Palomba 2004.

Methods	RCT Setting: Italy Method of randomisation: computer‐generated random allocation sequence in double block Blinding: double Number randomised: 120
Participants	Summary: diagnostic laparoscopy and metformin vs LOD and multivitamins Inclusion criteria: PCOS (NIH criteria), CC resistance (failure to ovulate during total of 3 consecutive cycles using CC 150 mg/d for 5 days from day 3‐7), overweight (BMI 25‐30) Exclusion criteria: age < 22 years or > 34 years, hypothyroidism, hyperprolactinaemia, Cushing's syndrome, nonclassical congenital adrenal hyperplasia, current or previous (within 6 months) use of oral contraceptives, glucocorticoids, antiandrogens, ovulation induction agents, antidiabetic or antiobesity drugs, other hormonal drugs. Comorbid conditions including neoplastic, metabolic, hepatic and cardiovascular disease. Diabetes, renal disease, malabsorptive disorders. Glucose intolerance, special diet or physical activity programme. Organic pelvic disease, previous pelvis surgery, suspected peritoneal factor infertility, tubal or male factor infertility. Smokers. Alcohol Baseline characteristics of each group: metformin (n = 60) vs LOD (n = 60) Mean age (SD) 26.8 (2.2) vs 27.5 (2.4) Mean BMI (SD) 28.1 (1.7) vs 27.6 (1.6) Mean fasting blood sugar, mg/dL (SD) 98.3 (8.9) vs 95.9 (7.8) Mean fasting insulin, micU/mL (SD) 18.8 (5.5) vs 20.8 (5.7) Mean testosterone, ng/mL (SD) 0.8 (0.1) vs 0.9 (0.1 Dropouts: 11
Interventions	Main intervention: metformin 850 mg twice daily; LOD (3‐6 punctures per ovary, each for 2‐3 seconds with insulated needle adjusted at 40 watts, ovaries then washed with crystalloid solution, injured areas covered with hyaluronic acid gel) Duration: 6 months then CC added 150 mg/d from day 3‐6 Co‐interventions: diagnostic laparoscopy (group 1); multivitamins 2 tablets/d (group 2)
Outcomes	Primary: live birth rate, gastrointestinal side effects Secondary: clinical pregnancy, menstrual frequency, ovulation: follicle tracking on US, miscarriage
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer random‐number generator
Allocation concealment (selection bias)	Unclear risk	Allocation sequence concealed until the interventions were assigned
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants were blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Investigators were blinded
Incomplete outcome data (attrition bias) All outcomes	High risk	Dropouts stated with reasoning. 6 women in the diagnostic laparoscopy and metformin group, 5 women in the LOD group. Not an ITT analysis because dropouts were excluded from analysis
Selective reporting (reporting bias)	Low risk	All outcomes clearly reported
Other bias	Low risk	No evidence of other bias