Ovulation Induction with Letrozole and Clomiphene

Mechanism of Action

Letrozole is an aromatase inhibitor that blocks the conversion of androgens to estrogens in peripheral tissues, thereby reducing circulating estrogen levels, which in turn increases FSH secretion and stimulates follicular development in women with polycystic ovary syndrome (PCOS) 2
Clomiphene citrate is a selective estrogen receptor modulator (SERM) that competitively binds to estrogen receptors in the hypothalamus and pituitary, preventing endogenous estrogen from exerting its normal negative feedback, and thereby increasing gonadotropin (FSH and LH) release in response to perceived low estrogen in women with ovulatory dysfunction 1

The American College of Obstetricians and Gynecologists (ACOG) still recommends clomiphene citrate as first-line treatment for ovulation induction based on its long-established safety profile, though this recommendation predates the strongest letrozole data, with approximately 80% of women with PCOS ovulating and half of those who ovulate conceiving 3, 4
Letrozole produces superior pregnancy outcomes compared to clomiphene, with higher pregnancy rates, shorter time to conception, and more monofollicular development, making it a viable alternative for ovulation induction in women with PCOS 2, 5