title: Metformin improves pregnancy and live-birth rates in women with polycystic ovary syndrome (PCOS): a multicenter, double-blind, placebo-controlled randomized trial.
abstract: BACKGROUND
  The role of metformin in the treatment of infertility in women with polycystic ovary syndrome (PCOS) is still controversial. OBJECTIVE AND OUTCOMES: We investigated whether metformin decreases the early miscarriage rate and improves the pregnancy rates (PR) and live-birth rates (LBR) in PCOS.
  
  
  METHODS
  This was a multicenter, randomized (1:1), double-blind, placebo-controlled study. Three hundred twenty women with PCOS and anovulatory infertility were randomized to metformin (n = 160, Diformin; obese women, 1000 mg two times daily; nonobese subjects, 500 mg + 1000 mg daily) or identical doses of placebo (n = 160). After 3 months' treatment, another appropriate infertility treatment was combined if necessary. If pregnancy occurred, metformin/placebo was continued up to the 12th week.
  
  
  RESULTS
  Miscarriage rates were low and similar in the two groups (metformin 15.2% vs. placebo 17.9%, P = 0.8). Intent-to-treat analysis showed that metformin significantly improved PR and LBR (vs. placebo) in the whole study population (PR: 53.6 vs. 40.4%, P = 0.006; LBR: 41.9 vs. 28.8%, P = 0.014) and PR in obese women (49.0 vs. 31.4%, P = 0.04), and there was a similar trend in nonobese (PR: 58.6 vs. 47.6%, P = 0.09; LBR: 46.7 vs. 34.5%, P = 0.09) and in obese women with regard to LBR (35.7 vs. 21.9%, P = 0.07). Cox regression analysis showed that metformin plus standard infertility treatment increased the chance of pregnancy 1.6 times (hazard rate 1.6, 95% confidence interval 1.13-2.27).
  
  
  CONCLUSIONS
  Obese women especially seem to benefit from 3 months' pretreatment with metformin and its combination thereafter with routine ovulation induction in anovulatory infertility.
authors.affiliation: Department of Obstetrics and Gynaecology, University Hospital of Oulu PL 23, FIN-90029 Oys, Finland. lmp@cc.oulu.fi
authors.forename: Laure
authors.initials: L
authors.lastname: Morin-Papunen
authors.forename: Anni S
authors.initials: AS
authors.lastname: Rantala
authors.forename: Leila
authors.initials: L
authors.lastname: Unkila-Kallio
authors.forename: Aila
authors.initials: A
authors.lastname: Tiitinen
authors.forename: Maritta
authors.initials: M
authors.lastname: Hippeläinen
authors.forename: Antti
authors.initials: A
authors.lastname: Perheentupa
authors.forename: Helena
authors.initials: H
authors.lastname: Tinkanen
authors.forename: Risto
authors.initials: R
authors.lastname: Bloigu
authors.forename: Katri
authors.initials: K
authors.lastname: Puukka
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Juha S
authors.initials: JS
authors.lastname: Tapanainen
mesh_terms: D000022:Abortion, Spontaneous / Q000517:prevention & control*; D000328:Adult; D001723:Birth Rate; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D008687:Metformin / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000150:complications*; D011247:Pregnancy; D018873:Pregnancy Rate; D016896:Treatment Outcome
chemical_list: D008687:Metformin