Metformin associated to clomiphene citrate for clomiphene citrate-resistant women with PCOS improves ovulatory and pregnancy rates. A randomized, double-blinded, placebo-controlled study

Abstract

OBJECTIVE: To evaluate the effect of metformin associated to clomiphene citrate (CC) on ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. MATERIALS AND METHODS: A total of 67 patients with PCOS who received 2 cycles of CC (100 mg/day from days 5 to 9) were initially included in the study. Patients who did not respond to CC were randomly allocated to receive either metformin 850 mg twice daily (group 1) or placebo twice daily (group 2) for two months. After that, CC (100 mg/day from days 5 to 9) was associated for the two following cycles, in both groups. Insulin, glucose, glucose/insulin ratio, testosterone, DHEAS, FSH, LH, body mass index (BMI), endometrial thickness, ovulation, and pregnancy rates were evaluated. RESULTS: A total of 36 patients were resistant to CC. In the metformin group, 15/21 (71.4%) women ovulated, and 8/21 (38.1%) conceived. In the control group, 5/15 (33.3%) women ovulated and 3/15 (20%) conceived. Compared with the control group, the metformin group had significantly higher ovulation (P = 0.04), however, there was no significant difference in the pregnancy rate between the two groups. When patients were separated according to BMI, we observed that obese patients (>28) had higher ovulation rates in the metformin group (11/12) than placebo group (2/8) (p=0.004). However this result was not observed for patients with BMI <28 (4/9 and 3/7 for metformin and placebo, respectively). CONCLUSIONS: Metformin associated to CC improves ovulation and pregnancy rates in clomiphene citrate-resistant women with PCOS, specially in obese patients.