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

Hakan Yarali, Bülent O. Yildiz, Aygül Demirol, Hulusi B. Zeyneloǧlu, Nuray Yiǧit, Orhan Bükülmez, Zehra Koray

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)289-294
Number of pages6
JournalHuman Reproduction
Volume17
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Insulin resistance
  • Low-dose step-up protocol
  • Metformin
  • Polycystic ovary syndrome
  • rFSH

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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