Abstract
Two available groups of medications for ovulation induction are the oral selective estrogen receptor modulators, including clomiphene citrate and gonadotropins. Clomiphene is a well-tolerated, effective oral agent, but is known to have relatively common antiestrogenic endometrial and cervical mucus side effects that could prevent pregnancy despite successful ovulation. The available alternative after clomiphene citrate treatment failure usually includes gonadotropins, which are associated with several problems, including high cost, parenteral administration, necessity for sophisticated treatment monitoring to minimize the risk of severe ovarian hyperstimulation syndrome, and multiple pregnancy. Because of these problems, we proposed aromatase inhibition as a new method of ovulation induction. Others, as well as ourselves, have reported the success of letrozole, one of the third-generation aromatase inhibitors, in inducing and augmenting ovulation, in addition to other benefits associated with reducing the dose of gonadotropins required for ovarian stimulation, particularly in poor responders. The major advantages of letrozole, and possibly other aromatase inhibitors, include absence of persistent antiestrogenic effect owing to the short half-life (approximately 2 days) and lack of estrogen receptor depletion. This ensures a higher physiological estrogen concentration around the time of ovulation, with preservation of the hypothalamo–pituitary–ovarian axis leading to mono-follicular ovulation, which reduces the risk of multiple pregnancy. The current evidence suggests that aromatase inhibitors may replace clomiphene citrate and will become an integral part of other infertility treatments, in particular assisted reproduction. However, definitive studies, in the form of randomized controlled trials, are needed.