Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome

Richard S. Legro, Huiman X. Barnhart, William D. Schlaff, Bruce R. Carr, Michael P. Diamond, Sandra A. Carson, Michael P. Steinkampf, Christos Coutifaris, Peter G. McGovern, Nicholas A. Cataldo, Gabriella G. Gosman, John E. Nestler, Linda C. Giudice, Phyllis C. Leppert, Evan R. Myers

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)551-566
Number of pages16
JournalNew England Journal of Medicine
Volume356
Issue number6
DOIs
StatePublished - Feb 8 2007

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Clomiphene
Polycystic Ovary Syndrome
Metformin
Infertility
Group Psychotherapy
Live Birth
Placebos
Multiple Birth Offspring
Multiple Pregnancy
Pregnancy Complications
Birth Rate
Pregnancy Rate
First Pregnancy Trimester
Ovulation
Insulin
Pregnancy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Legro, R. S., Barnhart, H. X., Schlaff, W. D., Carr, B. R., Diamond, M. P., Carson, S. A., ... Myers, E. R. (2007). Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. New England Journal of Medicine, 356(6), 551-566. https://doi.org/10.1056/NEJMoa063971

Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. / 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.

In: New England Journal of Medicine, Vol. 356, No. 6, 08.02.2007, p. 551-566.

Research output: Contribution to journalArticle

Legro, RS, Barnhart, HX, Schlaff, WD, Carr, BR, Diamond, MP, Carson, SA, Steinkampf, MP, Coutifaris, C, McGovern, PG, Cataldo, NA, Gosman, GG, Nestler, JE, Giudice, LC, Leppert, PC & Myers, ER 2007, 'Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome', New England Journal of Medicine, vol. 356, no. 6, pp. 551-566. https://doi.org/10.1056/NEJMoa063971
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. / Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. In: New England Journal of Medicine. 2007 ; Vol. 356, No. 6. pp. 551-566.
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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.",
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AU - Legro, Richard S.

AU - Barnhart, Huiman X.

AU - Schlaff, William D.

AU - Carr, Bruce R.

AU - Diamond, Michael P.

AU - Carson, Sandra A.

AU - Steinkampf, Michael P.

AU - Coutifaris, Christos

AU - McGovern, Peter G.

AU - Cataldo, Nicholas A.

AU - Gosman, Gabriella G.

AU - Nestler, John E.

AU - Giudice, Linda C.

AU - Leppert, Phyllis C.

AU - Myers, Evan R.

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N2 - 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.

AB - 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.

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