title: Does metformin affect the ovarian response to gonadotropins for in vitro fertilization treatment in patients with polycystic ovary syndrome and reduced ovarian reserve? A randomized controlled trial.
abstract: OBJECTIVE
  To evaluate the effects of metformin on the ovarian response to gonadotropins given for in vitro fertilization (IVF) programs in patients with polycystic ovary syndrome (PCOS) and reduced ovarian reserve.
  
  
  METHODS
  Prospective, parallel, randomized, double-blind, placebo-controlled clinical trial.
  
  
  METHODS
  Academic departments of obstetrics and gynecology, and a private IVF center.
  
  
  METHODS
  Primary infertile patients with PCOS older than 35 years and/or with a basal follicle-stimulating hormone (FSH) level higher than 10 IU/L who were scheduled for IVF cycles.
  
  
  METHODS
  Gonadotropin-releasing hormone agonist flare-up protocol and high starting doses of recombinant FSH plus metformin or placebo tablets.
  
  
  METHODS
  Primary end point: cancellation rate for low ovarian response. Secondary end-points: other clinical, biochemical, and reproductive data.
  
  
  RESULTS
  Enrollment was stopped after 88 participants had been randomized and analyzed due to an unacceptable increased risk of poor ovarian response in the metformin arm. Statistically significant differences between the metformin and placebo groups were observed in the dose of gonadotropins used, peak estradiol levels, and the number of dominant follicles, retrieved oocytes, and metaphase II oocytes.
  
  
  CONCLUSIONS
  In patients with PCOS and reduced ovarian reserve, metformin worsened the response to gonadotropins, and its administration should be stopped before the start of controlled ovarian hyperstimulation for IVF programs. CLINICAL TRIALS IDENTIFICATION NUMBER: NCT01208740.
authors.affiliation: Department of Obstetrics and Gynecology, University Magna Graecia of Catanzaro, Catanzaro, Italy. stefanopalomba@tin.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Palomba
authors.forename: Angela
authors.initials: A
authors.lastname: Falbo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Di Cello
authors.forename: Fulvio
authors.initials: F
authors.lastname: Cappiello
authors.forename: Achille
authors.initials: A
authors.lastname: Tolino
authors.forename: Fulvio
authors.initials: F
authors.lastname: Zullo
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D005307:Fertilization in Vitro; D006062:Gonadotropins / Q000627:therapeutic use*; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007558:Italy; D008687:Metformin / Q000009:adverse effects*; D010053:Ovary / Q000187:drug effects* / Q000503:physiopathology; D010060:Ovulation / Q000187:drug effects*; D010062:Ovulation Induction / Q000379:methods*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D018873:Pregnancy Rate; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D005300:Fertility Agents, Female; D006062:Gonadotropins; D008687:Metformin