In women with polycystic ovary syndrome (PCOS), the aromatase inhibitor letrozole (Femara) results in better pregnancy outcomes than the current first-line treatment clomiphene (Clomid), according to a new study. Researchers randomly assigned 750 women with PCOS to letrozole or clomiphene for up to five treatment cycles with the primary outcome of live birth during the treatment period. Women treated with letrozole had more cumulative live births than those receiving clomiphene (27.5% vs 19.1%, P = 0.007) with no significant differences in congenital abnormalities (although there were four major congenital abnormalities in the letrozole group and one in the clomiphene group). The cumulative ovulation rate was higher with letrozole (61.7% vs 48.3%, P < 0.001). There was no difference in the rate of pregnancy loss or rate of twins, and side effects were slightly different (more hot flushes with clomiphene and more fatigue and dizziness with letrozole), although there was no difference in incidence of side effects. The authors conclude that, compared to clomiphene, letrozole was associated with higher live-birth and ovulation rates among women with PCOS. The safety and teratogenic risks with letrozole compared to other infertility therapies need further study (N Engl J Med 2014;371:119-129).