IVF-ET反复种植失败患者子宫内膜中miR-155、miR-21表达

Expression of miR-155 and miR-21 in endometrium of patients with recurrent implantation failure after IVF-ET

目的:检测微小RNA-155(miR-155)、微小RNA-21(miR-21)在体外受精-胚胎移植(IVF-ET)反复种植失败(RIF)患者子宫内膜中的表达,及对RIF的临床意义。方法:选取2018年1月—2019年12月在本院生殖医学中心行IVF-ET治疗的反复种植失败不孕症患者40例为RIF组,同期IVF-ET后妊娠成功患者40例为对照组。收集两组一般资料,均在IVF-ET前一月经周期黄体中期采集子宫内膜组织,实时荧光定量PCR(qRT-PCR)检测子宫内膜组织中miR-155、miR-21水平;取外周静脉血采取酶联免疫吸附法检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、IL-1β水平。在胚胎移植日行阴道B超检测子宫内膜容受性指标,即子宫内膜螺旋动脉搏动指数(PI)、阻力指数(RI)及子宫内膜厚度(Em)。Pearson法分析RIF患者子宫内膜miR-155、miR-21水平与炎症因子及子宫内膜容受性指标的相关性。二元logistic回归分析RIF的影响因素。结果:与对照组相比,RIF组子宫内膜中miR-155、miR-21表达水平、血清中TNF-α、IL-6、IL-1β水平及子宫内膜容受性指标PI、RI均升高,Em降低(均P<0.05)。RIF组患者子宫内膜miR-155、miR-21与TNF-α、IL-6、IL-1β、PI、RI呈正相关(P<0.05),与Em呈负相关(P<0.05)。logistic回归分析显示,TNF-α、IL-6、IL-1β、PI、RI及Em既不是危险因素也不是保护因素(P>0.05),miR-155、miR-21是影响IVF-ET妇女发生RIF的危险因素(P<0.05)。结论:RIF患者子宫内膜中miR-155、miR-21水平升高,可能作为潜在的诊断RIF的标志物。

Objective: To detect the expression of microRNA-155(miR-155) and microRNA-21(miR-21) in the endometrium of the patients with recurrent implantation failure(RIF) after in vitro fertilization and embryo transfer(IVF-ET), and to explore their clinical significance. Methods: 40 patients with RIF after IVF-ET from January 2018 to December 2019 were selected in RIF group, and 40 patients with successful pregnancy after IVF-ET were selected in control group during the same period. The general information of the patients in both groups was collected. The endometrial tissues of patients in both groups during the middle luteal phase were obtained before IVF-ET. Real-time fluorescence quantitative PCR(qRT-PCR) was used to detect the levels of miR-155 and miR-21 in endometrium of these patients. The levels of serum tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and interleukin-1β(IL-1β) in peripheral venous blood were detected by enzyme-linked immunosorbent assay(ELISA). The endometrial receptivity indictors were detected by B ultrasound on the embryo transfer day, which included endometrial spiral artery pulsatility index(PI), resistance index(RI) and endometrial thickness(Em). Pearson method was used to analyze the correlation of miR-155 and miR-21 levels of the patients with their inflammatory factors levels and endometrial receptivity indictors. The influencing factors of RIF were analyzed by binary Logistic regression. Results: Compared with those of the patients in the control group, the expression levels of miR-155 and miR-21 in the endometrium, the levels of serum TNF?α,IL-6 and IL-1β,and the endometrial receptivity indexes(PI and RI)of the patients in RIF group were significant higher,while EM of the patients in RIF group was significant lower(all P<0.05).In RIF group,the endometrial miR-155 and miR-21 levels of the patients were positively correlated with their serum TNF?α,IL-6,and IL-1βlevels,and their PI and RI values(P<0.05),bur were negatively correlated with their Em value(P<0.05).Logistic regression analysis showed that the levels of TNF?α,IL-6 and IL-1β,and the values of PI,RI,and Em were neither the risk factors nor the protective factors of the patients with RIF after IVF-ET(P>0.05),and miR-155 and miR-21 levels were the risk factors(P<0.05).Conclusion:The levels of miR-155 and miR-21 in endometrium of patients with RIF increase,which may be used as the potential markers for diagnosing their RIF.