How to Treat PCOS Infertility and Ovulation
Infertility and difficulty getting pregnant can be one of the primary concerns for sufferers of PCOS, however the good news is that it is incredibly rare for women with PCOS to be infertile. There are a wide range of tools available for women with PCOS to induce a regular ovulatory cycle and get pregnant, from lifestyle changes to medicines or surgeries. In this article we will cover all of the most commonly used techniques and strategies for inducing ovulation, explaining how they work and when they should be used.
Before you read about treatments, make sure you have read our article Ovulation, Menstruation and PCOS: What Goes Wrong? to be sure that you understand how these treatments are working.
Contents
The typical order of therapies used to induce ovulation and conception in women with PCOS.
Lifestyle Management: Weight loss and more
As we know, obesity and PCOS are strongly linked with around 50% of all women with PCOS also being obese [source]. Obese sufferers of PCOS are more likely to suffer from anovulation (where the ovary does not release an egg) compared to lean sufferers of PCOS [source]. The reason for this is that obesity increases insulin resistance, which leads to excess insulin production (hyperinsulinemia), which causes excess testosterone production which finally prevents proper follicle maturation (anovulation) [source].
“A 5% drop in weight restores ovulation for most women”
It has been repeatedly demonstrated in large and well designed studies that for obese women with PCOS, sustainable weight loss via long-term diet and exercise is effective in restoring normal ovulation cycles, resulting in pregnancy. A 5-10% drop in body weight is sufficient to restore normal ovulation cycles for most women [source]. Additionally, overweight women are less likely to respond to other methods of ovulation induction so to increase the chances of getting pregnant sustainable weight loss to a BMI of less than 30 should be a goal for all PCOS sufferers [source]. This has additional benefits of helping to prevent Type 2 diabetes and Cardiovascular disease [source].
It is highly recommended that gradual weight loss is preferable to sudden weight changes, as research shows that people that undergo gradual weight loss are far more likely to maintain their new body weight, whereas sudden weight loss subjects are more likely to relapse and regain weight.
No single diet has been proven to be best for PCOS weight loss. The one common factor in all successful weight loss diets for PCOS has been a calorie deficit, in other words, consuming less energy than you are spending each day. A simple method for this is to calculate your basal metabolic rate (BMR) using a calculator like this, then using a nutrition tracking app, like this, to monitor your daily food intake and aim for a few hundred calories lower than your BMR. Studies have compared dietary compositions such as high carb vs high protein and found that neither is superior as long as a caloric deficit is maintained [source].
In addition to weight loss, routine moderate exercise is highly effective at improving insulin sensitivity, even if not weight loss is achieved or required [source]. Exercise can range from walking, swimming, jogging, weight lifting, or playing sports like tennis or football. Excess caffeine intake, alcohol intake and smoking are also all risk factors that should be avoided in order to increase the likelihood of successful ovulation [source].
Lastly, a body of evidence is beginning to emerge that dietary supplements such as sage, cinnamon, or inositol can be effective in helping to restore normal ovulation cycles however further work in this area is certainly required before it can be recommended as an outright treatment [source]. Given their dietary nature, there is no harm in incorporating some of these foods or supplements into your usual diet as they are typically low cost and without side effects at the recommended doses.
Clomiphene Citrate
Clomiphene Citrate, also referred to as Clomiphene, has been used to induce ovulation in PCOS sufferers for the past 50 years [source]. Clomiphene works by blocking the effects of estrogen in parts of your brain (the hypothalamus and pituitary) which stimulates your body to produce more Follicle Stimulating Hormone (FSH). Increasing levels of FSH are highly effective at inducing ovulation.
For more information on why FSH stimulates ovulation: Ovulation, Menstruation and PCOS: What Goes Wrong?
Women with PCOS may have many paused, under developed follicles which can all be sensitive to FSH. Therefore, women with PCOS may have an overresponse to Clomiphene resulting in multiple follicles ovulating which can lead to multiple pregnancy. Interestingly, women that do not have PCOS tend to be very unresponsive to Clomiphene, despite the fact that they use much higher doses.
“80% of women with PCOS will ovulate using Clomiphene”
Clomiphene treatment will typically start around 50mg per day for 5 days, beginning between days 2-5 of the menstrual cycle [source]. Menstruation can first be induced using progestin in order to reset the cycle if it is particularly irregular. After administration of Clomiphene, the subject will see a doctor regularly to monitor follicle development. If multiple follicles are developing then the dose can be reduced to 25mg per day. On the other hand, the dose can be increased to as much as 250mg per day if required, but only under very controlled conditions and for a short period of time as the recommended dose is only 100mg per day [source]. The doctor will monitor for ovulation using techniques such as body temperature pattern monitoring, blood progesterone levels or even urine sample to check for surges in levels of Leutinising Hormone [source].
70-80% of all PCOS sufferers will ovulate on clomiphene, with at pregnancy rate over 6 months of approximately 67% [source]. It is thought that the reason that some women cannot conceive using Clomiphene, despite ovulating successfully, is because Clomiphene also sends a signal to the endometrium (the lining of the uterus) to stop growing, which can make implantation of the fertilised egg difficult. The doctor can monitor endometrium thickness using ultrasound and recommend other treatments if it is consistently too thin [source]. If pregnancy does not occur within 6 successful cycles then the doctor will typically recommend a different treatment.
Clomiphene is associated with some side effects such as hot flushes, bloating, mood swings, breast tenderness, nausea, dizziness, and blurred vision. Additionally, the chance of having twins or triplets is slightly higher. Despite the side effect, Clomiphene is considered the first line of treatment for non-obese PCOS sufferers having difficulties conceiving due to its high success rate and safety. Regular ultrasound scans will help to monitor any risks of multiple pregnancy as well as being able to advise on optimal intercourse timing.
Insulin Sensitisers
Insulin sensitisers can be used to counteract the effects of excess insulin that are common with PCOS. Not all insulin sensitisers can be used for this as not all of them are considered safe. The most commonly used and the most well research treatment is Metformin. Metformin works by preventing your liver from making glucose and stimulating the rest of your body to absorb glucose, reducing the need for your body to produce insulin [source]. Many studies have been carried out to research the effectiveness of Metformin for inducing ovulation and pregnancy. Results show that Metformin is useful for inducing ovulation however it is far more effective when used in combination with Clomiphene. In general, Clomiphene is regarded as a better treatment however some women may be resistant to Clomiphene or may have intolerable side effects to it. In that case, Metformin is an effective substitute [source]. Additionally, Metformin and Clomiphene combination therapy may also be more effective for PCOS sufferers who are older and have higher levels of visceral obesity (fat around the abdominal area and organs) [source].
Metformin has some side effects that may be quite unpleasant for some people, such as nausea, bloating, cramps, or diarrhoea. For that reason, treatments should start at around 250mg daily and slowly increase as tolerance grows to the optimum level of around 500-750mg 3 times per day with food.
Some small studies have shown that continuing metformin use throughout pregnancy can reduce the risk of complications such as spontaneous abortion however these studies were not randomized controlled trials so much more research should be done before this can be recommended [source].
Intramuscular Gonadotropins
Intramuscular Gonadotropins are injection that contain high levels of Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH). These injections can be used if the above treatments were unsuccessful or unavailable. Raised FSH and LH levels cause follicles to grow and mature. Regular blood and ultrasound monitoring will be used to determine when a follicle has reached the correct size, at which point Human Chorionic Gonadotropin is administered to induce ovulation. The successful pregnancy rate using this method is around 25% per cycle [source]
Although they are quite effective at inducing ovulation and pregnancy, Intramuscular Gonadotropins carry a much higher risk of multiple follicle development and multiple pregnancies, despite careful dosing. For this reason, treatment is cancelled if 3 or more follicles are detected growing [source]. Additionally, the injections can be quite expensive, and the check-ups and monitoring required for safety can be quite intensive. Despite this, Intramuscular Gonadotropins are still a good strategy for inducing ovulation if the previous treatments are unsuccessful.
Laparoscopic Ovarian Drilling
“80% of women with PCOS will ovulate using Ovarian Drilling”
Laparoscopic Ovarian Drilling (LOD) is a minimally invasive, non-destructive surgery. It is performed using a laser or cautery to create small perforations in each ovary [source]. The surgery induces normal ovulation for a period of time however this change is not permanent. It is not well understood how exactly LOD induces this correction, but it is thought to be related to the thermal damage caused to the ovary. Approximately 80% of PCOS sufferers will ovulate using LOD with a pregnancy success rate very similar to that of Intramuscular Gonadotropins, so is considered an alternate strategy.
Like Gonadotropins, LOD should be considered as a backup for PCOS sufferers that do not respond to Clomiphene or Metformin. LOD also has a significantly reduced chance of inducing multiple pregnancies compared to other methods discussed here. Despite the benefits, there are some concerns around post-surgery adhesion formation (when the ovaries stick to other surfaces in the body after surgery) however the rates are extremely low [source].
Aromatase Inhibitors
Aromatase inhibitors, such as Letrozole or Anastrozole, are treatments typically used for breast cancer however they are also effective at inducing ovulation in women with PCOS. Aromatase Inhibitors work by blocking the conversion of testosterone to estrogens, like estradiol. In a similar manner to Clomiphene, the reduced action of estrogen in the brain leads to a higher production of gonadotropins like FSH and LH, resulting in follicle growth and ovulation. Additionally, Aromatase inhibitors appear to have less negative effects on growth of the endometrium, leading to more successful implantation after conception, however the results of research in this area is not completely conclusive and more work needs to be done to confirm this.
In 2005, a warning was issued by the manufacturers of Letrozole after studies in rats shows that it may have toxic effects for the embryo and foetus as well as teratogenic (deformation) effects resulting in higher rates of cardiac and bone abnormalities in newborns [source]. However, a later study of around 900 infants appears to have disproved this theory, although Aromatase Inhibitors are now rarely prescribed to induce ovulation [source].
In Vitro Fertilisation
In Vitro Fertilisation, or IVF, is the final line of defence for women with PCOS who have not responded, or cannot use, any of the other options mentioned above. In IVF treatment, gonadotropins like FSH are used to achieve the development of multiple follicles. The eggs are then safely retrieved, and embryos are developed before being transferred back into the uterus. Multiple embryos are normally transferred to the uterus as they are not all successful. Pregnancy rates with IVF is around 50% however success decreases with age [source]. Side effects can include multiple pregnancies, but this is much more easily controlled compared to other treatments. Additionally, excess embryos can by cryogenically frozen and preserved so that they can be used later, if desired.
Final Thoughts
As with all aspects of PCOS, whether you’re talking about symptoms, causes or treatments, it’s essential to remember that is a complex disease. It has no one single cause, but rather is caused by a combination of many different factors such as genetics and lifestyle. This is why PCOS is so varied from person to person. Each case has to be evaluated and treated on an individual basis, there is no one-size-fits-all treatment. A treatment that works on your friend may have no effect on you. Similarly, there is no magic bullet cure for PCOS, instead we have to address each cause and symptoms to manage the disease and live the life you want.
For many people, the thought of not being to conceive children because of PCOS is one of the first, and scariest, reactions upon being diagnosed. It can be the source of considerable stress and anxiety, and be the route of serious mental health problems. If there is one thing to take away from this article, we urge you to remember that it is incredibly rare for somebody to be completely infertile due to PCOS. There is a treatment for just about everybody, and often it’s as simple as counting calories or taking some pills for a few months. It may require a bit more planning and a bit more patience, but you will get there eventually. To make the whole process more manageable, take the time to find a good doctor, gynaecologist or endocrinologist that can assess and guide you. Monitor mental health regularly and seek advice and treatment for it just as you would your physical health.
PCOS Centre wishes you all the luck in the world for your family raising endeavours, and when you find success we would love for you to let us know.
