Lerzole its safety

Members opinion?? Letrozole does not increase the risk of adverse pregnancy or neonatal outcomes and major Rumor on Letrozole in causing congenital malformations at higher rate does not stand . congenital anomalies in patients conceived by ARTs.

Letrozole  is an oral non-steroidal aromatase inhibitor and initially  approved by US Food and Drug Administration ( FDA) for the adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer. Off-label it has been used for ovarian stimulation in assisted reproduction since 2001.

A recent retrospective cohort study published online November 7, 2016 in Journal of Human Reproduction concluded that “letrozole stimulation reduces the risk of miscarriage, with no increase in the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in women undergoing ART. Letrozole may thus be a safe option for mild ovarian stimulation.”

The study used data from Japanese national ART   registry between 2011 to 2013.  It included 3136 natural cycles and 792 letrozole-induced cycles with, fresh single embryo transfer resulting in clinical pregnancy were included in the analysis.The data was analyzed for rates of ectopic pregnancy, miscarriage and stillbirths as main pregnancy outcomes while preterm delivery, low birth weight, small/large for gestational age and major congenital anomalies were neonatal outcomes of primary importance.

After multivariate logistic regression, it was seen that women who received letrozole had 37% lower odds of miscarriage (P < 0.001). both groups were comparable for rates of congenital malformations. (natural cycle 1.5% vs letrozole 1.9%, P = 0.52). No difference in rates of congenital malformations seen when analyzed for in vitro fertilization or ICSI and early cleavage stage or blastocyst embryo transfer. 

Letrozole was associated with increased risks of birth defects and has been banned as ovulation induction in many countries including India since 2011, following reports of 2 studies citing increase incidences of congenital malformations (locomotor and cardiac abnormalities). One such study was presented at the  American Society ofReproductive Medicine 2005 Conference.  But, such off-label use of Letrozole for ovarian stimulation is not  illegal in USA and UK.It is still used  as an ovulation induction agent in ARTs.

However, The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial results presented at American Society for Reproductive Medicine (ASRM) 2013 clearly showed that as compared to clomiphene, ovulation rate, cumulative pregnancy rate and live birth rate is  better for letrozole in patients with PCOS, and it is not associated with increased risk of pregnancy loss, multiple pregnancies or adverse effects on fetus.[2]Subsequently, a review by Roque M et al affirmed the superiority of letrozole over clomiphene in PCOS patients. 

A 2014 Cochranedatabase systemic review also concluded “Letrozole improves live birth and pregnancy rates in subfertile women with anovulatory PCOS, compared to clomiphene citrate, though the evidence is low.”