Clomiphene: old-fashioned but effective

It may be time to return to the old-fashioned standard when it comes to treating infertility in women with polycystic ovary syndrome. A recent multicenter, randomized trial involving 626 women finds that clomiphene citrate is three times better than metformin at achieving a live birth in infertile women with the condition, but that it's also about six times more likely to produce a multiple birth.

Researchers calculated a live-birth rate of 22.5% for a group of women taking clomiphene citrate plus placebo, 7.2% for a group taking extended-release metformin plus placebo, and 26.8% for a group of women taking a combination of the two active agents. The rates of multiple pregnancy for the three groups, respectively, were 6.0%, 0%, and 3.1%, while the rates of conception for the three groups were 39.5%, 21.7%, and 46%, respectively. Rates of first-trimester pregnancy loss and adverse events did not differ significantly between the three groups, although gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms were less frequent, in the metformin group than in the clomiphene group.

The author of an accompanying editorial points out that the results of this latest study indicate that the combination of clomiphene and metformin provides no greater benefit than clomiphene alone because while the ovulation rate was higher in the combination group, it did not translate into a higher live-birth rate.

Legro RS, Barnhart HX, Schlaff WD, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med. 2007;356:551-566.

Guzick DS. Treating the polycystic ovary syndrome the old-fashioned way. N Engl J Med. 2007;356:622-624.