For women with polycystic ovary syndrome (PCOS), the fertility drug clomiphene is superior to metformin in achieving a live birth, a recent head-to-head study has reported.
A multicenter randomised trial showed that the live-birthrate among women given clomiphene was three times the rate of those treated with metformin, Dr Richard Legro, of Pennsylvania State University, and colleagues, reported in the 8 February issue of the New England Journal of Medicine.
Multiple births were a minor complication, occurring among the women given clomiphene but not among those treated with metformin, they said.
Clomiphene is an antiestrogenic agent that promotes the release of follicle-stimulating hormone, stimulating the development of ovarian follicles and ovulation. Researchers have hoped that metformin, an insulin sensitiser used to treat diabetes, might help overcome infertility in polycystic ovary syndrome.
The researchers randomly assigned 626 infertile women with polycystic ovary syndrome to receive clomiphene plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to six months. Medication was discontinued when pregnancy was confirmed, and the participants were followed until delivery.
The live-birth rate was 22.5% (47 of 209) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group. The difference in the number of births between the clomiphene only group and the combined clomiphene-metformin group was not statistically significant, the researchers said.
Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group.
Clomiphene is known to stimulate the release of more than one egg at a time. However, the rate of multiple pregnancy seen in the study for women treated with clomiphene was less than the multiple pregnancy rate seen following in vitro fertilization, the authors wrote.
With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group, the researchers added.
In summary, Dr. Legro’s team wrote, “our study supports the use of clomiphene citrate alone as first-line therapy for infertility in women with polycystic ovary syndrome.
“We did not find a significant benefit of combination therapy with clomiphene and metformin over clomiphene alone with respect to the live-birth rate. In addition, the results of our study underscore the limitations of the use of ovulation as a surrogate marker for live birth in infertility trials,” they concluded.
Follow us on
