Sohrabvand 2006.

Study characteristics
Methods	Single‐blinded randomised clinical trial Duration and location of the trial: quote: "In this single‐blind randomized clinical trial, 120 ovarian cycles were studied in 60 clomiphene‐resistant patients with PCOS, who were chosen among 115 PCOS patients attending the infertility clinic of Vali‐e‐Asr Hospital (Tehran, Iran) during the years 2003–2004.“
Participants	Inclusion criteria: women with PCOS who had failed to become pregnant after 3 courses of 150 mg CC (considered as CC‐resistant), whereas the values of hormonal tests were normal. Tests: thyroid function, prolactin level, hysterosalpingography and husband’s sperm analysis Exclusion criteria: women with a history of liver and kidney failure, cardiovascular disease, diabetes (based on criteria set by the American Diabetic Association) or women who consumed metformin or drugs affecting insulin secretion or CC in the previous 2 months Number of centres: 1, infertility clinic of Vali‐e‐Asr Hospital, Tehran Number of women randomised: 60; group A metformin‐letrozole: 30, group B metformin‐CC: 30 Number of women analysed: group A metformin‐letrozole: 29, group B metformin‐CC: 30 Number of withdrawals/exclusions/loss to follow‐up and reasons: 1 because she got pregnant after metformin treatment before letrozole was started Age (y): group A metformin‐letrozole: 28.2 ± 3.1, group B metformin‐CC: 29.6 ± 3.5 BMI (kg/m²): group A metformin‐letrozole: 30.0 ± 4.8, group B metformin‐CC: 30.2 ± 3.9 Duration of infertility (y): group A metformin‐letrozole: 3.8, group B metformin‐CC: 3.8 Country: Iran
Interventions	Group A: metformin 500 mg x 3/d for 6 ‐ 8 weeks. If pregnancy did not occur, 2.5 mg letrozole from cycle days 3‐7 was given orally. Group B: metformin 500 mg x 3/d for 6‐8 weeks. If pregnancy did not occur, 100 mg CC from cycle days 3‐7 was given orally. Treatment was continued for 2 cycles.
Outcomes	Endometrial thickness on day of hCG administration (cm), number of follicles > 18 mm in diameter, mean total estradiol level on day of hCG administration (pM/L), mean estradiol level by mature follicle (pM/L), regular menses after metformin, adverse effects of metformin, live birth rate, pregnancy rate, miscarriage rate
Notes	Ethical approval: yes, consent from the deputy of research and the medical ethics committee of Tehran University of Medical Sciences Informed consent: not obtained because quote: “it was the routine treatment protocol and it was just put in the frame of a structured study” (email with Dr Farnaz Sohrabvand) Source of funding: quote: "No funding was necessary" (email with Dr Farnaz Sohrabvand) Power calculation: not stated Authors were contacted about live birth, multiple pregnancies, OHSS, informed consent, funding. No data available on live birth, multiple pregnancies and OHSS. Information retrieved about informed consent and funding (email with Dr Farnaz Sohrabvand)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A series of blind envelopes numbered from 1 to 60 had been prepared. Each patient was invited to pull out an envelope and was placed by the clinic secretary in either the metformin‐letrozole group (number 1‐30) or in the metformin‐CC group (31‐60)."
Allocation concealment (selection bias)	Unclear risk	Quote: "A series of blind envelopes numbered from 1 to 60 had been prepared. Each patient was invited to pull out an envelope and was placed by the clinic secretary in either the metformin‐letrozole group (number 1‐30) or in the metformin‐CC group (31‐60)."
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants were not blinded.
Blinding of outcome assessment (detection bias) All outcomes	High risk	It is not plausible that outcome assessors were blinded if participants were not.
Incomplete outcome data (attrition bias) All outcomes	Low risk	One participant was excluded due to pregnancy after start of metformin treatment
Selective reporting (reporting bias)	Low risk	All outcomes were reported.
Other bias	Low risk	None