Renaissance of letrozole from anticancer drug to Ovulation inducing agents (more effective than CC Part 2

Are we lost ? No we are not:--A recent retrospective cohort study published online November 7, 2016 in Journal of Human Reproduction concluded that “letrozole stimulation reduces the 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. 

Renaissance of letrozole from anticancer drug to Ovulation inducing agents (more effective than CC !!:- Letrozole does not increase the risk of adverse pregnancy or neonatal outcomes and major congenital anomalies in patients conceived by ARTs. At Japan there was a RCT few years back in which study revealed that    births of ART babies from natural cycles IVF pregnancies were compared with Letrozole induced ART pregnancies.

  As on October, 2019: The Queen is back “The Board of Jury (FDA) unanimously declared that Queen is monogamous, with a very kind heat and deep sympathy to unfortunate subfertile who suffer from PCO. The Queen again was popular across the globe. 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 Cochrane  database 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.”  Long live the Queen!!

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1.         How to select cases who will be benefitted more by Letrozole than CC ??

I understand that etiology of anovulation in cases of all PCOS is not alike. Neither all anovulatory PCOS will response optimally to 4 common types of drugs (e.g., Clomiphene, letrozole group, Insulin sensitizers & Gonadotrophins). The altered cellular dynamics in intracellular & cell membrane receptors are principally falls in three to four major ways. Selecting the right oral OI agent for right women is, understandably a tough job and we commonly go as trial and error basis and thereby admitting some futile cycles. Such a “Hit or Miss attitude”, put a heavy task on Gynecologist specialist & Endocrinologist in particular & loss of morale of the concerned couple.-DR S K Pal, Kolkata drsrimantapal@gmail.com

Selecting the right ovulation INDUCIMG AGENT prior to initiation of class of Ov. Inducing agent??
A) Is there any clinical parameters / Laboratory parameter( be it Endocrine ,estimation of enzyme or Growth factor or any other parameter so as to which sub class of anovulatory PCOS will optimally respond without many futile cycles of OI. are best suited for CC and which will be mot benefited by Letrozole, Because mechanism is different. Further which PCOS need Insulin sensitizers or drugs to improve sensitivity can be judged before initiation  of ovulation induction  Ry?
Dr S K Pal,drsrimantapal@gmail.com