Endometrial receptivity markers in infertile women stimulated with letrozole compared with clomiphene citrate and natural cycles

Abstract

Though various advantages associated with the use of letrozole as an ovulation inducing drug are documented, there is inadequate information regarding its effect on endometrial receptivity. Expression of endometrial receptivity markers including a v b 3 integrin, L-selectin, LIF, and pinopods during the implantation window in infertile women stimulated with letrozole or clomiphene citrate (CC), and spontaneous cycles is investigated. A total of 36 women were included in the study out of which 16 women were diagnosed with primary unexplained infertility and the other 20 women with severe oligoasthenozoospermic/azoospermic male partners. Both groups were sub-divided into three groups; women stimulated with letrozole, or with CC, and the third group was allowed to ovulate spontaneously (natural cycles). Women having natural cycles and not given any drug were considered as controls. Once ovulation was confirmed by ultrasonography, endometrial samples were collected on the seventh day post-ovulation and analyzed. In women with unexplained infertility treated with letrozole and CC, epithelial and stromal expression of a v b 3 integrin, L-selectin, leukemia inhibitory factor (LIF), and pinopod formation was found to be significantly higher as compared to controls. Expression of these receptivity markers was found to be comparable amongst the letrozole, CC, and control groups in women with severe oligoasthenozoospermic/azoospermic male partners. Cell cycle analysis showed similar cell cycle phase fractions on comparing the CC and the letrozole groups. Stimulation with letrozole and CC appears to enhance endometrial receptivity in women with unexplained infertility. However, letrozole and CC did not have any significant effect on the endometrial receptivity markers of women with severe oligoasthenozoospermic/azoospermic male partners.

The effect of letrozole versus artificial hormonal endometrial preparation on pregnancy outcome after frozen-thawed embryos transfer cycles: a randomized clinical trial

“…In this way, Miller et al concluded that the lack of endometrial αvβ3 integrin expression is associated with a poor prognosis outcome in IVF cycles that might be improved with letrozole co-treatment [22]. Elsewhere, Ganesh et al, in a preliminary study reported that OS with the use of letrozole was associated with a significant increase in the epithelial and stromal expression of uterine receptivity markers, including integrin, leukaemia inhibitory factor, and L-selectin, in women with unexplained infertility compared with natural cycles [23]; all of which may have positive effects on the pregnancy rate after ET [2]. Meanwhile, we observed a slight increase in the endometrial thickness on the day of ET in the letrozoletreated group.…”

Pregnancy Outcomes Following Letrozole Use in Frozen-thawed Embryo Transfer Cycles: A Systematic Review and Meta-analysis

“…Cortinez et al observed similar EMT rates and endometrial morphology in a group receiving letrozole treatment compared to NC [13]. Furthermore, Ganesh et al reported that letrozole induces higher expression of integrin in the endometrial epithelium than NC, which improves the endometrial environment [14]. The superiority of letrozole could also be due to activation of the Wnt/B-catenin pathway [36,37].…”

“…Numerous researchers have investigated the characteristics of letrozole for induction of ovulation. Letrozole has been proved to promote the endometrial thickness required for embryo implantation and does not impair endometrial receptivity [13,14]. Moreover, unlike CC, it has no anti-oestrogenic effects on the endometrium and cervical mucus [15].…”

<p>Pregnancy And Neonatal Outcomes Of hMG Stimulation With Or Without Letrozole In Endometrial Preparation For Frozen–Thawed Embryo Transfer In Ovulatory Women: A Large Retrospective Cohort Study</p>

“…Letrozole improves the outcome of FET probably by increasing the expression of receptivity marker, integrin, among ART patients with low integrin expression. Ganesh et al demonstrated that the use of letrozole is associated with significantly increased expression of integrin in the uterine endometrium, compared with natural cycles in patients with unexplained infertility 17. Furthermore, Miller et al also reported that letrozole upregulates the expression levels of integrin and significantly increases the pregnancy and implantation rates after IVF among women who lacked normal expression levels of integrin 18.…”