lETROZOLE

Where and how letrozole works?? Ans:  There is no direct effect of letrozole will  to improve follicle size and egg quality. Letroz will exert its effect only in cases where there is hyper activity of aromatase enzyme which is often a matter of speculation by physician but day 2 serum E 2 of > 80 pcg/ml is a strong evidence of favoring letrozole, adova  and all  other five aromatase inhibitors. Such drugs decrease the estrogen production in many sites including ovaries and breasts (That is why letrozole used in breast cancer). All (aromatase inhibitors) works at ovarian cortical level with varying degree of efficacy .The adverse effect on growing oocyte so as to cause cardiac or limb effects has been refuted by large studies.

Mode of action of Letrozole & other AI? Ans: Such drugs block the aromatase enzyme and thereby  cause blockage of conversion of androgens (C19) to oestrogens (C18). All AI decreases ovarian oestrogen biosynthesis but surprisingly favors estrogenic milleu  in the peripheral tissues (adipose tissues). If there is deficiency of aromatase enzymes, letrozole won’t work as Ovulation induction and letrozole has no direct  favorable effects on the granulosa cells which HMG exerts.

Dilemma on letrozole and answer is still unknown to infertility specialists :--If high estrogenic environment is congenial for granulosa cell proliferation and its function (remaining neutral to oocytes development)  then why PCO women who have at all poor oocytes quality either in stimulated cycles by CC, , ART where oestrogenic environment prevails all along . In fact all of us are searching where the shoe is pinching .  However, probabilities are

 A. High androgenic millieu à Poor functional competency of granulosa cell  and abnormally high androgen in liq.  Folliculi.

B. Gene pleomorphism in PCO à adverse effect on quality of granulosa cell function

C. Hyperinsulinemia in PCO