Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial


Yarali H., Yildiz B., Demirol A., Zeyneloglu H., Yigit N., Bukulmez O., ...More

HUMAN REPRODUCTION, vol.17, no.2, pp.289-294, 2002 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 17 Issue: 2
  • Publication Date: 2002
  • Doi Number: 10.1093/humrep/17.2.289
  • Journal Name: HUMAN REPRODUCTION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.289-294
  • Keywords: insulin resistance, low-dose step-up protocol, metformin, polycystic ovary syndrome, rFSH, FOLLICLE-STIMULATING-HORMONE, INSULIN-RESISTANCE, OBESE WOMEN, GLUCOSE-TOLERANCE, INDUCED OVULATION, BINDING GLOBULIN, NORMAL MENSES, HYPERINSULINEMIA, THERAPY, HYPERANDROGENISM
  • Hacettepe University Affiliated: Yes

Abstract

BACKGROUND: This study aims to evaluate the impact of metformin on ovarian response when co-administered during recombinant (r)FSH using the low-dose step-up protocol in clomiphene citrate-resistant polycystic ovarian syndrome (PCOS) patients with normal glucose tolerance. METHODS AND RESULTS: Thirty-two patients were randomized to metformin (n = 16) and placebo (n = 16) groups. Hormonal assessment, a 75 g oral glucose tolerance test (OGTT) and a frequently sampled i.v. glucose tolerance test (FSIGTT) were performed before and after oral administration of metformin (850 mg twice daily) or placebo for 6 weeks. Recombinant FSH treatment was undertaken, thereafter, in women who did not ovulate on metformin (n = 10) or placebo (n = 15). There was no significant change in all insulin sensitivity indices in both groups. The only change noted was a decline in mean serum free testosterone concentration in the metformin group (P = 0.049). One patient on placebo and six patients on metformin ovulated spontaneously (P < 0.05). All parameters of ovarian response were comparable between the two groups during rFSH treatment. Combining the 6 week placebo or metformin-only period with a single rFSH treatment cycle, the overall ovulation rates were 75 and 94% in the placebo and metformin groups respectively (P > 0.05). The respective figures for pregnancy were 6.3 and 31.3% (P > 0.05). CONCLUSIONS: Metformin may restore ovulation with no improvement on insulin resistance in clomiphene citrate-resistant PCOS patients with normal glucose tolerance, but has no significant effect on ovarian response during rFSH treatment.