Letrozole No Better Than Clomiphene for Unexplained Infertility

Women with unexplained infertility are commonly given clomiphene citrate or gonadotropins to stimulate multiple ovulations; however, aromatase inhibitors such as letrozole might reduce multiple gestations while maintaining live birth rates. NIH-funded investigators randomized 900 ovulatory women (age range, 18–40) with unexplained infertility and at least one patent fallopian tube to receive up to four cycles of ovarian stimulation with gonadotropin, clomiphene, or letrozole. The main goal was to determine if letrozole resulted in fewer multiple gestations and a similar live birth rate compared with standard therapy with clomiphene or gonadotropins.

Among ongoing pregnancies, the rate of multiple gestations with letrozole (9 of 67 pregnancies [13%]) did not differ significantly from that with gonadotropin or clomiphene (rate for these two groups combined, 42 of 192 [22%]; P=0.15) or clomiphene (8 of 85 [9%]; P=0.44) but was significantly lower than that with gonadotropin (34 of 107 [32%]; P=0.006). Notably, only twin pregnancies occurred with letrozole or clomiphene, whereas 10 triplet pregnancies occurred with gonadotropin. Live birth rates were similar among women who received letrozole (19%) or clomiphene (23%) but were significantly lower than among women who received gonadotropin (32%). In all groups, frequency of congenital anomalies was within the range expected for spontaneous pregnancies. Time to pregnancy and rates of pregnancy loss and neonatal complications did not differ significantly among groups.