Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.
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].).
Legro
Richard S
RS
Department of Obstetrics and Gynecology, Pennsylvania State University College of Medicine, M.S. Hershey Medical Center, Hershey, PA 17033, USA. rsl1@psu.edu
Barnhart
Huiman X
HX
Schlaff
William D
WD
Carr
Bruce R
BR
Diamond
Michael P
MP
Carson
Sandra A
SA
Steinkampf
Michael P
MP
Coutifaris
Christos
C
McGovern
Peter G
PG
Cataldo
Nicholas A
NA
Gosman
Gabriella G
GG
Nestler
John E
JE
Giudice
Linda C
LC
Leppert
Phyllis C
PC
Myers
Evan R
ER
D000328:Adult; D001723:Birth Rate; D002996:Clomiphene / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005300:Fertility Agents, Female / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007247:Infertility, Female / Q000188:drug therapy* / Q000209:etiology; D053208:Kaplan-Meier Estimate; D050498:Live Birth; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D010062:Ovulation Induction / Q000379:methods; D010349:Patient Compliance; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000188:drug therapy*; D011247:Pregnancy; D011248:Pregnancy Complications; D011272:Pregnancy, Multiple
D005300:Fertility Agents, Female; D007004:Hypoglycemic Agents; D002996:Clomiphene; D008687:Metformin