Letrozole (Femara)

Letrozole blocks aromatase, the enzyme that converts androgens to estrogen. Lower estrogen reduces negative feedback on the hypothalamus, prompting FSH release and follicle recruitment. Unlike clomiphene, it does not deplete estrogen receptors, so cervical mucus and endometrial lining are usually better preserved.

Multiple randomized trials — including a major NICHD network study — show letrozole produces higher ovulation rates, pregnancy rates, and live birth rates than clomiphene in women with PCOS. It is now considered first-line for ovulation induction in PCOS in most fertility guidelines. Standard dosing is 2.5–7.5 mg on cycle days 3–7. It can also be used with IUI or gonadotropins in mild stimulation protocols.