title: Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial.
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.
  
  
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Hacettepe University, Ankara, Turkey. yarali@ada.net.tr
authors.forename: Hakan
authors.initials: H
authors.lastname: Yarali
authors.forename: Bülent O
authors.initials: BO
authors.lastname: Yildiz
authors.forename: Aygül
authors.initials: A
authors.lastname: Demirol
authors.forename: Hulusi B
authors.initials: HB
authors.lastname: Zeyneloğlu
authors.forename: Nuray
authors.initials: N
authors.lastname: Yiğit
authors.forename: Orhan
authors.initials: O
authors.lastname: Bükülmez
authors.forename: Zehra
authors.initials: Z
authors.lastname: Koray
mesh_terms: D000328:Adult; D002996:Clomiphene / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D005640:Follicle Stimulating Hormone / Q000627:therapeutic use*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007333:Insulin Resistance; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D010060:Ovulation / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000503:physiopathology*; D011247:Pregnancy; D018873:Pregnancy Rate; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D013739:Testosterone / Q000097:blood
chemical_list: D005300:Fertility Agents, Female; D007004:Hypoglycemic Agents; D011994:Recombinant Proteins; D002996:Clomiphene; D013739:Testosterone; D005640:Follicle Stimulating Hormone; D008687:Metformin