Human Reproduction, Vol. 17, No. 2, 289-294,
February 2002
© 2002 European Society of Human Reproduction and Embryology
Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial
lu3it11 Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, 2 Department of Internal Medicine, Division of Endocrinology, Faculty of Medicine, Hacettepe University and 3 Department of Obstetrics and Gynecology, Faculty of Medicine, Basikent University and 4 Department of Nuclear Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey
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.
Key words: insulin resistance/low-dose step-up protocol/metformin/polycystic ovary syndrome/rFSH
5 To whom correspondence should be addressed at: Hafta sokak, No. 23/4, Gaziosmanpasia 06700 Ankara, Turkey. E-mail: hyarali{at}hacettepe.edu.tr or yarali{at}ada.net.tr
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