2015-10-23T01:01:44Z

Z3460352:

==Lab Attendance==
--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 13:45, 7 August 2015 (AEST)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 12:22, 14 August 2015 (AEST)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 13:33, 21 August 2015 (AEST)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 12:44, 28 August 2015 (AEST)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 12:04, 11 September 2015 (AEST)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 12:06, 18 September 2015 (AEST)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 14:03, 25 September 2015 (AEST)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 12:18, 9 October 2015 (AEDT)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 12:05, 16 October 2015 (AEDT)

--[[User:Z3460352|Z3460352]] ([[User talk:Z3460352|talk]]) 12:01, 23 October 2015 (AEDT)

==Week 1 Lab Assessment==

'''''Chromosomal Development in relation to Blastocyst Morphology'''''

Figueira, Setti, Braga, Laconelli and Borges aimed to decipher the link between embryo morphology and chromosomal development in the early days of fertilisation. Specifically, the study focused on the structure of chromosomes within the embryo at day three of development.

For the purpose of the experiment, Intra-Cytoplasmic Sperm Injection (ICSI) cycles were run 106 times, before a genetic screening test was completed (PGS, Pre-Implantation Genetic aneuploidy Screening). This presented 596 embryos for use. Embryonic growth was monitored closely and the genetic composition of each cell was analysed. Fluorescent In Situ Hybridisation (FISH) was used to analyse the complementary sequences of DNA within the embryos; 200 of the 564 tagged had developed into blastocysts.

Approximately 59% of the blastocysts were euploid (having an even set of chromosomes), whereas a lesser proportion of embryos that had not become blastocysts were euploid (41.2%).
Furthermore, abnormalities in blastocyst development were observed, finding that if an embryo was an euploid, it would most likely have a normal inner cell mass (ICM). In contrast, aneuploid embryos (those with an abnormal set of chromosomes, generally 45 or 47) were found to be those with abnormal ICMs. A similar conclusion was found in the observation of trophectoderm morphology in that euploid embryos had a ‘normal’ cell distribution, whereas aneuploids did not.

Based on these findings, the study concluded that embryo development is not hindered by genetic abnormalities in the early stages of development. However, ICM morphology presents a stronger link to chromosomal abnormalities as the majority of aneuploidy embryos had irregular ICMs. Although this study presented clear links between embryonic development and genetic abnormalities, further studies could be conducted to strengthen these connections.

PMID 26246880

Reference <ref>
<pubmed>26241855</pubmed></ref>

'''''In Vitro Fertilisation in women with, and without Polycystic Ovarian Syndrome'''''

This study, completed by Siristatidis, Sergentanis, Vogiatzi, Kanavidis, Chrelias, Papantonious and Psaltopoulou, was aimed at evaluating the outcomes of In Vitro Maturation (IVM) in women with polycystic ovarian syndrome (PCOS) versus women without PCOS, undergoing In Vitro Fertilisation (IVF). Past studies were utilised by the researchers for comparison, and were kept strictly to human experiments (not animals). Possible IVF outcomes across these studies were compared, including implantation, clinical pregnancy, cycle cancellation, oocyte maturation, oocyte fertilisation, live birth or miscarriage, in both PCOS and non-PCOS individuals. A large emphasis was placed on the number of successful births per patient, per cycle.

Due to the fact that the sources collected in this study were qualitative in nature, the researchers employed the Newcastle Ottawa Quality scale. This is a nine item scale used to analyse the experiments of interest, and to organise them into order of reliability. Additionally, confidence interval and statistical analysis schemes (using 95% confidence intervals and STATA Software, respectively) were developed to further evaluate the pattern of live births and clinical pregnancies. A total of eleven studies were examined; 268 PCOS (328 cyles), 100 PCO (110 cycles) and 440 control (480) women were involved.

It was found that when PCOS patients were administered with both follicle stimulating hormone (FSH) and hCG, a higher rate of clinical pregnancies was observed. In the absence of hCG, the birth rates did not differ across the three groups. The experiments were organised into two groups; a cycle study and a women's study. In the cycle study, live birth rates did not differ greatly between the PCOS and non-PCOS groups, whereas in the women’s experiment, the birth rate for PCOS patients was slightly higher. When comparing the cycle and women’s experiment, once again PCOS patients presented greater birth and implantation rates. PCOS patients only presented lower rates than non-PCOS individuals in the fertilisation and cancellation studies. In terms of miscarriages, the rates were consistent across all three groups.

This study is significant in that drew upon the work of numerous researchers from various years, comparing their reliability and conclusions. Generally, it was found that more recent studies were of greater reliability, and therefore presented a higher score on the Newcastle Ottawa Quality scale. Siristatidis ''et al.'' came to the conclusion that IVM has a positive impact on the birth rate of PCOS women, in comparison to non-PCOS patients.

PMID 26241855

Reference <ref>

<pubmed>26246880</pubmed></ref>

_______________________________________________________________________________________________________________________________________________________________________________________________________________

<references/>

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 19:21, 27 August 2015 (AEST) these are good summaries of these papers. You could try and format the pubmed reference correctly by having ll on the same line. (5/5)

==Week 2 Lab Assessment==

{{Uploading Images in 5 Easy Steps table}}

[[File:Sex Determination Across Species.jpeg|300px]]

<pubmed>24983465</pubmed>|[http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001899 PLoS Biol.]

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 19:21, 27 August 2015 (AEST) Image uploaded correctly with all required information. Note when added to your own page you require <nowiki><ref></ref></nowiki> tags outside the PubMed ref to have it appear correctly. You had also left the 2 off the PMID, I have added it here, so the correct reference now appears, check the reference matches and number next time. (5/5)

==Week 3 Lab Assessment==

--[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 19:21, 27 August 2015 (AEST) These references relate to your group project. (5/5)
'''TREATMENT OF FEMALE INFERTILITY (Group 3)'''

'''''The Effect of a Complex Multi-modality Ayurvedic Treatment in a Case of Unknown Female Infertility'''''

This article documented a 38 year old woman's journey to giving birth, after she was advised that she was infertile (of unknown cause). The researchers detail the various modern day medical treatments she underwent to become pregnant, all of which were unsuccessful. She then decided to try holistic medicine in the form of Ayurvedic treatment, which consisted of meditation, a controlled diet and yoga. To the researchers' surprise, she became pregnant soon after, and gave birth to a healthy baby boy in 2012. The study comes to the conclusion that Ayurvedic medicine and successful birth rates do not show a strong correlation, and thus should not be favoured over standard medical treatments. However, they did state that holistic medicine could improve the overall wellbeing of the mother (in terms of stress and diet), which in turn increases the chances of becoming pregnant.

<pubmed>26278074</pubmed>
* * *
'''''Pregnancy Rate after Controlled Ovarian Hyperstimulation and Intrauterine Insemination for the Treatment of Endometriosis following Surgery'''''

This study investigated various treatments available for women with endometriosis, and the rate of successful pregnancies and births in patients following their treatment. The researchers came to the conclusion that a woman's chances of becoming pregnant increased following laparoscopic surgery, particularly in the first six months following the procedure. If pregnancy does not occur, controlled ovarian hyperstimulation and intrauterine insemination (COH-IU) should be the next option, due to its success rates.

<pubmed>26247014</pubmed>
* * *

'''''Time-limited Hydrotubation Combined with Clomiphene Citrate Treatment for Unexplained Infertility'''''

In this experiment, 80 random patients with "unexplained inferility" were selected and treated with hydotrubation and clomiphene citrate (CC). Of the 80 patients, 15 became pregnant, with the researchers concluding that combined hydrotubation and CC treatment increased a woman's chance of becoming pregnant to a greater degree than just CC alone. Further tests need to be completed to strengthen the correlation between the treatment and outcome.

<pubmed>26152000</pubmed>
* * *

'''''Frequency and Outcome of Treatment in Polycystic Ovaries Related Infertility'''''

This study examined treatments available to women with Polycystic Ovarian Syndrome (PCOS). It came to the conclusion that in overweight women with PCOS, weight loss, exercise and better lifestyle choices are the best treatments as they significantly increases pregnancy rates. Furthermore, clomiphene citrate (CC) and metformine combined treatments are highly effective in PCOS women, and should be one of the first options offered to a patient.

<pubmed>26150870</pubmed>

==Week 4 Lab Assessment - ''Quiz''==

<quiz display=simple>

{Select the statement that is '''MOST CORRECT''' with regards to grastrulation.
|type="()"}
- The ectoderm and mesoderm are both epithelial layers, with the endoderm contributing connective tissue.
- The columnar epithelial layer of the ectoderm later forms blood vessel and muscle tissue.
+ The mesoderm and endoderm both contribute to the gastrointestinal and respiratory tracts.
- A layer of connective tissue (mesoderm) is sandwiched between a columnar epithelial layer (endoderm) and a cuboidal epithelial layer (ectoderm).
|| '''The mesoderm and endoderm are the two layers that contribute to the GIT and respiratory tracts. The ectoderm (columnar epithelium) and endoderm (cuboidal epithelium) sandwich a layer of connective tissue (mesoderm).'''

{Select the '''incorrect statement''' regarding embryonic vascular development.
|type="()"}
- Embryonic red blood cells are often nucleated.
+ Fetal haemoglobin takes the same form as adult haemoglobin due to a high demand for oxygen during development.
- During heart looping, the ventricles begin at the top of the tube before the atria begin to ascend.
- The heart originates from the mesoderm at the cranial end of the neural tube.
||'''Fetal haemoglobin is not the same as adult haemoglobin. Oxygen demand is actually less during fetal development, and the pattern of gaseous exchange differs largely to that of a developed individual.'''

{In the maternal placenta, fibrin-type fibrinoid is said to replace which of the following types of cells?
|type="()"}
+ Degenerative syncytiotrophoblasts
- Extravillous trophoblasts
- Fibroblasts
- Epithelial cells
|| '''Degnerative syncytiotrophoblasts are replaced by fibrin-type fibrinoid material; extravillous trophoblasts secrete matrix-type fibrinoid. Epithelial cells and fibroblasts are not involved in fibrinoid replacement.'''

</quiz>

{| border='0px'

[[Category:Quiz]] [[Category:Medicine]] [[Category:Foundations]]

==Week 5 Lab Assessment==

'''What is the difference between gastroschisis and omphalocele?'''

Gastroschisis is a defect characterised by an extra-umbilical herniation of the bowel, with the absence of a sac covering anteriorly. The condition is due to amniotic damage that may arise from exposure to a particular toxin or from poor vascular supply to the abdominal wall (on the right). Conversely, mesenteric injury can also give rise to the condition, which appears once in every 600 births.

In contrast, omphalocele occurs much less frequently; 1 in every 3,000-10,000 births. The condition results from an umbilical ring defect ventrally, causing abdominal viscera herniation. Herniation is persistent in the midgut, causing umbilical vessels to insert onto the sac and circle it. Characteristics of omphalocele include the absence of skin, fascia and abdominal muscles because of the incorrect fusion of parts of the abdominal wall.

Gastroschisis can occur at the 6-7 week point of development, whereas omphalocele arises at the 9 week mark. The former can be treated surgically, with normal bowel motility being restored once the child is born. Conversely, endoscopy and pH monitoring are the primary forms of treatment used for omphalocele, with constant medical check ups if the condition persists.

<pubmed>PMC3024424</pubmed>

<pubmed>PMC4515833</pubmed>

==Week 6 Lab Assessment==

'''''Group Work'''''

==Week 7 Lab 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.'''

Two tissues give rise to the pituitary gland; ectoderm and neuroectoderm. The former lines the stomodeum, which grows into the primary oral cavity and becomes completely lined with ectoderm (containing features of neural origin). The prosencephalon is located superior to the stomodeum, extensions of Meckel’s cartilage laterally and protuberances of the cardiogenic area inferiorly. In the oral-pharyngeal ectoderm in front of the buccopharyngeal membrane, Rathke’s pouch begins to form. Some pituitary cells also grow in this region, with contributions from the neural plate. The pouch continues to grow in a dorsal direction and will eventually join the infundibulum. This fusion causes the development of pouch epithelium, pars intermedia and the pars distalis. The remainder of the pouch will become the anterior pituitary.

At this point in development, various transcription factors intervene. They induce cell proliferation and apoptosis, as well as gene activation, which further induce neural cell development. The excretion of growth hormone, follicle stimulating hormone and luteinising hormone commence, which are vital in the remaining development of the embryo (in terms of metabolism, growth and homeostasis).

<pubmed>25858531</pubmed>
PMID 25858531

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

* Ectoderm of pharangeal arch 1

* Neural crest:
--> Ectomesenchymal cells
--> Odontoblasts (a type of mesenchymal cell) differentiate into predentins, and then calcify into dentins.
--> Ameloblasts produce enamel and hold tooth to bone socket.

<pubmed>19266065</pubmed>
PMID 19266065

==Week 8 Lab Assessment==

'''''Group Project'''''

==Week 9 Lab Assessment - ''Peer Reviews''==

'''GROUP 1'''

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!

* * *

'''GROUP 2'''

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.

* * *

'''GROUP 4'''

Probably the most enjoyable page to read, thus far.

'''COMMENDATIONS'''

• Great introduction; straight to the point and easy to understand.

• Your information is organised under appropriate subheadings, making your page easy to read and follow.

• Your “Types of Male Infertility” table is great! You have provided clear definitions of each condition and the use of colour makes the information stand out.

• Appropriate referencing throughout.

• Great audio-visual sources, especially the video.

• Your page looks even better than a Wikipedia page! A lot of time and effort has gone into it.

'''RECOMMENDATIONS'''

• A glossary at the end of the page would be great, even though you have explained a lot of the concepts in your text. This way the reader does not have to skim through your page to find a term and they can go straight to the glossary.

• Information under IVF and IUI is absent in “Male Infertility Treatments.” I am not sure if these were meant to be deleted or text will be added later.

It is evident that you have worked fantastically as a team and you have done a lot of research. Each topic is covered comprehensively and aided by a table, image or diagram, making the topic more appealing to the reader. Well done!

* * *

'''GROUP 5'''

'''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.

* * *

'''GROUP 6'''

'''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!

______________________________________________________________________________________________________________________________________________________

{{StudentPage2015}}

2015 Group Project 3

2015-10-23T00:58:18Z

Z3460352:

{{ANAT2341Project2015header}}

=Polycystic Ovarian Syndrome=

[[File:Polycystic Ovary juxtaposed with a Standard Ovary.png|700px|thumb|centre|PCOS Ovary vs. Non-PCOS Ovary]]

===Introduction===

[[File:Prevalence of Primary Infertility in 2010.jpeg|400px|thumb|right|Prevalence of Primary Infertility in 2010]]

Female Infertility refers to the failure to conceive after one year of regular unprotected intercourse in females <ref name=one><pubmed>26150870</pubmed></ref>. In 2010, infertility affected 48.5 million couples world wide and the areas of highest prevalence included North Africa and Middle East, South Asia, Central/Eastern Europe and Central Asia and Sub-Saharan Africa <ref name=two><pubmed>23271957</pubmed></ref>. As there are several causes of female infertility, we will be focusing on infertility that is caused by '''Polycystic Ovarian Syndrome''' (PCOS), the most common cause of infertility that is medically treatable <ref name=one/>.

{|
|-bgcolor="DDCEF2"
|
* '''Polycystic Ovarian Syndrome (PCOS) is a common endocrine disorder, affecting up to 20% of reproductive aged women <ref name=hey><pubmed>21896560</pubmed></ref>. It is the most common cause of anovulatory infertility <ref name=one/> which refers to infertility caused by the the absence of ovulation.'''
|}

=Causes=

PCOS is a disorder of heterogeneous origin with unknown aetiology <ref name=hey/>. Studies have shown that both genetic and environmental factors contribute to the development of PCOS in women however there is limited research into the actual interactions between these two factors <ref name=un><pubmed>17185788</pubmed></ref>.

===Genetic Factors===

Despite the lack of information regarding its aetiology, there is increasing evidence for a genetic involvement in the endocrine disorder. Studies have shown that genes play an important role in contributing towards the clinical and biochemical features of the disease. This evidence includes the family clustering of cases, greater unanimity between monozygotic twins than heterozygotic twins and the ability to inherit endocrine and metabolic features of PCOS <ref name=hey/>.

In one study, 115 sisters of women with PCOS were examined and results showed that half of these sisters had high testosterone levels, suggesting that hyperandrogenemia is a common trait with a dominant pattern of inheritance. These results strongly supported the idea of the familial clustering of biochemical features such as hyperandrogenism in first degree relatives <ref name=deux><pubmed>9843997</pubmed></ref>.

Several genes have been considered to play an important role in the development of PCOS such as CYP11A, the insulin gene, the follistatin gene and a region near the insulin receptor gene. Yet, the evidence supporting most of these genes has been refuted by larger studies, except for the region near the insulin receptor gene <ref name=deux/>. Among these, the gene CYP11a is the one that is strongly associated with hyperandrogenism in women with PCOS. <ref name=cinq><pubmed>9147642</pubmed></ref> While it doesn't isolate this gene as the sole cause of PCOS, variation of the genotype at this locus contributes to production of excess androgen <ref name=h4><pubmed>7962289</pubmed></ref>.

Studies have also shown that there is strong evidence for linkage between the alleles at the Variable Number Tandem Repeats (VNTR) which is situated 5' to the insulin gene and PCOS. The data from the study suggests that it is a very susceptible region in PCOS and also may play a role in the development of hyperinsulinaemia <ref name=trois><pubmed>9455828</pubmed></ref>.

===Environmental Factors===

The prevalence of PCOS in populations where there has been a constant gene pool indicates that environmental factors play a significant role in the aetiology of PCOS <ref name=un/>. The role of environmental factors in PCOS has been extensively investigated through family studies, especially in sisters in order to minimise the effect of genotype on the PCOS phenotype <ref name=deux/>.

====Obesity and Diet====

[[File:Graph.jpg|600px|thumb|right|BMI for different PCOS phenotypes]]

Obesity is the major environmental factor driving the development of PCOS in susceptible individuals. The rising rates of PCOS have been paralleled by the widespread emergence of obesity and type 2 diabetes which are prevalent in developed countries,<ref name=un/>. Several family studies have shed light on the role of obesity in PCOS developpement, primarily one which studied the phenotypic characteristics among PCOS sisters <ref name=deux/>. It was found that sisters with hyperandrogenemia and irregular cycles had higher body weights than those with regular cycles and hyperandrogenemia. These findings were supported by another study which reported that affected sisters had higher body weights than unaffected ones <ref name=green><pubmed>11994352</pubmed></ref>. The role of obesity in the intrauterine environment was also shown to be important after studies suggested that PCOS women with increased weight at birth were associated with overweight mothers <ref name=blue><pubmed>9343501</pubmed></ref>.

The risk of developing PCOS from obesity is compounded by poor dietary choices and lack of physical activity which has begun to characterise the lifestyle in developed countries <ref name=deux/>. Energy dense food and larger sizes in portion act as major contributors towards the increasing incidence of obesity. The quality and type of nutrition can also have an effect on the PCOS phenotype while interacting with different genotypes <ref name=un/>.

====Medication====

Studies have shown that valproic acid in medication used to treat epilepsy and bipolar disorders contributes to the development of PCOS. Women with these disorders may develop the typical features of PCOS such as polycystic ovaries, anovulation, hyperandrogenism and obesity <ref name=quartre><pubmed>8413434</pubmed></ref>. Recent studies also suggest that the weight gain from medication is significant as it can lead to the development of PCOS <ref name=deux/>.

=Pathogenesis=

===Cyst Formation===

The pathogenesis of polycystic ovarian syndrome is poorly understood, however it is believed that insulin resistance and excess androgens such as testosterone play a fundamental role. The below image details the various types of cysts that can form in the ovary and uterus. In PCOS patients, cysts arise due to irregular periods, and thus an imbalance of hormone levels. <ref> Mayo Clinic Staff '''Ovarian Cysts Causes''' 13th August 2014 Date Retrieved: 22nd October 2015. http://www.mayoclinic.org/diseases-conditions/ovarian-cysts/basics/causes/con-20019937 </ref>

[[File:Types of Cysts.jpg|700px|thumb|centre|Types of Ovarian Cysts]]

Underlying factors such as obesity and genetic predispositions likely contribute to the onset of polycystic ovarian syndrome through the development of a combination of hyperinsulinemia and hyperandrogenemia.<ref name=eleven><pubmed>PMC4556908</pubmed></ref>

===Hyperinsulinemia===

Hyperinsulinemia is a term that defines the presence of excessive amounts of insulin in the blood relative to the amount of glucose. <ref name=fourteen><pubmed>PMC4114053</pubmed></ref> This phenomenon is typically associated with obesity and excess adipose tissue, both of which are associated with insulin resistance. In order to overcome this resistance, insulin secretion is increased in an attempt to normalise blood glucose levels, thereby leading to hyperinsulineamia. <ref><pubmed>PMC2782313</pubmed></ref> Excessive levels of insulin typically cause disruption to the hypothalamus-hypophysis-ovary axis whilst insulin resistance in ovarian tissues leads to decreased metabolic signalling. However, steroidogenic activity is largely unaffected by the impaired metabolic signalling, thereby paving the way androgens to become more effect and paving the way towards hyperandrogenemia. <ref><pubmed>PMC4334071</pubmed></ref>
[[File:Patholophysiology of Polycystic Ovarian Syndrome.jpg|700px|thumb|left|The impact of hyperinsulinemia and hyperandrogenemia on the development of polycystic ovarian syndrome]]

===Hyperandrogenemia===

Hyperandrogenemia is a hallmark of the development of polycystic ovarian syndrome, with 80% of women presenting with excess androgen also having polycystic ovaries.<ref><pubmed>PMC3872139</pubmed></ref> The disruption of the hypothalamus hypophysis ovary axis as a result of hyperinsulinemia increases the release of GnRH and LH, leading to increased androgen production in the ovarian theca cells. Hyperandrogenemia decreases the feedback sensitivity of both estradiol and progesterone within gonadotropic hypothalmic cells. <ref><pubmed>PMC4334071</pubmed></ref> A deficiency of FSH is observed and correlates with the increased secretion of Gonadotrophin-releasing hormone (GnRH) and Luteinizing hormone (LH). As a result of this deficiency, graunlosa cell aromatisation to oestrogens as well as follicle maturation and ovulation will be drastically impaired. <ref><pubmed>PMC3453528</pubmed></ref>

As a consequence of the impairment of follicle maturation, small antral follicles will accumulate within the periphery of the ovary and develop a cystic morphology. Ovulation will be unable to occur due to the absence of mature follicles, culminating in infertility. <ref><pubmed>PMC4562327</pubmed></ref>

===Hyperandrogenism===

====Animal Models====

Studies conducted on female rhesus monkeys have supported evidence for the foetal origins of the clinical features of PCOS <ref name=h1><pubmed>18406243</pubmed></ref>. It has been shown that in human females, an excess of androgen exposure at any stage from the development of the ovaries to the onset of puberty manifests as characteristic features of PCOS, such as resistance to insulin and LH hypersecretion. After exposure to levels of testosterone matching those of fetal males, in utero, female rhesus monkeys were found to display the clinical and biochemical features typical of PCOS such as hypersecretion of LH and abnormal insulin action. These results correlated to those of similar studies conducted on sheep, where the pregnant ewe was exposed to excessive levels of testosterone and LH secretion and abnormality in ovarian cycles were again prominent features <ref name=sheep>Padmanabhan V, Evans NP, Taylor JA, Robinson JE1997 '''Prenatal exposure to androgens leads to the development of cystic ovaries in the sheep'''. Biol Reprod 56:194</ref>. While these studies indicate that similar biochemical and clinical manifestations in humans originate from excess androgen exposure of the female fetus, it must be noted that it is very unlikely for any excess androgen production to be passed across the placenta from the mother to her daughter. This is because mechanisms such as androgen binding proteins and placental metabolism of androgen prevent excess androgen entering the circulation of the fetus <ref name=h2><pubmed>12098657</pubmed></ref>.

====Cell Culture Models====

While studies have shown that the adrenal could be a source of excess androgen such as the adrenal <ref name=h3><pubmed>7962325</pubmed></ref>, they were followed by various studies using cell culture models which demonstrated that the ovary was the major source of excess androgen <ref name=h4/> <ref name=h5><pubmed>9302378</pubmed></ref>. ''In vitro'' studies have shown that the production of steroids is abnormal in theca cells <ref name=h3/>. In women affected by PCOS, stimulation by human chorionic gonadotrophin (hCG) is followed by an increase in thecal steroid production after suppression of LH by a GnRH analogue <ref name=h5/>. Theca cells cultured from polycystic ovaries produce 20 times as much androstenedione as those from normal ovaries <ref name=h4/> with increased expression of mRNA for enzymes responsible for making steroids also reported in following studies. <ref name=h6><pubmed>10852468</pubmed></ref> These results have prompted many studies on genes encoding these steroidogeneic enzymes.

[[File:Polycystic_rat_ovary.jpg|500px|thumb|right|An example of polycysts present in the polycystic ovaries of a rat specimen]]

=Signs and Symptoms=

The symptoms of PCOS are different for each women. The three cardinal signs of PCOS are hyperandrogenism, polycystic ovaries and ovarian dysfunction <ref name=sign1><pubmed>14688154</pubmed></ref>. Common clinical symptoms include <ref> Women's Heath, U.S. Department of Health and Human Services ,[ http://www.womenshealth.gov/publications/our-publications/fact-sheet/polycystic-ovary-syndrome.html#d ], 'Polycystic ovary syndrome (PCOS) fact sheet'</ref> ;

{|
|-bgcolor="DDCEF2"
|
* Infertility- due to anovulation.
* Irregular Menstrual Cycles
* Hirsutism
* Ovarian Cysts
* Obesity
* Male Pattern Baldness
* Skin Tags
* Pelvic Pain
|}

Along with obesity, PCOS is also associated with other metabolic issues such as insulin resistance, hyperinsulinemia and type 2 diabetes mellitus. It has also been associated with cardiovascular problems and cancers of the breast and endometrium <ref name=sign3><pubmed>PMC4341818</pubmed></ref>.

=Diagnosis=

A major diagnostic tool for PCOS is a pelvic ultrasound, but PCOS diagnosis cannot be completely dependent on just pelvic ultrasounds. A patient with PCOS may not necessarily have polycystic ovaries, and those with ovarian cysts may not necessarily have PCOS. A range of diagnostic assessments and associated symptoms have to be thoroughly investigated.

===Medical history and examination===
Clinical questions are asked or filled out in the form of a questionnaire to assess and assist in the diagnosis of PCOS. Studies show that those with a history:
*infrequent and irregular menstruation
*hirsutism (related to high levels of androgens in the blood – hyperandrogenism)
*obesity
*acne production
are at a higher predictive risk of PCOS. But questions regarding failed pregnancy attempts and history of nipple discharge proved no correlation in diagnosing PCOS. <ref> <pubmed> 17872783 </pubmed> </ref>

[[File:Ultrasound of Polycystic Ovaries .jpg|400px|thumb|right|Ultrasound of Polycystic Ovaries]]

===Blood Test===
A patient with elevated levels of androgens, a medical condition called hyperandrogenism, is very highly likely to have PCOS. <ref> <pubmed> 20591140 </pubmed> </ref>
Androgens, such as testosterone, and free androgen index (FAI) are the two tests best used in diagnosing hyperandrogenism.
Androgen excess in PCOS is a result from increased synthesis and release of ovarian androgens. Dehydroepiandrosterone sulfate (DHEA-S) levels are used as a biomarker for testing androgen levels, as it is made exclusively by the adrenal glands. DHEA-S levels of above 1890 micromol/L is extremely suggestive of hyperandrogenism. <ref> <pubmed> 18844715 </pubmed> </ref>
Free androgen index (FAI) is the ratio of total testosterone measurement to levels of sex hormone-binding globulin (SHBG). Those with PCOS will have high FAI, as this indicates a high ration of free testosterone in the body.
Other blood tests are also done to help exclude other predisposing factors such as levels of Thyroid Stimulating Hormone (TSH) and Follicle-stimulating hormone (FSH). An elevated ratio of LSH to FSH, of above 2:1 <ref> <pubmed> 14737959 </pubmed> </ref>, indicates a possibility, but not definitively, of PCOS.
The effect of insulin on blood can also be tested for insulin resistance. Insulin resistance enhances androgen production and increases free androgen levels by reducing SHBG. This can used as an indication marker for the possibility of PCOS
A study in 2014 showed that Anti-Müllerian hormone (AMH) is found to be elevated in patients with PCOS <ref> <pubmed> 24821925 </pubmed> </ref>, giving rise to its potential clinical implication in diagnosing PCOS. AMH is exclusively produced in ovarian follicles, with individual AMH concentration reflecting the quantity of remaining primordial follicles and measure of ovarian reserve.

===Gynecologic ultrasonography===

Gynecologic ultrasonography is a pelvic ultrasound, specifically to the female pelvic region, with regards to the uterus, ovaries and the fallopian tube. The examination can be performed by transabdominal ultrasonography, with a full bladder, or transvaginal ultrasonography with a vaginal transducer. Typically transvaginal imaging shows a better and clearer image than transabdominal ultrasonography, as it uses higher frequency imaging, but is limited to areas it can reach. In the case of PCOS, both techniques can provide an image of the ovaries. Studies suggest that if more than 25 follicles are seen in an ovary, predominantly in the periphery, in women between 18-35 years, it is described to have a polycystic ovarian morphology. <ref> <pubmed> 24345633 </pubmed> </ref>

===Magnetic Resonance Imaging===
Ovaries can also be seen on MRIs. On MRIs, PCOS is characterized by numberous peripheral cysts where the ovaries affected to be slightly larger than normal. Although MRI is seen to be effective in ovarian imaging, the finding of peripheral ovarian cysts in MRIsmay not be PCOS specific. <ref> <pubmed> 8888256 </pubmed> </ref> But studies have seen that MR imaging in adolescence uncover distinct differences between young patients with and without PCOS <ref> <pubmed> 23292744 </pubmed> </ref>, with also great diagnostic sensitivity with patients between the age of 21-30 <ref> <pubmed> 19241321 </pubmed> </ref>, providing assistance of imagery in patients whom may be opposed to transvaginal ultrasounds.

=Prevention and Treatment=

There currently is no cure for PCOS, nor can it be prevented. This can be largely attributed to genetics, and because it can progress without being noticed for an extended period (generally until puberty begins). Treatment maybe involve lifestyle changes or hormonal augmentation in regulating periods, hirsutism, and acne, in addition to regulating androgen levels.

===Current Treatments===

{|border="1"
|-bgcolor="DDCEF2"
| '''CURRENT TREATMENT'''
| '''DISADVANTAGES'''
|-
| General Practitioners tend to prescribe oral anti-oestrogens, most commonly the contraceptive pill, to restore ovulation.
| This method only has a 50% success rate in PCOS patients. It does not directly increase fertility rates, but restores the menstrual cycle. <ref name= pink><pubmed>26194691</pubmed></ref>

|-bgcolor="FAF5FF"
| Lifestyle changes are highly encouraged by medical practitioners. Diet and exercise regimes can be designed with a dietitian or nutritionist. <ref name= purple><pubmed>26289303</pubmed></ref>
| Exercise and diet plans do not directly increase fertility. They are designed to enhance weight loss, which in some patients can encourage normal hormone levels from the pituitary and thyroid. <ref name=purple/>

|-
| Clomiphene citrate administration (generally in pill form, as prescribed by a GP). Such pills stimulate the pituitary gland to release GnRH to simulate ovulation (with a 72% success rate). <ref name= green><pubmed>26150870</pubmed></ref>
| Clomiphene can cause multiple side effects, most notably abnormal uterine bleeding and pelvic pain to due enlargement of the ovaries.

Thus, it cannot be as frequently prescribed as the contraceptive pill, and careful patient monitoring is imperative <ref name=green/>.

|-bgcolor="FAF5FF"
| Higher fertility rates are observed in treatments combining clomiphene citrate and metformin (79% success) <ref name=green/>.
| Similar disadvantages as clomiphene, above.
|}

'''Note that the success rates for current PCOS treatments vary between patients. Some individuals may require more than a simple diet and exercise plan and may need various medicines and even ovarian drilling (detailed below) to encourage fertility. Oral contraceptives do not have a significant impact on fertility rates, but rather regulate the menstrual cycle and in turn, hormone levels (oestrogen and progesterone).'''

===Laparoscopic Ovarian Drilling===

Laparoscopic Ovarian drilling (LOD) is a surgical method of treating polycystic ovaries and is typically used when an infertile woman does not respond to administration of clomiphene citrate. <ref name=blue><pubmed>PMC4367066</pubmed></ref>. The most common form of LOD involves electrocautery through the use of an insulinated uniupolar needle electrode. The exact method of action of LOD is poorly understood. The most accepted hypothesis however is that the breakdown of ovarian follicles and stroma via heat, laser or mechanical drilling brings about a decrease in androgen and inhibin levels, followed by a rise in the levels of FSH. Inflammatory growth factors produced in response to the thermal injury caused by laser drilling can enhance the action that FSH has on folliculogenesis. Improved blood flow often results from LOD which serves to drastically improves the delivery of gonadotrophins to the ovary.<ref name=blue><pubmed>PMC4367066</pubmed></ref>.

LOD can be an appealing alternative to treatment with gonadotrophins, as the latter is typically time consuming, expensive and requires constant monitoring in order to be effective.<ref><pubmed>22696324</pubmed></ref>

The overall effectiveness of LOD as a standalone treatment for PCOS is still questionable. Several studies have shown that there is no evidence of significant differences in pregnancy and live births in women undergoing LOD and those undergoing other medical treatments. <ref name=blue><pubmed>PMC4367066</pubmed></ref>.

<html5media height="300" width="400">https://www.youtube.com/watch?v=JH-Yx1QWUBk</html5media>

Ovarian Drilling by Laparoscopy for PCOS <ref>Mishra, R., (2014, September 8) Ovarian Drilling by Laparoscopy for PCOS. Retrieved from https://www.youtube.com/watch?v=JH-Yx1QWUBk</ref>

===New Trials===

Some studies have found that regular Selenium supplements can encourage fertility among PCOS patients. The program, which is still in its early trial period, requires women to consume selenium tablets for 8 weeks. This study has found a significant decrease in dehydroepiandrosterone (DHEA) levels in patients, thus reducing excessive hair growth associated with PCOS. A direct link to increased fertility is yet to be established, and thus further testing is required.<ref><pubmed>26267328</pubmed></ref>

=PCOS and Conceiving=

Although PCOS can significantly hinder a woman's chances of conceiving, many women with the condition do give birth to healthy children. This is largely due to modern day medical treatments, as detailed above. The following is a blog post written by 'Tarryn,' the founder of PCOS Diet Support (www.pcosdietsupport.com):

[[File:Tarryn & PCOS Diet Support.jpg|400px|thumb|left|Tarryn and her daughter, after she overcame her PCOS with various treatments.]]

''I’m Tarryn and I was diagnosed with PCOS in January 2010. I always suspected something was amiss as my menstrual cycle has always been irregular. In 2001 or 2002 I consulted a Gynaecologist who did an ultrasound and told me that I don’t ovulate every month and put me on the pill. He made no mention of PCOS.''

''When hubby and I decided to start trying for a baby in 2009, I just knew something was wrong. So, I went to my doctor who did some blood tests and diagnosed me with PCOS. Although I had my suspicions already, I was devastated.''

''I decided I had to do something and went on a low GI diet and exercised regularly. I fell pregnant 9 months later. I had been taking my basal body temperature every morning and the only time I ovulated in 9 months, I fell pregnant with our beautiful daughter.''

''Toward the end of 2012, we decided we’d like to give our little girl a brother or sister. I was very careful with my diet and supplements. It took 5 months to fall pregnant but we are now a family of 4. Our little boy was born in December 2013.''

''It is possible to overcome PCOS! I’m still determined to continue the fight against PCOS and keep it under control with diet and lifestyle changes.''

http://www.pcosdietsupport.com/about-pcos-diet/

=Glossary=

'''Cyst''' - a general term for a fluid filled sac that grows abnormally on various organs (i.e. ovary, kidney cysts).

'''FSH''' - Follicle Stimulating Hormone

'''Hirsutism''' - An abnormal growth of hair on a woman's face or body.

'''hCG''' - Human Chorionic Gonadotrophin

'''GnRH''' - Gonadotrophin Releasing hormone

'''LH''' - Luteinizing Hormone

'''LOD''' - Laparoscopic Ovarian Drilling

'''PCOS''' - Polycystic Ovarian Syndrome

'''mRNA''' - Messenger Ribonucleic acid; a transcribed version of a section of DNA that is later translated to produce a protein.

'''DHEA''' - Dehydroepiandrosterone sulfate; a steroid hormone produced by various organs (reproductive organs, the brain and the adrenal glands).

=References=

<references/>