Gonadotropin-releasing hormone antagonist and metformin for treatment of polycystic ovary syndrome patients undergoing in vitro fertilization-embryo transfer

Gynecol Endocrinol. 2006 May;22(5):235-8. doi: 10.1080/14767050600761893.


Aim: The combination of gonadotropin-releasing hormone (GnRH) antagonist and gonadotropin represents a valid alternative to the classical protocol with GnRH agonist for ovulation induction in patients with polycystic ovary syndrome (PCOS). The use of metformin is of benefit to women with PCOS. The aim of the present study was to compare the stimulation characteristics and in vitro fertilization (IVF)-embryo transfer (ET) outcomes of the standard short GnRH antagonist protocol for ovarian stimulation with or without metformin.

Materials and methods: We recruited 40 PCOS patients. The population studied was divided into two groups (A and B). Group A was pretreated for 2 months with metformin 1.5 g/day (Glucophage(R); Merck Pharm), and then stimulated with recombinant follicle-stimulating hormone (rFSH) 150 UI/day (Gonal F(R) 75 UI; Serono). GnRH antagonist, cetrorelix acetate 0.25 mg/day (Cetrotide(R); Serono), was started when the leading follicle reached 14 mm diameter on ultrasound scan. Group B was treated only with rFSH 150 UI/day and GnRH antagonist 0.25 mg/day when the leading follicle was >or=14 mm in diameter.

Results: In group A we found a statistically significant (p < 0.05) decrease in the number of ampoules of rFSH (A vs. B: 18+/-6 vs. 24+/-8) and estradiol levels (A vs. B: 2400+/-600 vs. 3370+/-900 pg/ml) (all values mean+/-standard deviation). Group A had significantly fewer cancelled cycles (A vs. B: 1 vs. 3; p < 0.05). The incidence of ovarian hyperstimulation syndrome was 5% in group A and 15% in group B (p < 0.05). In patients treated with metformin, the total number of follicles on the day of human chorionic gonadotropin treatment (23+/-1.2 vs. 33+/-2.6) was decreased with no change in the number of follicles >or=14 mm in diameter (A vs. B: 18+/-1.2 vs. 19+/-1.7). However, the mean number of mature oocytes (A vs. B: 8.4+/-1.5 vs. 5.0+/-1.5) was increased with metformin treatment (p < 0.05). No difference was found in the number of cleaved embryos (A vs. B: 2.5+/-0.5 vs. 2.2+/-0.3).

Conclusions: The use of metformin with GnRH antagonist improves the outcome of ovarian stimulation in IVF-ET cycles in PCOS patients.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Chorionic Gonadotropin / administration & dosage
  • Estradiol / blood
  • Female
  • Fertilization in Vitro
  • Follicle Stimulating Hormone / administration & dosage
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Infertility, Female / therapy*
  • Metformin / therapeutic use*
  • Ovarian Hyperstimulation Syndrome / epidemiology
  • Ovulation Induction / methods*
  • Polycystic Ovary Syndrome / complications*
  • Polycystic Ovary Syndrome / drug therapy
  • Recombinant Proteins / administration & dosage
  • Treatment Outcome


  • Chorionic Gonadotropin
  • Hypoglycemic Agents
  • Recombinant Proteins
  • Gonadotropin-Releasing Hormone
  • Estradiol
  • Follicle Stimulating Hormone
  • Metformin