Higher endometrial receptivity caused by Letrozole in antagonist protocol-stimulated mouse uterus

ABSTRACT Background: The implantation rate of IVF remains low due to the adverse effect of ovarian stimulation on endometrial receptivity. Integrin ?3, E-cadherin and Leukemia Inhibitory Factor (LIF) are the best markers known for endometrial receptivity evaluation. In this study, the effect of adding Letrozole to antagonist protocol based on the expression of integrin ?3, E-cadherin and LIF level during implantation window was investigated. Letrozole is an inhibitor of aromatase that can prevent the supraphysiological estrogen level. The goal of the study was to prove that adding Letrozole to IVF antagonist protocol can increase the expression of Integrin ?3, E-cadherin, and LIF concentration of mice uterine. Methods: This is an experimental study with a post-test only group design using Balb/c mice mimicked ovarian stimulated IVF. Antagonist protocol was applied to one group as ovarian stimulation, while the other group received the combination of Letrozole and antagonist protocol. Uterus samples were collected 48 hours after ovarian stimulation. Integrin ?3 and E-cadherin expression were detected by immunohistochemistry technique and LIF level assay by ELISA. Normality test was carried out using Shapiro-Wilk, and homogeneity test by Levene’s T. Comparison between integrin ?3 and E-cadherin expression were tested by Mann-Whitney and Fisher’s exact, while comparison of LIF was tested by Mann- Whitney, with p<0.05 considered as significant. Path analysis was done to measure each variable contribution. Results: The Letrozole + GnRH antagonist treated mice showed significantly higher integrin ?3 (2.71 + 0.61 vs 1.04 + 0.08, p<0.05) and E-cadherin (3.73 + 0.28 vs 1.16 + 0.29, p<0.05) expression in endometrium. It also showed significantly higher level of uterine LIF (1.78 + 0.13 vs 1.66 + 0.17 ng/ml, p<0.05) during implantation window than GnRH antagonist treated mice alone. Expression of integrin ?3 (?2= 22.91, p<0.05) and E-cadherin (?2=36.00, p<0.05) were significantly higher in Letrozole group compared to control. Conclusion: Letrozole caused higher expression of Integrin ?3, e-cadherin, and, LIF concentration in Mice uterine stimulated by antagonist protocol. Letrozole had the highest contribution to the increase of E-cadherin. Integrin ?3 together with E-cadherin and Letrozole had 31.4% contribution to the increase of LIF. Keyword: Letrozole, antagonist protocol, integrin ?3, E-cadherin, LIF