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Am Fam Physician. 2023;108(2):203-204

Clinical Question

Is letrozole superior to clomiphene for infertility treatment among individuals with polycystic ovary syndrome (PCOS)?

Bottom Line

The meta-analysis of randomized controlled trials showed that for individuals with PCOS, treatment of infertility with letrozole compared with clomiphene resulted in a higher rate of ovulation induction, more pregnancies, and more live births. The conclusions are less than certain due to the high risk of bias in some studies. (Level of Evidence = 1a−)


The authors conducted a meta-analysis of randomized controlled trials (N = 29; 3,952 participants; 7,633 ovulation induction cycles) to compare the effect of letrozole and clomiphene on fertility among individuals with PCOS. They included studies that met the criteria of diagnosis of PCOS based on the 2003 Rotterdam criteria, had timed intercourse or insemination, and reported at least one of the three outcomes of interest. Seven studies were graded as having a high risk of bias to one or more of the following: quasi-randomization (n = 3), lack of fully described allocation concealment (n = 3), lack of masking (n = 6), or differences between groups in duration of infertility (n = 1). Meta-analysis for all primary outcomes favored letrozole: ovulation induction rate (22 studies; 6,862 participants; 67% vs. 59%; relative risk [RR] = 1.14; 95% CI, 1.06 to 1.21; P < .001), pregnancy rate (28 studies; 3,936 participants; 35% vs. 23%; RR = 1.48; 95% CI, 1.34 to 1.63; P < .001), and live birth rate (eight studies; 1,725 participants; 33% vs. 22%; RR = 1.49; 95% CI, 1.27 to 1.74; P < .001). The authors judged the certainty of evidence to be low for ovulation induction rate and moderate for pregnancy and live birth rate.

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POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see Copyright Wiley-Blackwell. Used with permission.

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