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.