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Previous Volume 356:551-566 February 8, 2007 Number 6 Next

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ABSTRACT

Background The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior.

Methods We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery.

Results The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combination-therapy group (P<0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). 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. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combination-therapy group (46.0%, P<0.001). 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.

Conclusions Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861 [ClinicalTrials.gov] .)

Source Information

From Pennsylvania State University College of Medicine, Hershey (R.S.L.); Duke University Medical Center, Durham, NC (H.X.B., E.R.M.); University of Colorado, Denver (W.D.S.); University of Texas Southwestern Medical Center, Dallas (B.R.C.); Wayne State University, Detroit (M.P.D.); Baylor College of Medicine, Houston (S.A.C.); University of Alabama, Birmingham (M.P.S.); University of Pennsylvania School of Medicine, Philadelphia (C.C.); University of Medicine and Dentistry of New Jersey, Newark (P.G.M.); Stanford University, Stanford, CA (N.A.C.); University of Pittsburgh, Pittsburgh (G.G.G.); Virginia Commonwealth University School of Medicine, Richmond (J.E.N.); University of California at San Francisco, San Francisco (L.C.G.); and the National Institute of Child Health and Human Development, Bethesda, MD (P.C.L.).

Address reprint requests to Dr. Legro at the Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, M.S. Hershey Medical Center, 500 University Dr., H103, Hershey, PA 17033, or at rsl1{at}psu.edu.

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