User:Z3459224

2015-10-15T12:26:21Z

Z3459224:

Talk:2015 Group Project 1

2015-10-15T12:23:04Z

Z3459224: /* Peer Reviews */

{{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.

===10===
Firstly, this is a very impressive wiki and I think you guys are setting the bar very high. The resources you have used and referenced are of really high quality and demonstrate that you have carried out extensive research and identified the information that is most relevant and important. The introductory video and all the images you have included are awesome and really help to solidify the information that you are presenting; they also add more depth to the page and provide further explanation and clarification of the information. The "Technical Progression" section is really great, well structured and provides a lot of explanation about the procedure that I found aided my understanding about major the concepts of the page.

My suggestions to improve your wiki page would be to have a second look at the layout and headings; I found they were difficult to follow and disrupted the flow of the page, for example the heading "Benefits" followed immediately by "Mitochondrial linked information" which was followed again almost immediately by "Hereditary Mitochondrial Disease". These headings made me stop and think about whether there was some information missing and I was just a little confused about whether the two latter headings came under the first. I really liked the inclusion of the legislation and ethics surrounding the topic (very interesting reading), however I am a bit concerned that they are the biggest portions of the page; I think this would be easily rectified by simple adding further explanations of the current research and journal articles that you have referred to instead of providing only one or two sentences about each. Lastly, it would be really interesting to present information about the controversial opinions/incidents surrounding the topics and also about the disadvantages of the procedures.

Over all, I think you guys have done an awesome job thus far and with a few minor changes the page will be amazing! Good Luck!

===11===

Firstly, I think your page is very well thought out and includes a lot of relevant information. The sub-headings fit in well with the topic and allow for a coherent flow of information, however it would be better if some of the sub-headings were re-arranged. For example, it might be better if the benefits section is placed after technical progression in order to really emphasize the relevance and value of this procedure. Under some sub-headings, it would be good if you could write 3 or 4 sentences summarising that section instead of having the sub-sub heading right underneath, especially for Benefits and Legal Status. This allows for a better flow of information and also makes it look more organised.

In terms of media content, I think the introductory video is great in providing a brief overview of the whole topic. I also think your choice of images for the technical progression section is great in being able to visually summarise the written information. As I could not see an original picture in your page, I think it would be a good idea to include a more visually appealling hand drawn diagram of one of your timelines. You could have the timeline going horizontally with coloured boxes coming off of it to describe the events. This can be easily hand drawn or done in word.

It's clear a lot of research has been done due to the sheer number of articles that have been referenced, especially in reference to the inclusion of several animal and human models. I like your use of timelines however I think the timeline under prohibited section is quite laden with content and can be presented in a more appealing way.

Overall, I think you guys have done a great job in setting up this page. It has the foundations to becoming a very informative and useful page.

2015-10-07T06:41:51Z

Z3459224: /* Prevention */

{{ANAT2341Project2015header}}
=Female Infertility=

[[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/>.

==Polycystic Ovarian Syndrome==
Polycystic Ovarian Syndrome (PCOS) is a common endocrine disorder, affecting up to 20% of reproductive aged women [3] It is the most common cause of anovulatory infertility [1] which refers to infertility caused by the the absence of ovulation.

=Causes=

PCOS is a disorder of heterogeneous origin with unknown aetiology <ref name=four><pubmed>21896560</pubmed></ref>. 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 <ref name=four/>. 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=four/>.

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/>.

There has been strong evidence linking the gene CYP11a 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.

====Obesity and Diet====
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. 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/>.

====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=

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.
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|500px|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 GnRH and 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 Luteinising Hormone (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]]

===The Genetics of Infertility: Current Status of the Field===
<pubmed>PMC3885174</pubmed>
This article attempted to determine the role that genetics plays in female infertility. It was noted that several prominent causes of female infertility such as Galactosemia and Primary Ovarian Failure (POF) were associated with specific genes, with the GALT gene contributing to the former condition and the FMR1 gene contributing to the latter.

===Causes of Sterility in Bosnia-Herzegovina Population===
<pubmed>PMC4499307</pubmed>
The study conducted as laid out in this article examined the causes of female sterility in the Bosnia-Herzegovina population. Married participants were arranged into various groups based upon their age. The experiment came to the conclusion that in approximately 42% of infertile married couples, female sterility was the primary cause. The two primary causes of female infertility were tubal deficiencies (31% of cases) and Diminished Ovarian Reserves (38% of cases)

===Epidemiology, diagnosis, and management of polycystic ovary syndrome===
<pubmed>PMC3872139</pubmed>
This research article examines the causes of polycystic ovary syndrome (POS), a common cause of infertility in women. The article concluded that 50-70% of women suffer from insulin resistance secondary to Type 2 Diabetes and in many cases obseity, which may contribute partially to POS. Furthermore, 85-90% of women with oligomenorrhea also had POS, suggesting that it is an underlying cause. However, the exact pathophysiology of POS was not determined.

=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> ;

* Infertility- due to anovulation caused by PCOS.
* 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>

===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 (LSH) 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.

=Treatment=
There currently is no cure for PCOS. 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.

|-bgcolor="FAF5FF"
| Lifestyle changes are highly encouraged by medical practitioners. Diet and exercise regimes can be designed with a dietitian or nutritionist.
| 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.

|-
| 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 in the ___ trial).
| 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.

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

===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.

=References=

<references/>

{{ANAT2341Project2015header}}

2015 Group Project 3

2015-10-07T06:37:02Z

Z3459224: /* Causes */

{{ANAT2341Project2015header}}
=Female Infertility=

[[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/>.

==Polycystic Ovarian Syndrome==
Polycystic Ovarian Syndrome (PCOS) is a common endocrine disorder, affecting up to 20% of reproductive aged women [3] It is the most common cause of anovulatory infertility [1] which refers to infertility caused by the the absence of ovulation.

=Causes=

PCOS is a disorder of heterogeneous origin with unknown aetiology <ref name=four><pubmed>21896560</pubmed></ref>. 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 <ref name=four/>. 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=four/>.

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/>.

There has been strong evidence linking the gene CYP11a 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.

====Obesity and Diet====
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. 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/>.

====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=

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.
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|500px|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 GnRH and 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 Luteinising Hormone (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]]

===The Genetics of Infertility: Current Status of the Field===
<pubmed>PMC3885174</pubmed>
This article attempted to determine the role that genetics plays in female infertility. It was noted that several prominent causes of female infertility such as Galactosemia and Primary Ovarian Failure (POF) were associated with specific genes, with the GALT gene contributing to the former condition and the FMR1 gene contributing to the latter.

===Causes of Sterility in Bosnia-Herzegovina Population===
<pubmed>PMC4499307</pubmed>
The study conducted as laid out in this article examined the causes of female sterility in the Bosnia-Herzegovina population. Married participants were arranged into various groups based upon their age. The experiment came to the conclusion that in approximately 42% of infertile married couples, female sterility was the primary cause. The two primary causes of female infertility were tubal deficiencies (31% of cases) and Diminished Ovarian Reserves (38% of cases)

===Epidemiology, diagnosis, and management of polycystic ovary syndrome===
<pubmed>PMC3872139</pubmed>
This research article examines the causes of polycystic ovary syndrome (POS), a common cause of infertility in women. The article concluded that 50-70% of women suffer from insulin resistance secondary to Type 2 Diabetes and in many cases obseity, which may contribute partially to POS. Furthermore, 85-90% of women with oligomenorrhea also had POS, suggesting that it is an underlying cause. However, the exact pathophysiology of POS was not determined.

=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> ;

* Infertility- due to anovulation caused by PCOS.
* 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>

===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 (LSH) 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=

==Impact of physical activity on ovarian reserve markers in normal, overweight and obese reproductive age women==
<pubmed>25509968</pubmed>
This study focuses on the effect of physical activity on fertility in three groups of women at reproductive age; normal, overweight and obese. The results from the study suggest that there was a marked improvement in fertility as shown by the ovarian reserve markers for all 3 groups, however it was most significant in the overweight and obese groups. This study is relevant to our project as it gives an insight into the preventative measures that can be taken for infertility.

==Risk factors of polycystic ovarian syndrome among Li People==

<pubmed>26276294</pubmed>
This study examined the risk factors entailed in Polycystic Ovarian Syndrdome (PCOS) amoung Li people. Using the method of a case control study, questionnaires were given to female Li people with and without PCOS. Analysis of the questionnaires showed that family history of diabetes, family history of infertility, bad mood, lack of physical exercise are all high risk factors of PCOS. As a result, management of these risk factors can be taken into consideration when preventing infertility through PCOS.

==Vitamin D and female fertility==

<pubmed>24717915</pubmed>
This article is a review focusing on research regarding Vitamin D and fertility over the past year. The review found that the levels of Vitamin D is crucial for women undergoing in-vitro fertilisation. It was also found that Vitamin D was beneficial for women with PCOS and carried a protective effect against endometriosis. These observations suggest that having sufficient Vitamin D in your body can be preventative for problems associated with fertility.

=Treatment=
There currently is no cure for PCOS. 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.

|-bgcolor="FAF5FF"
| Lifestyle changes are highly encouraged by medical practitioners. Diet and exercise regimes can be designed with a dietitian or nutritionist.
| 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.

|-
| 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 in the ___ trial).
| 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.

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

===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.

=References=

<references/>

{{ANAT2341Project2015header}}