Context: Clomiphene citrate (CC) and metformin are two effective drugs used to induce ovulation in patients with polycystic ovary syndrome (PCOS), even if it is still unclear which compound between them should be initially administered.

Objective: To compare in a clinical setting the efficacy of CC and metformin as first-line approaches for treating anovulation in infertile PCOS patients.

Design: Multicenter non-randomized prospective controlled study.

Setting: Departments of Obstetrics & Gynecology, Universities "Magna Graecia" of Catanzaro and "Federico II" of Naples, Italy.

Patients: Eighty infertile anovulatory patients with PCOS allocated in two body mass index (BMI)- and age-matched groups (experimental and control groups).

Interventions: Six months of 1700 mg/day metformin treatment (experimental group) or CC administered using a traditional incremental-doses protocol (control group). In both groups, patients who ovulated under treatment continued the therapy for a total of six months.

Main Outcome Measures: Reproductive outcomes.

Results: Experimental and control groups were studied for a total of 204 and 169 cycles, respectively. No difference between two groups was observed in ovulation (55.4% vs. 59.8%, respectively; P=0.396), pregnancy (10.8% vs. 11.2%, respectively; P=0.888), and abortion (55.4% vs. 59.8%, respectively; P=0.396) rates. The cumulative pregnancy rate was not different between groups (62.9% vs. 48.6%, respectively; P=0.225).

Conclusion: Both a six-course of 1700 mg/day metformin treatment and CC administrated in an escalation-protocol are two effective first-line approaches for improving fertility in anovulatory PCOS women.