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

• Published in: The New England journal of medicine Vol. 356; no. 6; pp. 551 - 566
• Main Authors: Legro, Richard S, Barnhart, Huiman X, Schlaff, William D, Carr, Bruce R, Diamond, Michael P, Carson, Sandra A, Steinkampf, Michael P, Coutifaris, Christos, McGovern, Peter G, Cataldo, Nicholas A, Gosman, Gabriella G, Nestler, John E, Giudice, Linda C, Leppert, Phyllis C, Myers, Evan R
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 08.02.2007
• Subjects: Adult; Biological and medical sciences; Birth control; Birth Rate; Blister packs; Clomiphene - adverse effects; Clomiphene - therapeutic use; Drug dosages; Drug Therapy, Combination; Female; Fertility Agents, Female - adverse effects; Fertility Agents, Female - therapeutic use; General aspects; Gynecology. Andrology. Obstetrics; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Infertility; Infertility, Female - drug therapy; Infertility, Female - etiology; Kaplan-Meier Estimate; Live Birth; Medical sciences; Metformin - adverse effects; Metformin - therapeutic use; Ovulation Induction - methods; Patient Compliance; Polycystic ovary syndrome; Polycystic Ovary Syndrome - complications; Polycystic Ovary Syndrome - drug therapy; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Reproductive health; Statistical methods; Sterility. Assisted procreation; Thyroid diseases; Women; Non steroidal estrogen; Ovulation inducer; Female sterility; Clomifene; Polycystic ovary; Female genital diseases; Medicine; Ovarian diseases; Hypoglycemic agent; Biguanides; Cyst; Benign neoplasm; Metformin
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa063971

This multicenter, randomized trial compared the effects of clomiphene citrate plus placebo, metformin plus placebo, and combination therapy in infertile women with the polycystic ovary syndrome. The rate of live birth was significantly higher with clomiphene than with metformin; there was no significant difference between the rates with combination therapy and with clomiphene alone. Multiple birth was a complication associated with clomiphene but was infrequent. These data support the use of clomiphene over metformin for the treatment of infertility in women with the polycystic ovary syndrome. In infertile women with the polycystic ovary syndrome, the rate of live birth was significantly higher with clomiphene than with metformin. The polycystic ovary syndrome affects 7 to 8% of women 1 and may be the most common cause of female infertility. 2 Anovulation, 2 early pregnancy loss, 3 and later pregnancy complications 4 have all been implicated in the low fecundity of women with this disorder. Obesity is also common in such women, 5 and this condition alone appears to have an adverse effect on reproduction. 6 , 7 The cause of the polycystic ovary syndrome is poorly understood, and both the diagnosis and treatment of the disorder are controversial. 5 , 8 , 9 Women with this syndrome have hyperandrogenism, 10 morphologic changes in the ovary (polycystic), 10 inappropriate gonadotropin secretion (elevated . . .