探索激素替代冻融胚胎移植周期最佳的子宫内膜容受时间

发布时间：2018-03-08 13:23

本文选题：胞饮突　切入点：黄体酮　出处：《浙江大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的：在体外受精-冻融胚胎移植(IVF-FET)过程中,子宫内膜容受性起着至关重要的作用,种植失败仍然是IVF治疗中主要的限制性因素。胚胎与子宫内膜的发育不同步是导致种植失败的主要原因。FET周期有很多优点,医护人员和病人可以选择胚胎解冻和移植的时间,减少并发症,提高累积妊娠率等。在子宫内膜准备周期方案中,激素替代治疗(HRT)相对来说方便、有效、安全,因此本课题为了评估激素替代-冻融胚胎移植(HRT-FET)周期的子宫内膜容受性,检测了子宫内膜的形态学标志物胞饮突,及与子宫内膜容受性相关的其他分子标志物,包括整合素ανβ3、同源框基因A10(HOXA10)蛋白和白血病抑制因子(LIF)的表达。方法：选择在我院即将行HRT-FET周期的46例不孕女性,根据子宫内膜暴露于P连续使用的天数(3,4,5,6,7天)的不同分为5组,分别记为P3,P4,P5,P6,P7组,各组均在用完黄体酮的第二天取内膜。应用扫描电子显微镜(SEM)和蛋白免疫印迹(WB)方法分别评估子宫内膜胞饮突的形态和覆盖面积,及整合素αvβ3、HOXA10、LIF蛋白的表达。结果：(Ⅰ)根据胞饮突发育的阶段,我们将胞饮突分为：发育中、发育完全和衰退期三个阶段。在HRT-FET患者中,SEM发现：发育中的胞饮突大部分出现在P5组中,患者子宫内膜呈发育中的胞饮突状态所占比例为55%(6/11)；发育完全的胞饮突主要出现在P6组中,患者子宫内膜呈发育完全的胞饮突状态所占比例为69%(9/13)；而衰退期的胞饮突主要出现在P7组中,患者子宫内膜呈衰退期的胞饮突状态所占比例为70%(7/10)。胞饮突发育提示,P6组患者子宫内膜容受性的好于其他组。(Ⅱ)胞饮突的覆盖面积：在P3和P4组中胞饮突的覆盖面积非常低；P5,P6,和P7这三组都分别高于P3和P4组(P.0001)；在P6组中,胞饮突的覆盖面积均高于P5和P7组(P.0001)；胞饮突覆盖面提示,P6组患者子宫内膜容受性好于其他组。(Ⅲ)分子标志物：整合素avβ3, HOXA10与LIF蛋白的表达在P3vs.P4组中没有差异,但是在P3vs.P6组,P5vs.P6组和P6vs.P7组比较中,P6组中整合素avβ3, HOXA10和LIF蛋白的表达最高,结果均有统计学差异；分子标志物的表达提示,P6组患者的子宫内膜容受性最佳。结论：在本实验中心所实施的HRT方案中,大部分人黄体酮补充6天的子宫内膜容受性最佳,这个时间可能最适合胚胎种植。根据第3天的冻融胚胎的发育情况,将第3天的胚胎移植到黄体酮补充了3天的子宫内,可能会更好的实现同步化。
[Abstract]:Objective: endometrial receptivity plays an important role in IVF-FETs during in vitro fertilization and frozen-thawed embryo transfer. Implantation failure is still a major limiting factor in the treatment of IVF. The synchronization of embryo and endometrium is the main reason for the failure of implantation. There are many advantages in the cycle of implantation. Health care workers and patients can choose the time of embryo thawing and transfer. In endometrial preparation cycle, hormone replacement therapy (HRT) is relatively convenient, effective and safe. Therefore, in order to evaluate the endometrial receptivity of HRT-FETs, a morphological marker of endometrium and other molecular markers related to endometrial receptivity, were detected. These include the expression of integrin 伪谓尾 3, homobox gene A10, HOXA10, and leukemia suppressor LIFs. Methods: 46 infertile women who were about to undergo HRT-FET cycle in our hospital were divided into 5 groups according to the days of continuous use of endometrium exposed to P). The endometrium of each group was collected on the second day after using progesterone. The morphology and coverage area of the endometrium and the expression of integrin 伪 v 尾 3HOXA10 LIF protein were evaluated by scanning electron microscopy (SEM) and Western blot (WB). Results (I) according to the stage of development, we divided the process into three stages: development, complete development and decline. In HRT-FET patients, it was found that most of the developing processes occurred in P5 group. The proportion of the endometrium of the patients with developing process was 55 / 11. The fully developed process mainly appeared in the P6 group, and the rate of the development of the endometrium in the P6 group was higher than that in the control group (P _ (6)). The percentage of the patients with fully developed cellular processes in the endometrium was 69 / 9 / 13, while the recessionary processes were mainly present in the P7 group. The percentage of patients with decayed endometrium was 70 / 10 / 10. The development of the process suggested that the endometrial receptivity of P6 group was better than that of other groups. (II) the coverage area of the process: in P3 and P4 groups, the percentage of the process was higher than that in the other groups. (2) the percentage of the ectopic process in the P6 group was higher than that in the other groups (P 3 and P 4). The area of P5, P6 and P7 were higher than that of P3 and P4, respectively. The coverage area of the process was higher than that of the P5 and P7 groups, indicating that the endometrial receptivity of the P6 group was better than that of the other groups. The expression of integrin av 尾 3, HOXA10 and LIF protein was not different in P3vs.P4 group. However, the expression of integrin av 尾 3, HOXA10 and LIF protein in P3vs.P6 group and P6vs.P7 group was the highest, and the expression of molecular markers suggested that the endometrial receptivity of P6 group was the best. Conclusion: in the HRT regimen implemented in this experimental center, most of people received progesterone supplementation for 6 days, which may be the most suitable time for embryo implantation, according to the development of freeze-thawed embryos on day 3. Transplanting the 3rd day embryo into the uterus supplemented with progesterone for 3 days may be better synchronized.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R714.8

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