Tang 2006

Methods	Generation of allocation sequence: reported Allocation concealment method: reported Blinding method: yes Number and reasons for withdrawals: reported ITT analysis: yes Prospective, randomised, double‐blind, placebo‐controlled trial Metformin versus placebo
Participants	Diagnosis of PCOS followed the Rotterdam criteria (ESHRE/ASRM) 101 PCOS participants were randomised (52 in the metformin group and 49 in the placebo group) 5 cycles in the metformin group and 2 in the placebo group were abandoned due to poor response 47 cycles in each arm completed through to oocyte retrieval Age: 20 to 39 years Did not report the causes of infertility Both groups were matched for mean age, median duration of infertility, BMI, nulliparity, participants who had previous IVF cycle, ICSI cycles Inclusion criteria: a) serum testosterone concentration < 5.0 nmol/l b) normal prolactin concentration, thyroid, renal and haematological indices Exclusion criteria: a) concurrent hormone therapy within the previous 6 weeks b) any chronic disease that could interfere with the absorption, distribution, metabolism or excretion of metformin c) renal or liver disease d) systemic disease or diabetes (types 1 and 2)
Interventions	Metformin 850 mg bid from the first day of down‐regulation GnRH‐agonist to the day of oocyte retrieval Protocol for controlled ovarian hyperstimulation: long luteal phase pituitary down‐regulation using the GnRH analogue nafarelin 600 μg daily (Synarel®) with step up rec‐FSH (Puregon® starting dose of 100 IU). hCG (Profasi® 10000 IU) was administered when there were more than 3 follicles over 17 mm in diameter Oocyte retrieval was performed within 36 to 38 hrs after hCG injection All follicles with a diameter over 14 mm were aspirated and flushed twice with normal saline when oocytes were not found in the first aspirate Assisted reproductive technology (ART): IVF or ICSI (4 hours after oocyte retrieval) Embryo transfer: maximum of 2 embryos were transferred per participant on day 2 after follicle puncture under abdominal US guidance Catheter used for transfer: Wallace Luteal phase support: daily Cyclogest® pessary (400 mg) was used until the day of pregnancy test
Outcomes	Primary outcome: Fertilisation rate Secondary outcomes: a) number of days of gonadotrophins b) total dose of FSH given during stimulation c) number of follicles (> 14 mm) d) number of oocytes e) number of embryos transferred f) implantation rate g) pregnancy rate per woman h) clinical pregnancy rate per woman i) pregnancy rate per transfer j) clinical pregnancy rate per transfer k) live birth rate l) incidence of OHSS that required hospitalisation m) side effects n) fasting insulin o) fasting glucose p) SHBG q) free androgen index r) testosterone
Notes	Country of the study: United Kingdom
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 ‐ codes kept by a third party in the trial office
Blinding (performance bias and detection bias) All outcomes	Low risk	Double‐blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Reasons for withdrawals were reported. ITT analysis was performed
Selective reporting (reporting bias)	Low risk	All main outcomes were reported
Other bias	Low risk	Power calculation was performed. There were no significant differences in the baseline characteristics of the participants between the 2 groups