Letrozole versus clomiphene for infertility in the polycystic ovary syndrome.
Level 2 - randomized trial
Multicenter, double-blind randomized controlled trial
PubMed 25006718 · doi:10.1056/NEJMoa1313517
What was done
A double-blind, multicenter randomized controlled trial enrolled 750 infertile women aged 18 to 40 with polycystic ovary syndrome (modified Rotterdam criteria), at least one patent fallopian tube, a normal uterine cavity, and a male partner with a sperm concentration of at least 14 million/mL. Participants were randomized 1:1 to receive either letrozole or clomiphene for up to five treatment cycles. The primary outcome was cumulative live birth during the treatment period.
What was found
Letrozole resulted in a significantly higher cumulative live-birth rate than clomiphene: 103 of 374 (27.5%) versus 72 of 376 (19.1%) (rate ratio 1.44; 95% CI, 1.10 to 1.87; P=0.007). Cumulative ovulation was also higher with letrozole (834 of 1352 cycles [61.7%] vs. 688 of 1425 cycles [48.3%], P<0.001). There were no statistically significant differences in pregnancy loss (31.8% vs. 29.1%), twin pregnancies (3.4% vs. 7.4%), or overall congenital anomalies (4 major anomalies with letrozole vs. 1 with clomiphene, P=0.65). Clomiphene caused more hot flushes, while letrozole was associated with more fatigue and dizziness.
Why it matters
This trial provides definitive evidence that letrozole is superior to clomiphene as a first-line treatment for achieving live births in women with PCOS-associated anovulatory infertility.
Limits
The study was restricted to five treatment cycles and excluded women over 40 or couples with concurrent severe male-factor or tubal infertility. The sample size was insufficient to definitively evaluate rare adverse safety outcomes or specific congenital anomaly risks.
Cited by
- supports With letrozole treatment, approximately 60 to 70 percent of PCOS patients ovulate, which is higher than the ovulation rate with Clomid (clomiphene).