O-29: Pregnancies Following the Use of SequentialTreatment of Metformin and IncrementalDoses of Letrozole in Clomiphen-ResistantWomen with Polycystic Ovary Syndrome

Background: Clomiphen citrate (CC) is the first line therapy for women with infertility and poly cystic ovary syndrome( PCOS).However, 20-25% of women are resistant to CC and do not ovulate. The Background of this study is to evaluate the efficacy of sequential treatment of metformin and incremental doses of letrozole in induction of ovulation in cases of clomiphen citrateresistant (CC- R) PCOS patients and to determine in which doses of letrozole the maximum response would occur. Materials and Methods: In this prospective trial, we enrolled 106 anovulatory PCOS women who failed to ovulate with CC alone from Amir-Almomenin University General Hospital in Semnan, Iran. After an initial 6-8 weeks of metformin treatment, they received 2.5mg letrozole for 5 days starting from day 3 of their menstrual cycle. If they did not ovulate with 2.5mg letrozole, the doses were increased to 5 to7.5 mg daily in subsequent cycles. The main outcomes were ovulatory and pregnancy rates in different doses of letrozole and cumulative pregnancy rate at the end of treatment.Results: 14 of 105 patients (13.33%) conceived with metformin alone. The remaining 91 patients who did not conceive with metformin continued metformin and letrozole was started for them. Ovulation occurred in 83 out of 91 patients (91.2%) and maximum ovulation occurred in 2.5mg (40.65%) and 5mg (37.36%) doses of letrozole respectively .Only 13.8%of ovulation ocurred in 7.5 mg letrozole. In the end, 8 out of 91 patients (8.79%) remained anovulatory. Cumulative pregnancy rate was 60/105 (57.14%) with 45 out of 60 (74.9%) pregnancies being full term. Conclusion: Combination of metformin with incremental doses of letrozole is associated with a good pregnancy rate in CC-resistant PCOS patients.