Comparison of clomiphene citrate, metformin, or the combination of both for first-line ovulation induction and achievement of pregnancy in 154 women with polycystic ovary syndrome.

Objective: To determine which first-line medication is more effective in polycystic ovary syndrome (PCOS) patients for ovulation induction and pregnancy achievement and to verify whether any patient characteristic is associated with a better response to therapy.
Design: Observational comparative study.
Setting: Fertility clinic.
Patient(s): One hundred fifty-four infertile women with oligomenorrhea and hyperandrogenism.
Intervention(s): Group 1 (56 patients) received clomiphene citrate (CC) 50 mg from days 5-9 of the cycle. Group 2 (57 patients) received 500 mg of metformin 3 times a day. Group 3 (41 patients) received both medications.
Main Outcome Measure(s): Ovulation and pregnancy.
Result(s): Patients receiving metformin alone had an increased ovulation rate compared with those receiving CC alone (75.4% vs. 50%). Patients on metformin had similar ovulation rates compared with those in the combination group (75.4% vs. 63.4%). Pregnancy rates were equivalent in the 3 groups. Response to metformin was independent of body weight and dose. Finally, nonsmoking predicted better ovulatory response overall as well as lower fasting glucose for CC and lower androgens for metformin.
Conclusion(s): Metformin is better for ovulation induction than CC alone and equivalent for pregnancy achievement. We suggest that metformin can be used first for ovulation induction in patients with PCOS regardless of their weight and insulin levels because of its efficacy and known safety profile.