Metformin reduces risk of ovarian hyperstimulation syndrome in patients with polycystic ovary syndrome during gonadotropin-stimulated in vitro fertilization cycles: a randomized, controlled trial

Fertil Steril. 2011 Dec;96(6):1384-1390.e4. doi: 10.1016/j.fertnstert.2011.09.020. Epub 2011 Oct 7.


Objective: To test whether metformin administration reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in infertile high-risk patients with polycystic ovary syndrome (PCOS) who have been treated with gonadotropins for IVF.

Design: Parallel, randomized, double-blind, placebo-controlled clinical trial.

Setting: Academic departments, general hospital, and IVF centers.

Patient(s): One hundred twenty patients with PCOS at high risk for OHSS.

Intervention(s): Gonadotropins ovarian stimulation for IVF and metformin (500 mg three times daily) or placebo tablets (three times daily).

Main outcome measure(s): The primary end point of the current clinical trial was the rate of OHSS. Anthropometric and reproductive data were evaluated.

Result(s): The total OHSS and cancellation rates were significantly reduced in patients treated with metformin. The relative risk for OHSS was of 0.28 (95% confidence interval, 0.11-0.67). With metformin the stimulation length and the total amount of gonadotropins used were significantly increased, whereas the peak E(2) levels were significantly reduced.

Conclusion(s): In patients with PCOS who are at high risk for OHSS and who have been stimulated with gonadotropins for IVF cycles, metformin reduces the risk of OHSS by modulating the ovarian response to the stimulation. REGISTRATION ID NUMBER FROM CLINICALTRIALS.GOV: NCT01233206.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Down-Regulation / drug effects
  • Drug Administration Schedule
  • Female
  • Fertilization in Vitro* / methods
  • Gonadotropins / therapeutic use*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Metformin / administration & dosage
  • Metformin / pharmacology
  • Metformin / therapeutic use*
  • Ovarian Hyperstimulation Syndrome / epidemiology
  • Ovarian Hyperstimulation Syndrome / etiology
  • Ovarian Hyperstimulation Syndrome / prevention & control*
  • Ovulation Induction / methods
  • Placebos
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Risk Factors


  • Gonadotropins
  • Hypoglycemic Agents
  • Placebos
  • Metformin

Associated data