Harvard School of Public Health
Yale School of Medicine
University of California San Francisco
Division Director, REI
Stanford University Medical Center
Polycystic Ovarian Syndrome (PCOS) is a group of disorders all of which result from an interruption in a woman's endocrine (or hormone) system. From a fertility perspective, women with PCOS often ovulate an egg irregularly or not at all, making the ability to conceive without assistance difficult, and sometimes, impossible.
Unfortunately, primary care doctors, OBGYNs, and fertility doctors on a global basis do a poor job in discerning which women have PCOS. One 2010 study calculated that only 70% of women who truly have PCOS were ever diagnosed by a doctor, and over a third of women given a PCOS diagnosis did not in fact have it.
Technically, for a woman to be diagnosed with PCOS, she must meet two of three criteria.
Androgen Excess: A woman has uncommonly high amounts of hair growth on her face or back as well as acne or alopecia. The reality is “uncommonly high” can vary by race or ethnicity or can be hard to detect if the patient treats it. As a result, blood levels can be taken to detect levels of testosterone to make this diagnosis.
Ovulatory Dysfunction: If a woman gets her period more frequently than every 21 days or less frequently than every 35 days, this qualifies. However, some women can have ovulatory dysfunction and yet still have a “normal cycle”.
High Follicle Count, or Volume, Within Ovaries: A woman qualifies if she has 12 follicles growing/resting in one ovary as detected by ultrasound. Alternatively, if either ovary has a 10mL volume, this qualifies. Some doctors refer to this phenomenon as “polycystic ovaries” (hence the name Polycystic Ovarian Syndrome) but that is a misnomer: the hallmark here is a high number of follicles, not cysts.
Equally important in the diagnosis of PCOS is to rule out any issues driven by abnormal thyroid or prolactin levels as well as adrenal gland conditions.
PCOS is a highly heterogeneous diagnosis which presents itself in many different forms and phenotypes. Candidly, there is not a "one size fits all'' treatment approach, and the best path can often depend on which features (e.g. metabolic factors, low or elevated weight) are more prominent.
Generally speaking, weight loss helps PCOS patients who have a high body mass index (BMI) to restore normal ovulatory function (if that is an underlying issue) and ultimately, conceive. We should note, some women of LatinX heritage who have PCOS have lean PCOS and for women with lean PCOS, much of the diet and exercise data we'll describe doesn't apply.
Strategies for weight loss often incorporate both diet modification (calorie restriction) and exercise (increased physical activity). Even under intensive weight restriction programs, less than one-third of PCOS patients with a high BMI lose 10% of their body weight. Yet, the data shows that pursuing a weight loss strategy can be effective for PCOS patients with a high BMI who are trying to conceive.
Let’s look at one study conducted in the United States on mostly Caucasian women who have PCOS and a high body mass index. The data showed women who took oral medication like Clomid managed to improve their odds of success when they incorporated dietary improvements and exercise.
Having established that diet and exercise help for women who have PCOS, are anovulatory, and have an elevated BMI, the next key question is whether it’s so helpful that it warrants delaying fertility treatment to try and lose weight.
Amongst younger women with a high BMI with no other indication of infertility (e.g. poor egg quality or sperm), the answer appears to be yes. In comparing two U.S. National Institutes of Health studies, amongst women who underwent 16 weeks of diet and exercise before advancing to oral medication for ovulation induction, success rates were far higher than amongst similar women who skipped diet and exercise and proceeded directly to oral medication.
However, this may not be true for women with a condition where IVF is likely necessary (e.g. women with poor egg quality, who are relying upon poor quality sperm, or have a tubal blockage—which we covered earlier). Time is especially of the essence for these women if they are older, since IVF success rates on a per-cycle basis quickly diminish after age 35. For many of these patients, it’s not worth the trade-off of lost months (or years) to see if they can reduce their body weight.
Most PCOS patients trying to conceive will suffer from ovulatory dysfunction. If a woman is not able to ovulate an egg she won’t be able to conceive naturally.
For these patients, a first line of medical treatment is to take ovulation induction drugs like Clomid (clomiphene) or Femara (letrozole) and to time intercourse to coincide with ovulation. Ovulation induction drugs are easy to take (oral) and relatively inexpensive versus other fertility treatment drugs.
Generally speaking, the research suggests letrozole (Femara) is the superior choice as shown by the data below in PCOS patients with fertility challenges. According to this New England Journal of Medicine study an especially large difference was recorded amongst women with a higher body mass index.
IUI with ovulation induction (e.g. letrozole or Clomid) is no more effective than ovulation induction on its own. For that reason, unless the PCOS patient also is using poor quality sperm (see our lesson on the semen analysis here), there is not much added benefit to adding an IUI to a letrozole or Clomid cycle.
Alternatively, IUI success rates when accompanied by gonadotropin (a more potent, expensive, injectable hormone) are dramatically higher than ovulation induction alone or ovulation induction with IUI. You will recall in the previous studies, four cycles of letrozole achieved roughly 20%–30% cumulative success rates. As you can see below, a single IUI with gonadotropin produces similar results.
However, a third of these pregnancies involved twins or triplets which, for many, is an unacceptably high level of risk to take on. As a result, many doctors steer patients away from this route. If a PCOS patient does pursue IUI with gonadotropins, she must be monitored closely and be prepared for her doctor to start and cancel multiple cycles in trying to find a gonadotropin dose that is likely to be safe and effective. It's critical patients talk with their doctor about the risk of accompanying an IUI with gonadotropins, but the issue is especially pressing if a woman may have PCOS.
Women with PCOS have seemingly comparable, or higher rates, of success with IVF as most other patients. Below you can see the live birth rates after one IVF cycle for U.S. patients with ovulatory dysfunction (many are likely to have PCOS) and those of similar ages with a uterine factor or diminished ovarian reserve.
When investigators looked at IVF success data amongst PCOS patients, they noted no significant difference between patients put on the "long agonist" drug protocol or the "antagonist" protocol. A broader meta analysis of 10 studies revealed a similar finding but that PCOS patients suffered lower rates of hyperstimulation on the antagonist protocol because it features a Lupron-only trigger.
Amongst PCOS patients treated in China, investigators noted in the New England Journal of Medicine higher rates of success from "frozen" transfers rather than "fresh" transfers. In this case, patients also suffered lower rates of hyperstimulation.