Effects of Metformin on Ovulation and Pregnancy Rate in Women with Clomiphene Resistant Poly Cystic Ovary Syndrome

Document Type : Original Article


1 Endocrinology and Female Infertility Department, Royan Institute

2 Obstetrics and Gynecology Department, Faculty of Medicine, Iran University of Medical Sciences, Akbar Abadi Hospital

3 Epidemiology Department, Royan Institute


Background: To evaluate the effect of metformin on ovulation and pregnancy rate in clomiphene citrate resistant women with polycystic ovary syndrome (PCOS).
Material & Methods: In this clinical trial each patient, regarding her previous resistance to Clomiphene, served as her own control. A total of 35 clomiphene citrate resistant PCOS patients, referring to Royan institute were studied. Clomiphene citrate resistance was defined as having failure of ovulation during at least three cycles using clomiphene citrate doses up to 200 mg/day on cycle days 3-7 after a withdrawal bleeding with progesterone. Metformin was used alone or in combination with clomiphene citrate. First, the patients received metformin up to 1500 mg/day for 8 weeks. During the next 2-3 cycle if the patients did not become pregnant, clomiphene was added with increments of 100 mg (up to 150 mg/day). Follicular development and ovulation were monitored by ultrasound scans and mid-luteal progesterone level. Menstrual pattern, ovulation, and pregnancy rate were evaluated during the two stages of treatment.
Results: After 8 weeks of meformin monotherapy, ovulation occurred in 23 cases (65.7%) and 7 patients (20%) became pregnant. Among other patients (28/35) who were treated with Clomiphene Citrate and metformin for 64 cycles, 19 patients (67.8%) had proper ovulation and five of them (17.8%) became pregnant. Totally, metformin induced ovulation in 31 of 35 patients (88.6%) and twelve (34.3%) of them achieved pregnancy.
Conclusion: Metformin alone or in combination with clomiphene is a very effective treatment in inducing ovulation and pregnancy in clomiphene resistant women with PCOS.