Zain 2009.

Methods	RCT Setting: Malaysia  Method of randomisation: picking a card out of a box  Blinding: unblinded Number randomised: 124
Participants	Summary: metformin and CC vs CC vs metformin in obese PCOS  Inclusion criteria: newly diagnosed with PCOS (Rotterdam criteria), age < 40 years Exclusion criteria: diabetes, hepatic or renal dysfunction, heart disease, abnormal semen analysis (WHO criteria)  Baseline characteristics of each group: metformin and CC vs CC vs metformin mean age (SD) 29.3 (4.9), 29.6 (4.3), 27.8 (3.6) mean BMI (SD) 33.0 (4.1), 32.9 (4.2), 33.9 (3.6) mean total testosterone nmol/L (SD) 0.77 (0.14), 0.41 (0.45), 0.57 (0.1) Dropouts: 4 (9.5%) in the metformin group, 2 (4.9%) in the CC group and 3 (7.3%) in the combined metformin and CC group
Interventions	Main intervention: metformin 1500 mg/d  Duration: 6 months  Co‐interventions: CC 50 mg from day 2‐6 of the cycle. If women did not respond to the treatment, the dose increased by 50 mg to a maximum dose of 200 mg All the women were offered dietary advice.
Outcomes	Primary: live birth rate Secondary: clinical pregnancy, ovulation: USS follicular tracking, testosterone, miscarriage, multiple pregnancy
Notes	This study was designed to compare the live birth rates in women who received CC, metformin and combined CC and metformin treatments. Placebo tablets were not used in this unblinded RCT. Therefore, potential bias may be introduced.  Most women were Malay (about 90%) Analysis was based on analysis per protocol, not ITT
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Picking a card out of a box labelled A, B or C for metformin, CC and metformin and CC respectively
Allocation concealment (selection bias)	High risk	No information
Blinding of participants and personnel (performance bias) All outcomes	High risk	Unblinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	Unblinded
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropouts: 4 (9.5%) in the metformin group, 2 (4.9%) in the CC group and 3 (7.3%) in the combined metformin and CC group. Details not reported. Analysis was based on analysis per protocol, not ITT
Selective reporting (reporting bias)	Unclear risk	Insufficient information in the study
Other bias	Low risk	No evidence of other bias

Baseline characteristics given in order of main intervention (drug, placebo).

Where the trial protocol included a statement such as, "all patients had ultrasound features of PCOS" then this has been included as an inclusion criteria (unless the study authors specifically state that it was not in which case it is recorded under notes).

Abbreviations Table 4:

BMI: body mass index; CAH: congenital adrenal hyperplasia; CC: clomiphene citrate; CI: confidence interval; CSH: chorionic somatomammotropin hormone; CT: computerised tomography scan; DHEAS: dehydroepiandrosterone sulphate; FAI: Free Androgen Index; FSH: follicle‐stimulating hormone; HSG: hysterosalpingogram; IQR: interquartile range; ITT: intention‐to‐treat; IVF: in vitro fertilisation; LH: luteinizing hormone; LOD: laparoscopic ovarian drilling; OGTT: Oral glucose tolerance test; OHSS: ovarian hyperstimulation syndrome; RCT: randomised controlled trial; rFSH: recombinant follicle‐stimulating hormone; PCO(S): polycystic ovary (syndrome); SD: standard deviation
 SE(M): standard error of the mean; TFT: thyroid function test; TSH: thyroid‐stimulating hormone; US(S): ultrasound (scan); WHO: World Health Organization