Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome

Authors

Richard S. Legro, Pennsylvania State University College of MedicineFollow
Huiman X. Barnhart, Duke University Medical Center
William D. Schlaff, University of Colorado at Denver
Bruce R. Carr, University of Texas Southwestern Medical Center at Dallas
Michael P. Diamond, Wayne State University
Sandra A. Carson, Baylor College of Medicine
Michael P. Steinkampf, University of Alabama - Birmingham
Christos Coutifaris, University of Pennsylvania School of Medicine
Peter G. McGovern, University of Medicine and Dentistry of New Jersey
Nicholas A. Cataldo, Stanford University
Gabriella G. Gosman, University of Pittsburgh - Main Campus
John E. Nestler, Virginia Commonwealth University, Medical College of VirginiaFollow
Linda C. Guidice, University of California - San Francisco
Phyllis C. Leppert, National Institute of Child Health and Human Development
Evan R. Myers M.P.H., Cooperative Multicenter Reproductive Medicine Network, Duke University Medical Center

Document Type

Article

Original Publication Date

2007

Journal/Book/Conference Title

The New England Journal of Medicine

Volume

356

Issue

6

First Page

551

Last Page

566

DOI of Original Publication

10.1056/NEJMoa063971

Comments

Originally published at http://dx.doi.org/10.1056/NEJMoa063971

Date of Submission

January 2015

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 combinationtherapy 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 combinationtherapy 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.)

Rights

From The New England Journal of Medicine, Legro, R. S., Barnhart, H. X., et al., Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome, Vol. 356, Page 551, Copyright © 2007 Massachusetts Medical Society. Reprinted with permission.

Is Part Of

VCU Obstetrics and Gynecology Publications