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

ObjectiveTo compare the effect of letrozole with combined metformin and clomiphene citrate (CC) for ovulation induction in CC-resistant women with polycystic ovary syndrome (PCOS).DesignA randomized controlled trial.SettingUniversity 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 E2, 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.