We recently asked the Instagram TTC community what they wanted to hear more about and the resounding response was PCOS (Polycystic Ovary Syndrome). For those who may not be aware, Polycystic Ovary Syndrome (PCOS) is a health problem which affects approximately 1 in 10 women. That’s huge! With so many of you wanting to know more about how it can be treated and how it can affect fertility, we’ve spoken to the brilliant Fertility Specialist, Dr Despina Mavridou at The Women’s Wellness Centre in London, to find out all about it and the latest development in the treatment of Polycystic Ovarian Syndrome (PCOS). She also talks about when to seek fertility advice and help.
The Women’s Wellness Centre in London have the most resourceful and supportive free Facebook group, which we would strongly recommend you join.
Over to Fertility Specialist, Dr Despina Mavridou…
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The important part of PCOS, as the name suggests, is that it’s a syndrome. A syndrome is a group of symptoms consistently happening together. PCOS does not involve just one single body part (or a specific defect that causes a dysfunction within a body part), it is a set of pathological manifestations that occur in multiple systems in the body.
PCOS is characterised by either irregular periods or infrequent periods, androgenic symptoms (increased levels of androgen) and ovaries looking polycystic (multiple cysts) on an ultrasound scan. PCOS is also associated with increased insulin resistance and diabetes, endometrial hyperplasia and endometrial cancer and cardiovascular disease.
What Are The Symptoms of PCOS?
Due to the multiple symptoms that women with PCOS experience (and due to the multiple body systems involved and many hormonal pathways disturbed), it can be difficult to explain to patients/women during consultations what PCOS is. If you feel you have symptoms, it may be worth seeking fertility help with a fertility specialist if you’re trying to conceive or thinking about TTC.
Diagnosis of PCOS
Using agreed diagnostic criteria, 2 out of the following 3 would be needed in order to diagnose PCOS:
Irregular periods (or no periods)
Elevated levels of androgens (acne or hirsutism)
Polycystic looking ovaries on ultrasound scan
Many women will not fit this picture completely and will be undiagnosed or misdiagnosed for years. So, if you have any of the symptoms mentioned above, please ask your doctor to evaluate you for PCOS.
It is important to have the diagnosis early on in reproductive years, not just when trying to conceive, as PCOS has other long-term health implications apart from sub-fertility, such as diabetes, cardiovascular disease and cancer. We talk later on about how PCOS may need fertility treatment with a fertility specialist if you’re trying to conceive.
What is Androgen Excess?
Essentially, androgen hormones that are normally found high in males are high in women with PCOS. The androgen levels in women with PCOS are usually lower than the ones in males, but higher than the levels in women without PCOS. Typical things you look for in PCOS of androgen excess are signs of Hirsutism and Acne. Hirsutism is excessive hair that is not usually found, for example on your face, upper lip, abdomen and back.
How Common is PCOS?
In reproductive age women, PCOS is found to be the most common endocrine condition (system of glands that make hormones). It is estimated that 5-10% of all women have PCOS, the most common cause of infertility in women who have ovulatory problems. PCOS is more common in obese women, with up to 80% of PCOS patients being overweight. In general, there are four common causes of sub-fertility: male factor, unexplained, anatomical and tubal factors, and ovulatory problems.
Read here about male infertility and Mico-TESE sperm retrieval
Is PCOS Hereditary?
Even though there are many factors which have a bearing on PCOS, there is a genetic component to the aetiology (set of causes). PCOS is strongly associated with Type 2 Diabetes, which is hereditary – we know this because In populations that have a higher prevalence of Type 2 diabetes, there is also higher prevalence of PCOS.
Usually, PCOS is more comment South East Asian populations.
What Causes PCOS?
Unfortunately it’s complicated, with no definitive proof of what causes PCOS. Fortunately, however, there is ongoing research on this topic. There are many theories, but not one clear cause.
There are intraovarian increased androgen concentrations in women with PCOS; there are high numbers of follicles in the ovaries compared to women with no PCOS at the same age. This is because there is no ovulation happening, and follicles, in a way, don’t want to come out.
The two-cell theory considers how oestrogen and androgen are produced in the ovary. In PCOS, LH (Luteinizing hormone) concentration is much higher, with more androgen concentration in the ovaries. There is also Insulin resistance in PCOS which also affects androgen concentration.
Ultrasound Findings of PCOS
Normally, at a scan there is a follicle seen in the ovaries which is the dominant one or the ‘chosen one’ and this will continue to grow and release the egg. We then have the corpus luteum left behind after ovulation. The number of follicles seen on the scan is a representation of ovarian reserve and this is assessed by a fertility specialist. There is a group of women who have ovaries that look like they have many follicles or PCOS without actually having the syndrome. This is usually found in women in their 20s who have a high ovarian reserve but not necessarily PCOS. The level of Anti-Mullerian Hormone produced by the follicles is a reflection of ovarian reserve. This is also best interpreted by a fertyility specialist. Some women have high AMH, indicating a high ovarian reserve or possibly PCOS. Thus AMH has been suggested as an additional criterion for diagnosing PCOS but is not yet officially used. Also, other endocrine disorders need to be excluded, such as thyroid disease and hyperprolactinaemia (a raised level of prolactin in the blood).
Related article: ‘Are my Eggs Diminishing in Number, as I Approach 35?’
Is PCOS Related to Oestrogen Insufficiency or Premature Menopause?
PCOS and early menopause are two distinct conditions that share some similar symptoms. As women with PCOS have a higher than average ovarian reserve, they reach menopause at an older age than women with no PCOS. On ultrasound scans, in terms of number of follicles, women with PCOS aged nearly 40 have ovaries that look like the ovaries of 30-year olds . Again, this needs to be carefully assessed before final diagnosis.
How Does PCOS Impact Fertility?
PCOS inhibits regular ovulation – if no egg is released, there is no fertilisation or implantation. In a 20-year-old with PCOS where she ovulates 3-4 times per year, with regular sexual intercourse it might be enough to fall pregnant because the fecundity per ovulation ratio is high. This might not be the case in women in their late thirties. It is worth having this assessed with a fertility specialist over a period of time.
Read an article here on ovulation tracking when TTC
Women can influence the frequency of ovulation through lifestyle changes. For example, a woman with PCOS and a BMI of 40 who makes nutritional and exercise changes to her lifestyle, may be able to regain regular periods and ovulation, reversing the diagnosis of PCOS. This is not absolute and it depends on the severity of PCOS.
Is it Essential to Know if You Have PCOS Early On?
For many reasons, women have more choices if PCOS is detected early on in their reproductive years: in discussion with their doctor, they can plan not only their fertility and building their family, but also the long-term management of PCOS. General health promotion and screening by a clinician is especially important for PCOS women, who have an increased risk of metabolic syndrome, diabetes and cardiovascular disease. It is essential these are managed in a multidisciplinary approach with the correct nutrition, exercise and general health.
Read an article here on how to optimise egg quality through nutrition
Our aim as clinicians is not only to help women fall pregnant, but also to ensure they have a healthy pregnancy and, by reducing the risk of diabetes and cardiovascular disease, to enable them to grow old and enjoy life with their children
Do Women with PCOS have Higher Risk of Certain Cancer?
In women with PCOS, there is a drawn-out follicular phase, with a prolonged build up of oestrogen and prolonged thickened endometrium. There is no progesterone secretion as the follicle does not release the egg, nor is there the corpus luteum (mass of cells that forms in an ovary), which normally produces progesterone. Without progesterone, the oestrogen secretion from the follicles is unopposed, which causes a thickened endometrium and this can lead to endometrial cancer.
What Kind of Test can Women Ask for to Check for Endometrial Cancer or Endometrial Hyperplasia?
If there is a high suspicion of endometrial hyperplasia or cancer, an endometrial biopsy can be done at the clinic. This is a decision that a clinician needs to make based on ultrasound findings and an individual’s medical history. Endometrial hyperplasia is the preliminary stage of cancer and, if found, is easily treated with high doses of progesterone. There are ways of protecting the endometrium.
Weight and PCOS
Is weight the cause or a symptom?
Obesity is not the cause of PCOS, but is an exacerbating factor which can sometimes be removed by lifestyle changes. Ask your doctor for the right advice. Not every overweight woman will have PCOS.
Is it harder for women with PCOS to lose weight, compared to women with no PCOS? Is there medical evidence of this?
Losing weight is hard for anyone who is obese. This is a national problem that governments find challenging to tackle. In PCOS women, the hormonal and metabolic situation makes it even harder. We always encourage women to try and lose weight by tracking their meals and implementing nutritional advice on types of carbohydrates and reducing processed foods, as well as foods with a high sugar content.
Read an article here about how, when and why exercise is beneficial for conception.
Medical treatment for weight loss in PCOS
The main medication which has been discussed over the years is metformin. PCOS is the most commonly misdiagnosed condition and metformin the most mis-prescribed medication. In the early 2000’s, metformin emerged as one of the treatment options for Type 2 Diabetes, as it was found to reduce sugar levels. It was also found it could help with ovulation in PCOS, as there is a known overlap of PCOS and Type 2 DM (Diabetes Mellitus). There was a lot of excitement and enthusiasm at the time but, after extensive research, it has been suggested that diet and lifestyle changes have better results than metformin. In respect of ovulation induction treatment, it was also found that clomid was superior to metformin.
Treatment of PCOS for Fertility
The main medical approach to induce ovulation is with clomid (clomiphene) which is an oral medication. It induces ovulation in women who do not ovulate and induces more than one follicle in women who already ovulate.
Another medication is letrozole, which is an aromatase inhibitor which assists in the conversion of androgen to oestrogen (used in breast cancer patients to reduce oestrogen levels in oestrogen sensitive tumours). The question is whether letrozole is better or worse than clomiphene, which is the traditional treatment used for a number of years. Studies showed that letrozole was better than clomid in terms of live births and also has fewer side effects than clomid and fewer twin births. A possible link between Letrozole and birth defect risk has caused controversy but studies have found the concern to be unwarranted. If letrozole does not work, then injectable gonadotropins would be the next step of treatment. Your fertility specialist will advise you alternative options, usually IVF.
How effective are GnRH analogue injectables?
FSH analogues are very effective but there is the risk of producing multiple follicles. Injectable GnRH analogues are used as part of timed intercourse or IUI set up. This form of treatment can result in higher risk of multiples and these patients need to be monitored closely as there is a narrow window in which the treatment works and also because in PCOS patients there can be a sudden increase in follicle formation once the threshold is reached. This close monitoring is done by ultrasound.
Sometimes, it is not possible to induce the follicle safely and, in this case, the treatment plan is converted into IVF where the follicles can be collected all at once.
Playback our #fertilityexpertslive with Dr Mavridou about fertility tests and what can be learnt from a failed cycle here.
Does PCOS affect the foetus in utero?
A study published in 2018 investigated the role of high AMH levels in pregnant PCOS mice on the development of the foetus, and whether this contributed to the pathogenesis of developing PCOS in adulthood. They found that mice offspring had developed PCOS-like reproductive and endocrine phenotype in adulthood. They then treated GnRH antagonists to block these effects, which restored the adult offspring to a normal state. This could also be a potential new therapeutic avenue.
Click here to book a consult with Dr Mavridou today.
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