Fedorcsak 2003

Methods	Generation of the allocation sequence: table of random numbers Allocation concealment method: sealed, opaque envelopes serially numbered Blinding method: does not apply (open‐label cross‐over trial) Number and reasons for withdrawals: not reported ITT analysis: yes Prospective, open‐label, randomised cross‐over trial. Only data from the pre‐cross‐over phase of this study were considered for meta‐analysis Women were randomised to receive 2 consecutive cycles: metformin versus no treatment (control) ‐ no treatment versus metformin
Participants	17 PCOS participants were randomised (9 in the metformin group and 8 in the placebo group) Diagnosis of PCOS followed the Rotterdam criteria (ESHRE/ASRM). All participants had insulin‐resistance, based on an insulin resistance index Exclusion criteria: a) congenital adrenal hyperplasia b) Cushing's syndrome c) androgen‐producing tumours d) hyperprolactinaemia Age: 23 to 35 years (median 31) The causes of infertility were not reported Only the first arm was compared: 8 participants in the no treatment group versus 9 participants in the metformin group
Interventions	Metformin 500 mg tid was started 3 weeks before down‐regulation with GnRH‐agonist began and continued until the day of hCG injection Protocol for controlled ovarian hyperstimulation: long luteal phase pituitary down‐regulation using the GnRH analogue buserelin acetate 600 μg (Suprefact®) with step‐up rec‐FSH (Gonal F® ‐ starting dose 150 IU). hCG (Profasi® 10000 IU) was administered when at least 2 follicles were larger than 18 mm. Oocyte retrieval was performed within 34 to 38 hrs of hCG injection Assisted reproductive technology (ART): IVF or ICSI Embryo transfer: maximum of 2 embryos were transferred per participant on day 3 after oocyte retrieval Catheter used for transfer: not reported Luteal phase support: intramuscular progesterone (25 mg/day) until day 14 after follicle puncture
Outcomes	Primary outcomes: a) total dose of FSH given during stimulation b) number of collected oocytes Secondary outcomes: a) number of days of gonadotrophin b) fertilisation rate c) number of embryos transferred d) pregnancy rate per woman e) miscarriage rate f) incidence of OHSS d) incidence of adverse side effects
Notes	Country of the study: Norway
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Adequate ‐ random numbers table
Allocation concealment (selection bias)	Low risk	Adequate ‐ sealed, opaque envelopes serially numbered
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label cross‐over trial
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no withdrawals in the phase analysed (pre‐cross‐over phase)
Selective reporting (reporting bias)	Unclear risk	Live birth rate was not evaluated
Other bias	Unclear risk	No power calculation. The causes of infertility were not reported