Metformin effects on clomifene-induced ovulation in the polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common, complex endocrine disorder for women on reproductive age. A high incidence of ovulation failure is observed in PCO women and perhaps linked to insulin resistance related to metabolic features In the last few years some studies assessed hyperinsulinimea and insulin resistance attenuation effects, by insulin sensitizing agents such as metformin, in PCOS women suggesting potential scope for these drugs in CC ovulation induction quality improvement.

Our prospective study aim is to compare the effectiveness of clomifene citrate plus metformin and clomifene citrate plus placebo in women with newly diagnosed polycystic ovary syndrome.

From February 24 to September 29 (2007), PCOS was explored on women attending the Department of Obstetrics & Gynaecology sterility consultation unit (CHU Hedi Chaker-Sfax) according to the Rotterdam 2003 diagnostic criteria. PCOS patients were randomized to receive, in addition to clomifene citrate treatment, placebo or metformin 850 mg two times a day all ovulatory cycle for three trials maximum. Ovulation detection was done by the E2 serum measurements and ovarian transvaginal ultrasonography' evolution controlling on 7th, 11th and 13th day of the cycle.

Within 7 months, 32 PCOS women were recruited in the study and equally allocated to the two groups. Baseline characteristics were similar in metformin group and placebo one. Ovulation was characterized by the presence of at least one mature follicle (> 16 mm), a circulating estradiol concentration in the edge of 150-250 pg and accessory an endometrial depth > 8 mm. The ovulation rate in the metformin group was 62.5% compared with 37.5% in the placebo group, a non-statistically significant (small study population) but important difference (1.66 times). Analyses show a higher mature follicle number and estradiol concentration in metformin group than in the placebo one. Metformin effect was, in our study, his only insulinosensitizer property consequence far away a 'making thinner' or Hyperandrogenism reducing ones.

The ovulatory response to clomifene can be increased in polycystic ovary syndrome women by decreasing insulin secretion with metformin.