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Treating Infertility Caused by Polycystic Ovary Syndrome

Clomiphene remains the drug of choice.

Polycystic ovary syndrome (PCOS), characterized by hyperandrogenemia and oligomenorrhea and associated with the metabolic syndrome and insulin resistance, is a common cause of infertility. Insulin sensitizers constitute one recommended treatment; metformin has been reported to increase ovulation rates in obese, infertile women with PCOS, but clomiphene citrate is more commonly used to induce ovulation.

In this trial, investigators with the NIH’s Reproductive Medicine Network randomized 626 infertile women with PCOS to receive extended-release metformin, clomiphene citrate, or a combination of both therapies; live birth was the primary outcome. Participants (average body-mass index, about 35) were treated for up to 6 months, with therapy discontinued after a positive pregnancy test. The rate of live birth was significantly lower in the metformin group (7.2%) than in either the clomiphene group (22.5%) or the combination therapy group (26.8%). Combination therapy increased the ovulation rate over clomiphene alone but did not result in a significant increase in the live birth rate. Regardless of therapy, women with a BMI below 30 had a significantly higher birth rate than heavier women. Serious adverse events, generally related to pregnancy, were more common with clomiphene, and discontinuation was more common with metformin.

Comment: These results do not negate the use of insulin sensitizers for general treatment of women with PCOS. However, the findings, which contradict those of earlier meta-analyses and reports, indicate that treatment of infertility in women with PCOS is best accomplished initially by the use of clomiphene citrate.

— Robert W. Rebar, MD

Published in Journal Watch General Medicine February 7, 2007

Citation(s):

Legro RS et al. Clomiphene, metformin, or both versus metformin for infertility in the polycystic ovary syndrome. N Engl J Med 2007 Feb 8; 356:551-66.

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Guzick DS. Treating the polycystic ovary syndrome the old-fashioned way. N Engl J Med 2007 Feb 8; 356:622-4.

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• Medline abstract (Free)