The most common cause of oligo-ovulation and anovulation—both in the general population and among women presenting with infertility—is polycystic ovarian syndrome (PCOS) (139). The diagnosis of PCOS is determined by exclusion of other medical conditions such as pregnancy, hypothalamic–pituitary disorders, or other causes of hyperandrogenism (e.g., androgen-secreting tumors or nonclassical congenital adrenal hyperplasia) and the presence of two of the following conditions (140):
Oligo-ovulation or anovulation (manifested as oligomenorrhea or amenorrhea)
Hyperandrogenemia (elevated levels of circulating androgens) or hyperandrogenism (clinical manifestations of androgen excess)
Documentation of elevated serum LH:FSH ratios and hyperinsulinemia are not required for either diagnosis or treatment of PCOS (139,140). Patients with PCOS should be counseled and screened regarding potential metabolic disease and obstetric complications prior to fertility treatment (141).
Ovulation Induction in Women with Polycystic Ovarian Syndrome
Despite the use of similar medications, the indications and goals of ovulation induction should be distinguished from those of superovulation. The goal of ovulation induction refers to the therapeutic restoration of the release of one egg per cycle in a woman who either has not been ovulating regularly or has not been ovulating at all. In contrast, the explicit goal of superovulation is to cause more than one egg to be ovulated, thereby increasing the probability of conception in women with unexplained infertility (136).
Weight Loss Obesity in PCOS patients is associated with poor infertility treatment outcomes (139,142–144), although the impact on pregnancy loss rates is less clear (141,142,145). Given that even a 5% weight loss may improve pregnancy rates, weight loss should be encouraged in all overweight and obese infertility patients (139). Generally, lifestyle modification is the first-line therapy, followed by pharmacologic treatment and weight-loss surgery (139). Lifestyle recommendations include a decrease in daily caloric consumption by 500 kcal and regular physical exercise, although the optimal regimen for the latter is unknown (139,146). Weight loss interventions should be undertaken prior to attempting conception in patients with excess body weight (139).
Clomiphene Citrate (Clomid, Serophene) Pharmacology Clomiphene citrate is a weak synthetic estrogen that mimics the activity of an estrogen antagonist when given at typical pharmacologic doses for the induction of ovulation. It is cleared through the liver and excreted into the stool, with 85% clearance in 6 days. A functional hypothalamic–pituitary–ovarian axis is usually required for appropriate clomiphene citrate action. More specifically, clomiphene citrate is thought to bind and block estrogen receptors in the hypothalamus for prolonged periods, thereby decreasing the normal ovarian–hypothalamic estrogen feedback loop. This blockade increases GnRH pulsatility, leading to increased pituitary secretion of gonadotropins, which promote ovarian follicular development (136).
Clomiphene Citrate Outcomes Clomiphene is considered a first-line treatment for anovulatory infertility (147). Over the course of 6 months, clomiphene is associated with 49% ovulation, 23.9% pregnancy, and 22.5% live birth rates in women with anovulatory infertility (142).