PCOS and Fertility

Polycystic ovarian syndrome or “PCOS” is the most common endocrinopathy affecting women, with about 10% of all women in their reproductive years being sufferers.

Polycystic ovarian syndrome is just that, a syndrome, and as such can manifest with a different subset of symptoms in different women.

Some features however are relatively constant and thereby allow us to make the diagnosis. These findings include:

  • irregular menstrual cycles (attributable to disordered ovulation)
  • polycystic ovaries as seen on ultrasound, and
  • evidence of increased androgens, either clinically (as exemplified by hirsutism, acne) or in the blood testing.

Although PCOS patients tend to experience the onset of their symptoms soon after puberty, many will nonetheless choose to live with their symptoms until they reach the point when they find it difficult to conceive. As one can imagine, when ovulation is infrequent or occurring unpredictably, it will be hard to gauge the window of opportunity for appropriately timed intercourse. Moreover, even when patients with PCOS do ovulate, it is entirely possible that the ovulation may be suboptimal in terms of the hormones that precede or follow it, leading to the release of unhealthy eggs or to a deficient uterine lining (endometrium). Some data suggests that PCOS patients may have a higher miscarriage rate than other women in their age group; if so, this may relate to lining or perhaps to egg quality issues, likely arising from excessive androgens.

How should we treat PCOS patients? The first thing to realize is that PCOS patients are more than their fertility. PCOS patients are at an increased risk for cardiovascular disease despite their youthful presentation. Common risk factors found in PCOS patients are obesity (about 60%), cholesterol abnormalities, and insulin resistance (about 40%). These patients should therefore be screened with special attention to blood pressure, glucose and insulin tolerance, body weight, and serum lipids. These issues ideally should be addressed and optimized before conceiving.

PCOS patients not interested in fertility still need to address their anovulation and irregular menstrual cycles. Some patients have long bouts of amenorrhea (no periods) punctuated by heavy, often uncontrollable bleeding when their unhealthy lining begins to shed in a haphazard fashion (dysfunctional uterine bleeding or “DUB”). In the absence of regular exposure to progesterone post-ovulation, the uterine lining will usually build up slowly over time, predisposing these patients to DUB, endometrial polyps, or even endometrial cancer.

Overweight patients with PCOS will often find that losing about 10% of their body weight or more will correct much of their underlying hormonal irregularities and lead to regular cycling. Patients with insulin/glucose issues often respond to the insulin sensitization medication metformin by showing improved cyclicity. The easiest and most common solution however still remains the regular use of birth control pills. These pills expose the lining to progesterone in quantities sufficient to ensure that it stays thin and healthy. Moreover, the pills also serve to lower the amount of androgens in the patient’s system, often helping to resolve hair and skin symptoms.

PCOS patients interested in conceiving need help to ovulate, and the usual first step is a trial of the oral medication clomiphene, a type of natural estrogen antagonist that “fools the brain” into believing that estrogen levels are low. This stimulates production of the hormones FSH and LH, which then act upon the ovary to bring about egg development and ovulation.

About 70% of all women will ovulate in response to clomiphene. For those women who don’t, the usual next step is injectable FSH. PCOS patients can be difficult to stimulate with FSH though; often the responsiveness of their ovaries tends to be an “all-or-none” phenomenon with either no or way too many follicles responding to the medication. These women may ultimately require IVF in which the eggs are removed before fertilization, thereby eliminating the risk of high order multiple pregnancies. Care to avoid excessive stimulation is required as too vigorous a response can lead to the ovarian hyperstimulation syndrome in which severe bloating and dehydration occur.

Having said all this, the question still begging to be answered is “What causes PCOS?” PCOS may have more than one cause. In fact, many different pathways can lead to the same destination. It seems that too much androgen can predispose to PCOS and may trigger it rather than merely be an association. The same thing can be said for being overweight or insulin-resistant. Some PCOS patients seem to possess a primary abnormality with hormonal secretion from the hypothalamus which causes excessive pituitary LH to be produced. This in turn leads to excessive androgens. In all likelihood, the cause of PCOS is polyfactorial; i.e. there may be many different genetic precursor conditions that predispose to PCOS, and they alone or with an environmental instigator may facilitate the development of PCOS.

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