higher antisperm antibody reversing ratio than prednisone, thus allows for greater sperm production <ref><pubmed>16970170</pubmed></ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Zhibai Dihuang'''
|style="height: 50px; background: #CCEEEE;"| This herb was used to treat 80 cases of male immune infertility in the form of a pill, resulting in increased sperm motility and viability <ref><pubmed>25632744</pubmed></ref>
|}

===Surgical Treatments===

====Varicocele Surgery====

Varicocele repair can be performed by either percutaneous radiographic embolization or surgery to correct male infertility <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>. The desired outcome of these procedures is to lower the temperature of the scrotum for normal spermatogenesis to occur.

Percutaneous radiographic embolization involves the catheterization of the internal spermatic vein and its occlusion using a sclerosant (injectable irritant) or solid embolic devices such as stainless steel coils <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>. The administration of the sclerosant and solid embolic devices are given at the level of the inguinal crease and ligament respectively to prevent the backflow of blood into the pampiniform plexus. This method is much less invasive than surgical procedures and has very high success rates, and low recurrence rates <ref name=PMIDPMC2422968 ><pubmed>PMC2422968</pubmed></ref>.

As for the surgical approach, these methods are far more invasive but variable in terms of success rates and recurrence. It is important to note that all of these varicocele repair methods, surgery and embolisation, aim to impede increasing temperature of the scrotum caused by the pampiniform plexus.

'''Surgical Approach to Varicocele Repair'''
{| class="wikitable" style="text-align:center
|-
! scope="col" width="70px"| '''Surgical Method of Varicocele Repair'''
! scope="col" width="500px"| '''Description'''
|-
|style="text-align:center; background: #CCEEEE;"| '''Inguinal Surgery '''
|style="height: 50px; background: #CCEEEE;"|
*Involves opening the inguinal canal and the incision of the varicocele vein <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
*Allows preservation of lymphatic vessels
*Takes longer to heal
|-
|style="text-align:center; background: #EEEEEE;"| '''Subinguinal Surgery'''
|style="height: 50px; background: #EEEEEE;"|
*Incision below external inguinal ring
*Less pain due to the area of incision as it avoids the aponeurosis (flat tendon) of the abdominal external oblique muscle <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #CCEEEE;"| '''Retroperitoneal Surgery'''
|style="height: 50px; background: #CCEEEE;"|
*Ligation of the internal spermatic vein
*Can be performed as a mass ligation involving the artery, vein and lymphatic vessels, or artery sparing ligation preserving lymphatic vessels <ref name=Cocuzzo>Cocuzzo, M. Cocuzzo, M. A. Bragais, F. M/ P. Agarwal, A. (2008) The role of varicocele repair in the new era of assisted reproductive technologies. ''Clinics Vol. 63, No. 6'' retrieved 2nd September 2015, from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322008000300018&lng=en&nrm=iso&tlng=en</ref>
|-
|style="text-align:center; background: #EEEEEE;"| '''Laparoscopic Varicocelectomy'''
|style="height: 50px; background: #EEEEEE;"|
*At the level of the internal inguinal ring, the internal spermatic vein is ligated while sparing the corresponding artery <ref name=Tu>Tu, D., & Glassberg, K. (2010). Laparoscopic varicocelectomy. BJU International, 106(7), 1094-1104. http://dx.doi.org/10.1111/j.1464-410x.2010.09709.x</ref>
*Allows for a more accurate identification of vessels within the area
|}

====Ejaculatory Duct Resection====

Ejaculatory duct obstruction is a rare cause for infertile men. It is usually found in cases of severe oligospermia and azoospermia indicated by a low ejaculate volume and pH, and little or no fructose in seminal plasma <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. To correct this in the minority of infertility patients, transurethral resection of ejaculatory ducts (TURED) can be performed. Firstly, a digital rectal exam will show a cystic lesion or dilated ejaculatory duct. The duct is instilled with methylene blue dye to open the duct and confirm the resection is in the system <ref name=Schroeder>Schroeder-Printzen, I. (2000). Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach. Human Reproduction, 15(6), 1364-1368. http://dx.doi.org/10.1093/humrep/15.6.1364</ref>. A study by Yurdakul, Gokce, Kilic and Piskin, concluded that 11 out of 12 azoospermic males with complete ejaculatory duct obstruction who received TURED had sperm in their ejaculation <ref><pubmed>17899434</pubmed></ref>.

===Male Infertility Treatments with Assisted Reproductive Technologies (ARTs)===

It is known that males with fertility problems have little/no chance of conceiving a child with a woman. To address this issue many ARTs have been developed to allow for a successful pregnancy, which all involve the process of sperm retrieval.

====Intrauterine Insemination (IUI)====

====In Vitro Fertilisation (IVF)====

====Intracytoplasmic Sperm Injection (ICSI)====

Some ARTs allow for the male's genetic material to be passed onto the offspring, contingent upon a successful sperm extraction/retrieval such as intracytoplasmic sperm injection (ICSI). Although only a spermatozoon (single sperm) is required for this particular procedure, these treatment methods ultimately aim to "maximize the sperm retrieval yield" <ref name=PMID22958644><pubmed>22958644</pubmed></ref>.

==References==

<references/>

==External Resources==

File:Color Doppler ultrasonography of varicocele.jpeg

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==Color Doppler ultrasonography of varicocele==
Maximal venous diameters in the pampiniform plexus were measured during resting (A) and during a Valsalva maneuver (B) in the standing position.

===Reference===
<pubmed>25685302</pubmed>

===Copyright===
© The Korean Urological Association, 2015
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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File:Color Doppler ultrasonography of varicocele.jpeg

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<pubmed>25685302</pubmed>

2015 Group Project 4

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Z3463514: /* Diagnosis */

2015 Group Project 4

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Z3463514: /* Causes of Infertility */

2015 Group Project 4

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Z3463514: /* Causes of Infertility */

2015 Group Project 4

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Z3463514: /* Diagnosis */

User:Z3463514

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User:Z3463514

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Talk:2015 Group Project 4

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{{ANAT2341Project2015discussionheader}}

==Discussion==

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 11:20, 25 September 2015 (AEST) OK I discussed this with your group in last week's lab. you have not shown animal models, graphics, histology, media etc to really build your project page. The introduction does not give me a clear idea of the scope of the project. Not ready for peer review.

Hey guys, I have just had a really quick look on PubMed and I found a good starting article. Its a review article (I'm pretty sure) so I'm not sure if we can use it, but it discusses some interesting genetic causes of male infertility and also references a lot of primary articles.

PMID 26178295

--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 13:38, 25 August 2015 (AEST)

I can't seem to view anything but the first page of the article but the introduction gives a good idea on what male infertility is and how it arises. At the moment I have found 2 research articles that address factors that can increase male fertility. Although they do not address male infertility conditions specifically, in the discussion they imply that these methods can be applied to men who have them such as oligospermia and azoospermia. I feel as though we can use these articles when discussing alternative therapies for successful conception. Please have a read and share your opinions!

PMID 22958644 - note that you can only view the condensed version of this article

PMID 26097523 - you can view the whole article on biomed (subheadings in the discussion particularly addresses male infertility)

--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 14:17, 25 August 2015 (AEST)

Hey guys, it was pretty hard finding research articles from Pubmed regarding the epidemiology of male infertility. For now, I have found an article about sperm extraction which I thought could be an alternative for treatments. However I can't view the full article without paying, but the abstract from Pubmed seems to sum it up.
So, I came across a research article addressing the epidemiology and aetiology of male infertility, through Pubmed it doesn't have a direct link to the full PDF article however I linked it you guys on Facebook so have a read!

PMID 22128297

PMID 9663768

--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 11:59, 26 August 2015 (AEST)

Hello everyone! To get started, I just added a few headings on the page where you can add your research/review articles. Feel free to add more subheadings or change the wording of the titles - I'm sure we will need to as we research more. From looking at other groups' pages, I think it is also important we add a bit of 'Background Information" regarding the process of spermatogenesis and how any abnormalities can cause infertility so we can all look for articles as we go. Remember we are targeting this towards students like us, so a bit of key background info is essential.

--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 00:06, 27 August 2015 (AEST)

I just posted the articles that I found on male infertility. It was kind of hard to find ones because I stuck to studies in humans- but i found some good ones that were studies on rats (not sure if we can use them) and also some good secondary or review articles that we could use as background information maybe? So I'll just post the PMID's here..
* PMID 26303086
* PMID 23725463
* PMID 25160621
* PMID 25142466
--[[User:Z3462124|Z3462124]] ([[User talk:Z3462124|talk]]) 09:59, 27 August 2015 (AEST)

Not sure if we are review articles are any good, but I thought that it's also important to talk about "detecting abnormalities". I came across this review article which talks about the "male genital tract - colour dopple ultrasound" is a useful tool to detect impaired reproductive health.

PMID 25038770

--[[User:Z3463514|Z3463514]] ([[User talk:Z3463514|talk]]) 19:59, 27 August 2015 (AEST)

Good thinking! If anyone comes across more articles regarding this, please post them up! I'll add a 'diagnosis' sub-heading to the page

--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 22:23, 27 August 2015 (AEST)

Hey guys, found a couple of articles describing different methods of ARTs for male infertility:

These 2 talk about Intrauterine Insemination (IUI)
PMID 26294874
PMID 26288981

Also, another potential sub-heading to research might be the risks involved different ARTs
E.g. the following article about the prevalence of birth defects after a number of different male-related ARTs
PMID 26265143

--[[User:Z3462833|Z3462833]] ([[User talk:Z3462833|talk]]) 23:38, 27 August 2015 (AEST)

That sounds good. I think mentioning risks are important to show what is successful and what isnt. Feel free to add it under the "ART" heading (as a sub-heading)

--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 23:06, 31 August 2015 (AEST)

Hey I found this article that discusses some ARTs for infertile men. Its not a bad read and has info on two different methods, Intracytoplasmic morphologically selected sperm injection (IMSI) and conventional intracytoplasmic sperm injection (cICSI). You can read the full text on biomod

PMID 26307050

--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 17:27, 1 September 2015 (AEST)

LOOK!
This is a really good review article that talks about causes, diagnosis AND treatments. I recommend everyone to read it!

PMID 21243017

--[[User:Z3462297|Z3462297]] ([[User talk:Z3462297|talk]]) 11:09, 2 September 2015 (AEST)

==Peer Assessment==

User:Z3463514

2015-10-09T02:20:01Z

Z3463514:

User:Z3463514

2015-10-09T01:07:32Z

Z3463514:

2015 Group Project 4

2015-10-08T13:03:38Z

Z3463514: /* Background Information */