Clinical Question: Is metformin (Glucophage) more effective than clomiphene (Clomid) for improving fertility in nonobese women with polycystic ovary syndrome (PCOS)?

Setting: Outpatient (any)

Study Design: Randomized controlled trial (double-blinded)

Allocation: Concealed

Synopsis: Metformin and clomiphene have been used to increase fertility in women with PCOS. This is the first study to evaluate the medications head-to-head. One hundred women between 20 and 34 years of age with a body mass index lower than 30 kg per m² were randomly assigned (concealed allocation) to receive metformin 850 mg two times per day or clomiphene 150 mg three times per day. Each patient also received placebos of the opposite drug. Before starting the medications, the patients received a progesterone challenge, and medication was started on the third day of progesterone-induced menstruation. The main outcome, pregnancy rate, was assessed via intention to treat. Five patients receiving metformin and three receiving clomiphene dropped out and were not included in the analysis. At the end of six months of treatment, 31 patients (69 percent) taking metformin became pregnant compared with 16 (34 percent) taking clomiphene. If all the patients lost to follow-up in the clomiphene group became pregnant and none of those taking metformin did, the pregnancy rate would still be significantly higher with metformin. Three women would need to be treated with metformin instead of clomiphene for six months for one additional woman to become pregnant (95% confidence interval, 1.9 to 6.9). The rate of side effects was similar in each group (approximately 20 percent), and one patient in each group dropped out because of side effects.

Bottom Line: In nonobese women with PCOS, metformin is more effective than clomiphene for improving the rate of conception. (Level of Evidence: 1b)