First-line letrozole may be a better alternative to clomiphene citrate for PCOS
The primary endpoint of pregnancy rate was significantly higher in women who received letrozole than those treated with CC at the first-line setting (61.2 percent vs 43 percent; p=0.022 for intent-to-treat analysis and 62.7 percent vs 43.2 percent; p=0.018 for per-protocol analysis). [Human Reproduction 2017;doi:10.1093/humrep/dex227]
The pregnancy rate per ovulating patient was significantly higher in women who had letrozole than CC (70.1 percent vs 50.8 percent; p=0.024). Similarly, ovulation rate per cycle was also higher with letrozole (75 percent vs 67 percent; p=0.045) compared with CC.
Compared with CC users, a significant shorter length of time-to-pregnancy was observed among letrozole users (six vs four treatment cycles).
“This trial provides compelling evidence for the superiority of letrozole over CC as a primary [ovulation induction (OI)] agent in PCOS women with a 40 percent increase in pregnancy rates and with a shorter time-to-pregnancy,” said the researchers.
In addition, although the live birth (LB) rates were not significantly different between the treatment arms, there was a noticeable trend towards higher LB rates in the letrozole treatment arm than in the CC arm (48.8 percent vs 35.4 percent; p=0.089).
According to the researchers, CC has been known as the standard first-line treatment in women with PCOS, but recently letrozole was considered as a better treatment option.
“We, therefore, recommend that letrozole should replace CC as the first line OI agent in [women with] PCOS,” said the researchers.
This single-centre, double-blind randomized controlled trial consisted of 159 subfertile women with PCOS (mean age 28 years, median body mass index 27 kg/m2). Participants were randomized in a 1:1 ratio to letrozole 2.5 mg (n=80) or CC 50 mg (n=79) once daily as the starting dose, which was doubled on the second cycle if ovulation was not attained. Treatment was continued until pregnancy or up to six ovulatory cycles.
The findings were consistent with a previous study showing higher pregnancy and LB rates in women treated with letrozole compared with CC. However, the authors cautioned that their reported findings and quality of evidence were deemed low. [Cochrane Database Syst Rev 2014;2:CD010287]
The results showed that the safety profile of letrozole was also consistent with several previous studies, which demonstrated no increase in foetal or neonatal anomalies in the letrozole pregnancies, noted the researchers. [Fertil Steril 2006;85:1761-1765; N Engl J Med 2014;371:119-129]“Further research is required to investigate possible mechanisms of the increased pregnancy rates with letrozole and of the cross-resistance between the two drugs,” they added.