The use of metformin for women with PCOS undergoing IVF treatment

Hum Reprod. 2006 Jun;21(6):1416-25. doi: 10.1093/humrep/del025. Epub 2006 Feb 24.


Background: Metformin appears to improve reproductive function in some women with polycystic ovary syndrome (PCOS). We wished to explore the effect of metformin in women with PCOS undergoing IVF.

Methods: A randomized, placebo-controlled, double-blind study was carried out between 2001 and 2004. Patients with PCOS undergoing IVF/ICSI treatment using a long GnRH agonist protocol were randomized to receive metformin (MET), 850 mg, or placebo (PLA) tablets twice daily from the start of the down-regulation process until the day of oocyte collection. The primary outcome was to be an improvement in the overall fertilization rate.

Results: One-hundred and one IVF/ICSI cycles were randomized to receive metformin (52) or to receive placebo (49). There was no difference in the total dose of rFSH required per cycle (median dose: MET = 1200 U, PLA = 1300 U; P = 0.937). The median number of oocytes retrieved per cycle (MET = 17.2, PLA = 16.2; P = 0.459) and the overall fertilization rates (MET = 52.9%, PLA = 54.9%; P = 0.641) did not differ. However, both the clinical pregnancy rates beyond 12 weeks gestation per cycle (MET = 38.5%, PLA = 16.3%; P = 0.023) and per embryo transfer (MET = 44.4%, PLA = 19.1%; P = 0.022) were significantly higher in those treated with metformin. Furthermore, a significant decrease in the incidence of severe ovarian hyperstimulation syndrome (OHSS) was observed (MET = 3.8%, PLA = 20.4%; P = 0.023), and this was still significant after adjustment for BMI, total rFSH dose and age (OR = 0.15; 95% CI: 0.03, 0.76; P = 0.022).

Conclusion: Short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Female
  • Fertilization in Vitro / methods*
  • Follicle Stimulating Hormone / therapeutic use
  • Gonadotropin-Releasing Hormone / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin / therapeutic use*
  • Odds Ratio
  • Placebos
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Pregnancy Rate
  • Time Factors
  • Treatment Outcome


  • Hypoglycemic Agents
  • Placebos
  • Gonadotropin-Releasing Hormone
  • Follicle Stimulating Hormone
  • Metformin