How PCOS affects fertility
There are three pathways that PCOS can impact your ability to become pregnant: anovulation, Insulin Resistance, and elevated androgen (male hormone) levels.
Anovulation means that even though your ovaries still have eggs in them, the hormonal balance does not allow them to mature as needed to ovulate, which is the reason PCOS is the most common cause of anovulation.
Insulin resistance has been established as a significant part of all three pathways involved in how PCOS affects reproductive hormones. Insulin resistance is now recognized as a defining characteristic of PCOS and a major factor in the development of PCOS, as well as a contributor to infertility from anovulation and miscarriage, as well as to the development of reproductive problems, including anovulatory infertility. An increase in androgens due to elevated levels of insulin in the current body of research is directly correlated with interfering with the development and release of eggs and the potential for small cysts on the ovaries, further hindering fertilization and causing additional complications during pregnancy.
Thirdly, the quality of eggs affects fertility as well. Eggs released from the ovaries of women who have PCOS and/or are insulin resistant have lower maturity, fertilization, and embryo development compared to women who do not have these conditions, and therefore, even when ovulation occurs, they may be at an increased risk for failure to conceive.
It is very promising that insulin resistance is highly responsive to treatment. Even losing a small amount of weight may significantly improve fertility for women with PCOS.
Can you get pregnant naturally with PCOS?
It is important to state clearly that there is some confusion and misinformation about PCOS and that it can sometimes be difficult for a woman with PCOS to conceive her own child. While having PCOS may impact the time it takes to conceive, it does not mean a woman with PCOS cannot get pregnant. Evidence shows that more than 60% of women with PCOS can spontaneously ovulate within months if they improve their lifestyle changes and lose weight. Once a woman starts to ovulate, her chance of conceiving is about the same as that of other women. Therefore, if a woman can lose just 5-10% of her total body weight (if she is overweight), there will be a significant improvement in her ability to get regular periods and to ovulate. This is a realistic goal that is attainable, not something that requires a lot of effort and change.
If you have PCOS, tracking your fertile window is even more critical because your cycles are not as regular; your cycles may vary in length and in terms of ovulation timing. There are many ways you can utilize cycle tracking to determine when you may be fertile, even when cycles are not consistent, such as using a basal body temperature chart, ovulation predictor kits, and monitoring your cervical mucus. However, since ovulation occurs later on in the cycle of a woman with PCOS, using two or three tracking methods will give you a better picture of your chances of becoming pregnant than using only one method.
Your chances of getting pregnant naturally are the highest when you have been having your periods consistently, regardless of how much variation there has been in their lengths, and when you have properly managed your overall metabolic health. You can manage your metabolic health by maintaining balanced nutrition, exercising regularly, and managing your stress and sleep according to what works best for you.
If you have made a consistent effort for six months to a year to become pregnant but have not yet succeeded, you should contact a medical professional to help with your efforts instead of making further attempts to get pregnant on your own.
Medical treatments to help you ovulate
If lifestyle changes are not restoring your ovulation, several available well-studied medications may help. The most recent data clearly show one of these medications to be the preferred treatment.
Letrozole continues to be supported as the preferred first-line medication for initiating ovulation. Letrozole is more effective than clomiphene citrate in inducing ovulation and live birth rates. A large meta-analysis that included over 4,200 women found that letrozole increased pregnancy rates when compared with clomiphene by more than 57% (the statistical significance of this finding has resulted in many fertility guidelines now recommending letrozole as the first choice).
Clomiphene citrate (Clomid) continues to be an established alternative and is still prescribed frequently. Approximately 80% of women with PCOS who are treated with clomiphene citrate will successfully ovulate; approximately 50% of those women will conceive without assistance within six cycles.
Metformin functions in an alternative way to induce ovulation; its mechanism is to enhance the body’s reaction to insulin, thereby assisting with the establishment of normal ovulatory cycles over a period of time. Metformin can be especially beneficial to insulin-resistant women, and it is frequently prescribed in conjunction with other therapies rather than by itself.
Inositol is a naturally occurring substance that has been used to improve ovulation via insulin sensitivity, and it is sometimes used together with or before the use of pharmaceuticals.
Your doctor will assess your hormone level, body weight, and response to date and recommend the best starting point for treatment.
When to Move to IUI or IVF
Women who have not conceived after multiple rounds of ovulation induction (either with letrozole or clomiphene) often move to more invasive forms of assistance (either intrauterine insemination (IUI) or in vitro fertilization (IVF)). Timing is dependent upon specific criteria. Most providers suggest three cycles of IUI for women suffering from Polycystic Ovary Syndrome (PCOS) before beginning IVF, because research indicates that most successful IUI pregnancies occur within the first three cycles for women with PCOS.
The IUI process involves the insemination of prepared sperm (previously washed) directly into the uterus during ovulation; this makes it less invasive than IVF and also less costly than IVF; therefore, the use of IUI as a middle approach between just using ovulation induction and beginning IVF is reasonable if there has been no success with ovulation induction treatment alone.
Age greatly influences how quickly to start the process of escalating treatment. In patients under 35 years old, three to four inductions + 3 cycles of IUI is an acceptable pathway. For ages 35-37 years old, most doctors feel that 2-3 unsuccessful IUI’s should prompt an immediate transition to IVF. Once a patient reaches 38 years old, many doctors suggest proceeding to IVF with no or 1-2 total cycles of IUI since age is a much larger issue and IVF has significantly higher per-cycle success rates than IUI does.
There are additional factors that would affect an earlier transition to IVF, such as blocked tubes, a significant male factor (ie the man has low counts or poor sperm quality), low ovarian reserve, and a history of multiple failed cycles with no clear explanation as to why. The decision is always individualized and based on your overall medical picture and age, with your doctor making recommendations based on your complete health status.
IVF with PCOS — What’s Different?
Women with Polycystic Ovarian Syndrome (PCOS) can benefit significantly from In Vitro Fertilization (IVF). Still, the approach to IVF for women with PCOS needs to be tailored differently from that for women without PCOS. Understanding the differences in protocol will help you prepare for treatment and make informed decisions before starting IVF.
The main difference in the IVF protocol is how stimulation is done. Women with PCOS typically respond to stimulation medications more easily due to their elevated Antral Follicle Count and elevated Anti-Müllerian Hormone level (AMH). The 2024 ASRM guidelines recommend that women with PCOS, elevated AMH, and expected high egg yield be informed of their increased risk of developing Ovarian Hyperstimulation Syndrome (OHSS) before IVF treatment and have measures in place to reduce the possibility of developing OHSS.
The preferred method of stimulating ovaries in PCOS patients is the GnRH antagonist protocol because it has less risk of OHSS than the older protocol with GnRH agonists. In addition, your doctor will typically begin stimulation with a lower dose of FSH and monitor you closely throughout the cycle. Triggering final egg maturation with either a GnRH agonist (instead of hCG) and using a freeze-all approach (whereby all embryos are frozen and not transferred fresh) is the best combination to prevent OHSS in this group of patients.
Women with PCOS who are undergoing IVF will produce more eggs per cycle, resulting in a better starting number of embryos. The chances of delivering a live baby are comparable between women with and without PCOS. They may, in fact, be higher for PCOS women once the use of frozen embryos is included in the final analysis.
Lifestyle Changes That Actually Help
The first-line treatment for all women with PCOS is lifestyle change, irrespective of their weight, and evidence supporting its effect on fertility is convincing.
If weight is an issue, your best option to improve your chances of getting pregnant may be to lose weight. Simply losing 5% of your total body weight will improve the ability to ovulate and regulate menstruation for women with PCOS. If you lose weight, you also improve your insulin sensitivity, decrease your androgen level(s), and shorten the amount of time it takes for you to become pregnant.
The quality of diet is more important than any specific dieting method. The guideline said “there is no true best diet” for women with PCOS; rather, women with PCOS need to avoid processed foods, decrease refined carbohydrates and sugar, and choose foods that help maintain stable blood sugar levels. Foods that are low in the glycemic index, high in fibre, and contain omega-3 have all been shown to help create the types of environments with insulin that allow for successful ovulation.
Exercise is an independent factor of female fertility, and the guidelines recommend 150 minutes of moderate activity or 75 minutes of vigorous activity weekly. Studies have shown that vigorous cardiovascular exercise has beneficial effects on insulin resistance, body composition, and aerobic fitness of women with PCOS, even if there was no significant change in the women’s weight.
Among many possible supplements to improve PCOS symptoms, inositol is the most well-supported in research as it relates to ovulation and insulin sensitivity. Still, vitamin D and omega-3s should be considered as well if a woman is deficient in these vitamins. Be sure to speak with your physician about any supplements you take before starting them.
Frequently Asked Questions
References:
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Anna Haotanto is the Founder of Zora Health and a passionate advocate for women’s empowerment. Anna’s personal experiences with egg-freezing, PCOS, perimenopause and the challenges of fertility have fueled her mission to provide high-quality information, financing, and support to help women and couples navigate their fertility journeys with confidence. She is also recognised for her achievements in finance, entrepreneurship, and women’s empowerment, and has been featured in various media outlets. You can also follow her on Linkedin or Instagram.
