De Leo V1, La Marca A, Ditto A, Morgante G, Cianci A. Abstract OBJECTIVE: To evaluate whether pretreatment with metformin improves FSH-induced ovulation in women with clomiphene-resistant polycystic ovary syndrome (PCOS). DESIGN: Randomized prospective trial. SETTING: Department of Obstetrics and Gynecology, University of Siena. PATIENT(S): Twenty women with clomiphene citrate-resistant PCOS. INTERVENTION(S): The women were divided randomly into groups A and B (10 subjects each). Group B received 1,500 mg of metformin for at least a month before a single cycle of FSH stimulation. Group A underwent two cycles of FSH stimulation and then received metformin for a month before undergoing a third cycle. MAIN OUTCOME MEASURE(S): The number of FSH ampules, days of treatment, E2 level on the day of hCG, number of follicles > 15 mm, number of hyperstimulation, and the number of cycles with hCG withheld. RESULT(S): The number of follicles > 15 mm in diameter on the day of hCG administration was significantly lower in cycles performed after metformin treatment. The percentage of cycles with hCG withheld because of excessive follicular development was significantly lower in cycles treated with metformin. Plasma levels of E2 were significantly higher in cycles treated with FSH alone than in those treated with FSH and metformin. CONCLUSION(S): By reducing hyperinsulinism, metformin determines a reduction in intraovarian androgens. This leads to a reduction in E2 levels and favors orderly follicular growth in response to exogenous gonadotropins.