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| Letrozole Tablets |
Letrozole
is an oral non-steroidal aromatase inhibitor 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. [1] 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. [3]
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.” [4]
[1] Biljan MM, Hemmings R, Brassard N, et al. The outcome of 150 babies
following treatment with letrozole or letrozole and gonadotropins. Presented at
the American Society for Reproductive Medicine 61st Annual Meeting; October
14-19, 2005; Montreal, Quebec. Abstract O-231.
[2] https://www.ncbi.nlm.nih.gov/pubmed/22265923
[3] https://www.ncbi.nlm.nih.gov/pubmed/26479460
[4] https://www.ncbi.nlm.nih.gov/pubmed/24563180
