title: Metformin treatment before IVF/ICSI in women with polycystic ovary syndrome; a prospective, randomized, double blind study.
abstract: BACKGROUND
  Our aim was to investigate the effect of pre-treatment with metformin in women with polycystic ovary syndrome (PCOS) scheduled for IVF stimulation.
  
  
  METHODS
  Seventy-three oligo/amenorrhoeic women with polycystic ovaries and at least one of the following criteria: hyperandrogenaemia, elevated LH/FSH ratio, hyperinsulinism, decreased SHBG levels or hirsutism, were studied. Normal weight and overweight patients were randomized separately in a prospective, randomized, double blind study. All patients were treated for at least 16 weeks with metformin (1000 mg bid) or placebo ending on the day of HCG injection.
  
  
  RESULTS
  No differences were found in the primary end-points: duration of FSH stimulation 14.4 (13.1-15.7) versus 14.2 (12.6-15.7) days or estradiol on the day of HCG injection 6.8 (5.3-8.2) versus 7.6 (5.6-9.6) nmol/l in the metformin and placebo groups, respectively. The secondary end-points number of oocytes, fertilization rates, embryo quality, pregnancy rates and clinical pregnancy rates were equal. However, in the normal weight subgroup (BMI <28 kg/m(2), n = 27), pregnancy rates following IVF were 0.71 (0.63-0.79) versus 0.23 (0.15-0.31) in the metformin and placebo groups, respectively (P = 0.04). Overall clinical pregnancy rates were equal: 0.51 (0.34-0.68) versus 0.44 (0.27-0.62) in the metformin and placebo groups, respectively. However, in the normal weight subgroup, clinical pregnancy rates were 0.67 (0.43-0.91) and 0.33 (0.06-0.60), respectively (P = 0.06).
  
  
  CONCLUSIONS
  Pre-treatment with metformin prior to conventional IVF/ICSI in women with PCOS does not improve stimulation or clinical outcome. However, among normal weight PCOS women, pre-treatment with metformin tends to improve pregnancy rates. Further studies in subgroups of PCOS women are required.
authors.affiliation: Department of Obstetrics and Gynaecology, Trondheim University Hospital, Trondheim, Norway. sigrun.kjotrod@c2i.net
authors.forename: S B
authors.initials: SB
authors.lastname: Kjøtrød
authors.forename: V
authors.initials: V
authors.lastname: von Düring
authors.forename: S M
authors.initials: SM
authors.lastname: Carlsen
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005306:Fertilization; D005307:Fertilization in Vitro; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D018873:Pregnancy Rate; D011292:Premedication; D011446:Prospective Studies; D020554:Sperm Injections, Intracytoplasmic; D015431:Weight Loss
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin