Morin‐Papunen 2012.

Methods	Multicentre RCT (parallel‐group study) Setting: Finland Method of randomisation: randomisation codes remained concealed. Metformin and placebo identically packaged and consecutively numbered Blinding: double Number randomised: 320
Participants	Summary: metformin vs placebo Inclusion criteria: PCOS diagnosed by Rotterdam criteria, anovulatory infertility for at least 6 months and 3 months since the last infertility treatment. Age range 18‐39 years Exclusion criteria: type 1 diabetes mellitus, liver, cardiac or renal disease, hormone medication, alcohol use, regular smoking Baseline characteristics of each group metformin vs placebo mean age (SD) 28.4 (3.9), 27.9 (4.1) mean BMI (SD) 27.1 (6.3), 27.4 (6.2) mean fasting insulin, microIU/mL (SD) 11.0 (11.2), 11.4 (11.8) testosterone, ng/dL (SD) 43.2 (17.3), 45.8 (20.2) mean fasting glucose, mg/dL (SD) 91.9 (7.2), 91.9 (9.0) Dropouts: 61 women were lost to follow‐up or discontinued but their data were included in the ITT analysis
Interventions	Main intervention: metformin 500 mg 1/d for 1 week, then increased weekly by 1 extra tablet/d to 1.5 g/d in non‐obese and 2 g/d in obese women versus placebo Duration: 3‐9 months Co‐interventions: if pregnancy had not occurred by 3 months, ovulation induction was started with CC. If unsuccessful after 4‐6 cycles, gonadotrophins or aromatase inhibitors were used
Outcomes	Primary: live birth rate, gastrointestinal side effects Secondary: clinical pregnancy rate, BMI, miscarriage rate
Notes	This study was to ascertain the effects of metformin on pregnancy and live birth rates. Endocrine/metabolic outcomes not measured. Additional information sought from the study authors
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Performed by hospital pharmacy with 1:1 allocation in random blocks of 10 using computer‐generated lists
Allocation concealment (selection bias)	Low risk	Metformin and placebo identically packaged and consecutively numbered. Randomisation codes remained blinded until database lock had taken place.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and personnel were blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigators were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	61 women were lost to follow‐up or discontinued but their data were included in the ITT analysis
Selective reporting (reporting bias)	Unclear risk	Insufficient information in the study
Other bias	Low risk	No evidence of other bias