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Letrozole more effective for pregnancy vs. clomiphene citrate in PCOS

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July 6, 2017

Women with polycystic ovary syndrome may experience higher rates of pregnancy and a shorter time to pregnancy when prescribed letrozole to induce ovulation compared with clomiphene citrate, according to study results.

Saad A. Amer, MD, FRCOG, clinical associate professor in the division of medical sciences and graduate entry medicine, School of Medicine at the University of Nottingham, Royal Derby Hospital Centre in the United Kingdom, and colleagues evaluated 159 subfertile women with PCOS between April 2007 and June 2014 randomly assigned 50 mg clomiphene citrate (Clomid, Sanofi Aventis; n = 79) or 2.25 mg letrozole (Femara, Novartis Pharmaceuticals; n = 80) per day to determine the effect of each drug on pregnancy rates.

Treatment began with one tablet per day of the assigned medication beginning on days 2 to 4 of a menstrual cycle or a progestogen-induced bleed for 5 days. If ovulation was not achieved with the first administration, the dose was doubled for the second cycle. Treatment continued for up to six ovulatory cycles or pregnancy. Nonresponders to treatment were crossed over to the other treatment after a 6-week break.

Overall, 149 participants (75 on letrozole) completed the first treatment; 79 conceived, and the remaining 76 (31 on letrozole) were switched to the second treatment.

Pregnancy rates were higher with letrozole compared with clomiphene citrate (43 vs. 30; P = .022). Among ovulating women, pregnancy rates were also higher with letrozole compared with clomiphene citrate (P = .024). Treatment with letrozole also resulted in higher pregnancy (P = .036) and ovulation (P = .045) rates compared with clomiphene citrate in the per cycle analysis.

Pregnancy and live-birth rates were not statistically different from participants who crossed over from letrozole to clomiphene citrate or those who crossed over from clomiphene citrate to letrozole.

Fewer cycles occurred before pregnancy with letrozole (median number of cycles, 4) compared with clomiphene citrate (median number of cycles, 6).
“This trial provides compelling evidence for the superiority of letrozole over clomiphene citrate as a primary [ovulation induction] agent in PCOS women with a 40% increase in pregnancy rates and with a shorter time to pregnancy,” the researchers wrote. “We, therefore, recommend that letrozole should replace [clomiphene citrate] as the first-line [ovulation induction] agent in PCOS. Further research is required to investigate possible mechanisms of the increased pregnancy rates with letrozole and of the cross-resistance between the two drugs.” – by Amber Cox

Disclosures: The researchers report no relevant financial disclosures.

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