Qptimizing The Best Time Of Endometrial Receptivity In Hormone Replacement Therapy Frozen-Thawed Embryo Transfer Cycles

Objective:Endometrial receptivity represents a crucial limit for the success of in vitro fertilization and frozen-thawed embryo transfer (IVF-FET) treatments. Implantation failure is a major factor limiting the success of IVF. The lack of synchrony between the embryo development and endometrial maturation results in an implantation failure. Frozen-thawed embryo transfer in hormone therapy(HRT) cycles has a number of advantages. Medical staff or patients can select the date of embryo thawing and transfer, minimizing the fear and anxiety of cycle cancellation, and the centers are able to organize their staffing and laboratory workload accordingly. What’s more, in the process of endometrial preparation cycle, it is convenient, effective and safe for using hormone replacement (HRT) cycles. So we detected the development of the pinopodes and the expression of integrinαvβ3, HOXA10and LIF to assess endometrial receptivity before frozen-thawed embryo transfer (FET) in HRT cycles. This could help in optimizing the endometrial preparation and the timing of embryo transfer for better embryo-endometrial synchronization.Methods:46women with tubal-factor or male-factor infertility were recruited. Exogenous oestradiol was administrated orally from the day3of their cycles and progesterone was started intramuscularly from the day16. They were divided into five groups (P3, P4, P5, P6, P7) depending on the duration of exposure to progesterone:3,4,5,6,7days, and endometrial biopsies were operated on the second day after each group had been finished Progesterone injection respectively. Pinopodes morphology and coverage were assessed by scanning electron microscopy (SEM) and western blot (WB) was performed to evaluate the protein expression of integrin αvβ3, HOXA10and LIF.Results:(I) Pinopodes morphology:The developmental stages of pinopodes were morphologically classified as developing, fully developed and regressing. In our experiment, SEM found that55%(6/11) patients’ endometrial present the state of developing pinopodes in group P5; Fully developed pinopodes mainly appeared in group P6, and the proportion was69%(9/13); Regressing pinopodes were recognized on groups P7(70%,7/10). According to the development of pinopodes, the receptivity of endometrium were better in group P6than other groups.(II) Pinopodes coverage: The coverage of pinopodes were extremely low in P3and P4group, and other three groups (P5, P6and P7)were significantly higher than P3and P4group respectively (P<0001); The coverage of pinopodes of the endometrial surface were the highest in P6group. Which indicated that, in P6group, the receptivity of endometrium was better than other groups.(Ⅲ) molecular markers:The protein of integrin αvβ3, HOXA10and LIF had no difference in P3vs. P4groups, but have profound statistically difference in P3vs. P6groups, P5vs. P6groups and P6vs. P7groups. The protein of these three markers showed the peak levels in P6group, which suggested that the receptivity of endometrium in P6group may be the best.Conclusions:in our HRT cycles, The maximum receptivity of endometrium was on day P6in most patients, which most possibly suitable for implantation. According to the situation of development of day3frozen embryos in vitro, the optimal timing for transfer may be on day3after progesterone administration in HRT cycles. In other words, transferring day3embryos to day P3endometrium may achieve better synchronization.