Fertility is known to decline significantly in women after the age of 35 years, and
fecundity is almost completely lost after the age of 45 . As age increases the natural
fecundity and pregnancy rates after assisted reproduction decrease .This reduction in
fecundity is thought to be due to ovarian aging mainly, which is defined as a decline in
both the quantity and quality of the ovarian follicle pool .The increase in patient's age
is associated with poor ovarian response, as represented by smaller ovarian volume, lower
antral follicle count and poor stromal vascularity. In addition to the reduction in
fecundity, there is an increase in spontaneous abortion rates in this group of women .It
has been reported that about 19% of all women undergo ART are 40 years, and they could be
considered as expected poor responders .Various protocols of ovarian stimulation have
been proposed to optimize IVF results in this age group, however, satisfactory results
remain a challenge . The lack of initial central down-regulation in early follicular
phase and adequate prevention of premature luteinizing hormone (LH) surge in late
follicular phase provide GnRH antagonist protocol as a potentially proper option .The use
of aromatase inhibitors in a GnRH antagonist protocol was suggested by some studies [Mit.
Yarali and colleagues demonstrated that adjuvant therapy with letrozole could improve the
response [Yarali et al., 2009]. Meanwhile, in another study, adding letrozole to ovarian
stimulation has no positive effect on the likelihood of pregnancy . Letrozole is a
selective, non-steroidal third generation aromatase inhibitor. Letrozole causes a
reduction in conversion of androstenedione and testosterone to estrone and estradiol by
inhibiting the aromatase enzyme activity . According to some published studies, the
decline in early follicular phase estrogen levels, and consequently decrease in negative
feedback of estrogen on FSH release in hypothalamic-pituitary axis cause an increase in
endogenous gonadotropin secretion and stimulation of ovarian follicular growth. In
addition, an increase in intraovarian androgens secondary to aromatase inhibition,
augments the follicular sensitivity to FSH stimulation and follicular growth . Letrozole
has no antiestrogenic effect over the endometrium . These reports prompted us to
hypothesize that use of letrozole as a co-treatment agent in GnRH antagonist protocol
might enhance cycle outcomes.
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