超排卵周期中高雌孕激素对子宫内膜ER、PR、HOX10以及内膜容受性的影响

Effects of High Estradiol and Progesterone Levels in Controlled Ovarian Hyperstimulation Cycles on ER, PR, HOX10 and Endometrial Receptivity

摘要: 目的：通过检测雌激素受体ER、孕激素受体PR、同源框基因HOXA-10在控制性超排卵(COH)患者的胚胎着床窗口期子宫内膜中的表达，探讨IVF超促排卵过程中超生理剂量的雌激素、孕激素对子宫内膜容受性的影响，及其可能机制。方法：因卵巢过度刺激综合征因卵巢过度刺激综合征或过高孕酮水平而取消鲜胚移植的59例不孕症患者作为研究对象，根据HCG日雌、孕激素水平将研究对象分为三组：高雌激素组(E2 ≥ 5210 pg/ml且P < 1.05 ng/ml)、高孕酮组(P ≥ 1.05 ng/ml且E2 < 5210 pg/ml)、高雌激素合并高孕酮组(E2 ≥ 5210 pg/ml且P ≥ 1.05 ng/ml)，于取卵后7~8天用宫腔负压吸管(Pipelle管)取内膜组织；10例排卵正常、拟行冷冻移植的患者作为对照组，于排卵后7~9天同法取内膜，采用免疫组化SP法和组织学积分H-score法对ER、PR、HOXA-10在种植窗口期子宫内膜中的表达进行定位和半定量分析，比较不同雌、孕激素水平在着床期对上述三个指标表达的影响，从而推测超促排卵中高雌、孕激素对子宫内膜容受性的影响。结果：与对照组相比，高雌激素组ER、PR、HOXA-10的表达无明显差异，而高孕酮组、高雌合并高孕酮组的上述指标的表达均明显下降。结论：辅助生殖技术中，COH引起的高雌激素状态可能对子宫内膜容受性无明显影响，而高孕激素则使子宫内膜容受性下降。

Abstract: Objective: To study the expressions of ER, PR and HOX10 in endometrium during the pe-ri-implatation period after controlled ovarian hyperstimulation (COH); To explore the influence of high estradiol and progesterone levels in COH cycles to endometrial receptivity. Methods: 59 in-fertile women undergoing COH cancelled embryo transfer because of ovarian hyperstimulation syndrome (OHSS) or excessive high progesterone level were selected as study groups, then they were divided into three groups according to serum estradiol and progesterone concentrations on the day of human chorionic gonadotrophin (hCG) administration: high estradiol group (estradiol ≥ 5210 pg/ml, progesterone < 1.05 ng/ml), high progesterone group (progesterone ≥ 1.05 ng/ml, estradiol < 5210 pg/ml), and high estradiol + high progesterone group (progesterone ≥ 1.05 ng/ml, estradiol ≥ 5210 pg/ml). Endometrial biopsy was performed at 7~8 days after oocytes retrieval by using Pipelle tubes. Ten ovulation-normal FET women were selected as control group; endometrial biopsy was performed using the same method after the seventh day of ovulation. Positioning analy-sis and semi-quantitative analysis of ER, PR and HOX10 expressions in endometrium during the window of implantation were conducted by immunohistochemical SP method and H-score method; the influences of different estradiol and progesterone levels during implantation period on ER, PR and HOX10 expressions were compared to speculate the effects of high estradiol and progesterone levels on endometrial receptivity in COH. Results: There was no statistically significant difference in the expressions of ER, PR and HOX10 among high estradiol group and control group. However, there were statistically significant differences among high estradiol + high progesterone group, high progesterone group and control group (P < 0.05). Conclusions: There was no connection between the high estradiol levels in COH cycles and endometrial receptivity. However, the high progesterone levels reduced endometrial receptivity significantly.