反复种植失败患者子宫内膜MUM1阳性表达与子宫内膜血流变化的关系

Association between positive MUM1 expression and endometrial blood flow changes in patients with repeated implantation failure

目的:探讨反复种植失败(repeated implantation failure,RIF)患者子宫内膜中多发性骨髓瘤癌基因1(multiple myeloma oncogene 1,MUM1)阳性表达与子宫内膜血流变化的关系。方法:回顾性队列研究分析选择2022年3月至2023年5月期间在郑州大学第二附属医院生殖医学中心就诊的62例RIF患者为研究对象。所有患者于围排卵期都接受宫腔镜检查,采集子宫内膜组织,并通过免疫组织化学染色法检测子宫内膜组织MUM1、血管内皮生长因子(vascular endothelial growth factor,VEGF)、微血管密度(microvessel density,MVD)的阳性表达情况,并行三维多普勒超声子宫内膜血流动力学检查,根据MUM1表达的结果分为MUM1阳性组(29例)和MUM1阴性组(33组),比较两组患者子宫内膜厚度、子宫内膜血流血管化指数(vascularization index,VI)、血流指数(blood flow index,FI)、血管化血流指数(vascularized blood flow index,VFI)及双侧子宫动脉血流阻力指数(resistance index,RI)、搏动指数(pulsatility index,PI)、收缩期峰值流速与舒张末期流速比值(peak systolic velocity/peak diastolic velocity,S/D)的参数;比较两组患者中子宫内膜VEGF、MVD的表达水平;采用Pearson相关性分析,探讨两组子宫内膜VEGF、MVD的表达与子宫内膜血流VI、FI、VFI的相关性。结果:在RIF患者中,MUM1阳性组子宫内膜VEGF阳性率[31.03%(9/29)]、MVD的表达(16.97±3.28)及子宫内膜VI(1.45±0.96)、FI(21.13±5.33)、VFI(0.39±0.17)明显低于MUM1阴性组[36.36%(12/33),P<0.001;33.42±7.97,P<0.001;1.91±0.56,P=0.025;23.91±5.37,P=0.045;0.54±0.14,P=0.004]。MUM1阳性组双侧子宫动脉血流RI(0.69±0.14)、PI(1.49±0.61)、S/D(2.40±0.62)显著大于MUM1阴性组(0.54±0.15、0.92±0.34、1.45±0.40;均P<0.001)。MUM1阳性组子宫内膜MVD的表达水平与子宫内膜血流VI、FI、VFI存在显著正相关(r=0.931,P<0.001;r=0.968,P<0.001;r=0.914,P<0.001),子宫内膜VEGF的表达与子宫内膜血流VI、FI、VFI也存在显著正相关(r=0.965,P<0.001;r=0.954,P<0.001;r=0.935,P<0.001)。结论:在RIF患者中,MUM1阳性表达影响子宫内膜血流及VEGF、MVD的表达水平,且子宫内膜血流VI、FI、VFI与子宫内膜VEGF、MVD的表达呈显著正相关。

ObjectiveTo investigate the relationship between positive expression of multiple myeloma oncogene 1(MUM1)and changes of endometrial endometrium in patients with repeated implantation failure(RIF).MethodsA retrospective cohort study of 62 RIF patients who attended the Center for Reproductive Medicine of the Second Affiliated Hospital of Zhengzhou University between March 2022 and May 2023 were selected.All patients were examined by perimetry,endometrial tissue was collected,and the positive expression of MUM1,vascular endothelial growth factor(VEGF),and microvessel density(MVD)were detected by immunohistochemical staining.The endometrial hemodynamics were examined by three-dimensional Doppler ultrasound,and according to the results of MUM1 expression,the patients were divided into MUM1-positive group(29 cases)and MUM1-negative group(33 cases).The endometrial thickness,endometrial blood flow vascularization index(VI),flow index(FI),vascularized blood flow index(VFI),and bilateral uterine arterial blood flow resistance index(RI),pulsatility index(PI),peak systolic velocity/peak diastolic velocity(S/D)were compared between the two groups.The expression levels of endometrial VEGF and MVD were compared between the two groups.Pearson correlation was used to explore the correlation between the expression of endometrial VEGF,MVD and endometrial blood flow VI,FI,VFI in the two groups.ResultsIn RIF patients,the endometrial VEGF positivity rate[31.03%(9/29)],MVD expression(16.97±3.28),and endometrial VI(1.45±0.96),FI(21.13±5.33),and VFI(0.39±0.17)in MUM1-positive group were significantly lower than those in the MUM1-negative group[the VEGF-positive rate:36.36%(12/33),P<0.001;MVD:33.42±7.97,P<0.001;VI:1.91±0.56,P=0.025;FI:23.91±5.37,P=0.045;VFI:0.54±0.14,P=0.004].Bilateral uterine arterial blood flow RI(0.69±0.14),PI(1.49±0.61),S/D(2.40±0.62)in MUM1-positive group was significantly higher than those in MUM1-negative group(0.54±0.15,0.92±0.34,1.45±0.40;all P<0.001).There was a significant positive correlation between the endometrial MVD expression level in the MUM1-positive group and endometrial blood flow of VI,FI,and VFI(r=0.931,P<0.001;r=0.968,P<0.001;r=0.914,P<0.001),and there was also a significant positive correlation between endometrial VEGF expression and endometrial blood flow VI,FI,and VFI(r=0.965,P<0.001;r=0.954,P<0.001;r=0.935,P<0.001).ConclusionIn RIF patients,the positive expression of MUM1 affects endometrial blood flow and the expression levels of VEGF and MVD,and there is a significant positive correlation between endometrial blood flow VI,FI,VFI and the expression of VEGF and MVD in the endometrium.