Letrozole versus combined metformin and clomiphene citrate for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a randomized controlled trial

Objective: To compare the effect of letrozole with combined metformin and clomiphene citrate (CC) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS). Design: A randomized controlled trial. Setting: University teaching hospital and a private practice setting. Patient(s): Two hundred fifty anovulatory women (582 cycles) with CC-resistant PCOS. Intervention(s): Patients received 2.5 mg of letrozole daily (123 patients, 285 cycles) or combined metformin-CC (127 patients, 297 cycles) for three treatment cycles. Main Outcome Measure(s): Ovulation rate, number of follicles, serum E-2, serum P, endometrial thickness, pregnancy, and miscarriage rates. Result(s): Ovulation occurred in 185/285 cycles (64.9%) in the letrozole group versus 207/297 cycles (69.6%) in the combined metformin-CC group, without statistically significant difference. The total number of follicles was significantly more in the combined metformin-CC group (4.4 +/- 0.4 vs. 6.8 +/- 0.3). A nonsignificant increase in endometrial thickness on the day of hCG administration was observed in the letrozole group (9.5 +/- 0.2 mm vs. 9.1 +/- 0.1 mm). No statistically significant difference regarding the pregnancy rate (PR) was observed between both groups (14.7% vs. 14.4%). Conclusion(s): Letrozole and combined metformin-CC are equally effective for inducing ovulation and achieving pregnancy in patients with CC-resistant PCOS. (Fertil Steril (R) 2010;94:1405-9. (C) 2010 by American Society for Reproductive Medicine.)