Palomba 2005a.

Methods	RCT  Setting: Italy Method of randomisation: computer‐generated random allocation sequence in double block Blinding: double  Number randomised: 100
Participants	Summary: metformin vs CC in non‐obese PCOS  Inclusion criteria: National Institutes of Health criteria, age 20‐34 years, BMI < 30 kg/m2, tubal patency confirmed by HSG:, normal semen analysis Exclusion criteria: metabolic disorders, hepatic or renal dysfunction, thyroid disease, hyperprolactinaemia, Cushing's syndrome, CAH, hormonal drugs, pelvic diseases, previous pelvic surgery Baseline characteristics of each group: metformin (n = 45) vs CC (n = 47) mean age (SD) 26.4 (2.9), 25.9 (2.7) mean BMI (SD) 27.0 (2.9), 26.7 (2.8) mean fasting  insulin mIU/L (SD) 19.5 (5.4), 20.4 (5.6) mean total testosterone mol/L (SD) 3.12 (1.04), 3.47 (1.0) Dropouts: 5 in the metformin group and 3 in the metformin + CC group
Interventions	Main intervention: metformin 850 mg twice daily and placebo vs CC 150 mg on day 3‐7 of the cycle and placebo Duration: 6 months  Co‐interventions: none
Outcomes	Primary: live birth rate, gastrointestinal side effects Secondary: clinical pregnancy rate, menstrual frequency, ovulation: USS follicular tracking, miscarriage, multiple pregnancy, other adverse effects: various pregnancy complications
Notes	This study was designed to compare the effectiveness of metformin and CC treatment as a first‐line therapy in non‐obese anovulatory women with PCOS.  The primary end point measure was the pregnancy rate.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random allocation sequence in double block
Allocation concealment (selection bias)	Unclear risk	Allocation sequence concealed until the interventions were assigned
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Inadequate information
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Inadequate information
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dropouts: 5 in the metformin group and 3 in the metformin + CC group with reasoning
Selective reporting (reporting bias)	Unclear risk	Insufficient information in the study
Other bias	Low risk	No evidence of other bias