反复种植失败患者与复发性流产患者分泌期子宫内膜自然杀伤细胞数量分析

Quantitative analysis of natural killer cells in endometrium of secretory phase in women with repeated implantation failure or recurrent miscarriage

目的研究子宫内膜自然杀伤细胞(uNK)在反复种植失败(RIF)患者与复发性流产(RM)患者分泌期子宫内膜的表达情况。方法选取2013年3月至2016年10月于本院生殖医学助孕中心的RIF患者(20例)和RM患者(35例),对照25例。于患者尿LH试纸检测峰值出现后第7~9天,利用子宫内膜取样器刮取少量子宫腔内膜组织;根据子宫内膜形态学Noyes标准,确定RIF患者组(n=20)、RM患者组(n=35)与对照组(男性因素不孕患者,n=25)子宫内膜分期;以CD56作为uNK的表面标记物,免疫组化技术检测3组患者分泌期子宫内膜CD56阳性细胞的数量,并利用Vectra~自动病理成像定量分析系统计算细胞阳性细胞率。结果 3组患者内膜形态学分期均有早、中、晚分泌期病例;RIF组与RM组患者分泌期子宫内膜CD56阳性细胞率[分别为(17.59±12.59)%、(16.54±11.37)%]显著高于对照组[(8.01±7.19)%](P<0.01);3组患者子宫内膜CD56阳性细胞率从分泌早期到分泌晚期均呈显著递增趋势(P<0.05);RIF组与RM组分泌早期、中期及晚期CD56阳性细胞率均显著高于对照组(P<0.05)。结论 RIF与RM患者子宫内膜分泌早、中、晚期uNK细胞数量异常升高,提示其可能影响子宫内膜容受性,从而导致妊娠失败。

Objective: To investigate the natural killer cells(uNK)levels in endomitrium of secretory phase in the patients with repeated implantation failure(RIF)or recurrent miscarriage(RM).Methods: Endometrial samples were obtained with an endometrial curette from 7th day to 9th after the LH surge.Endometrial stage was determined according to the Noyes standard of endometrial morphology.The number of CD56 positive cells in endometrial biopsies was detected by immunohistochemical technique with CD56 as the surface marker of uNK in 25 normal control women whose infertility caused by male factors,20 women with RIF and 35 women with RM.The percentage of CD56^+ cells were analyzed by Vectra~automatic pathological imaging quantitative analysis system.Results: According to the Noyes standard of endometrial morphology,the endometrium in early-,mid-,late-secretory phase were confirmed in the patients of three groups.The percentage of uterine CD56^+ cells in secretory phase in RIF group [(17.59±12.59)%]or RM group [(16.54±11.37)%]was significantly higher than that in the control group[(8.01±7.19)%](P<0.01).The percentage of CD56+cells was gradually increased through the early-,mid-to late-secretory phase in all three groups(P<0.05).The percentage of CD56^+ cells in women with RM and RIF were significantly higher than that in normal control women in each phase(P<0.05).Conclusions: The abnormal increase of uNK number in endometrium of early-,mid-,latesecretory phase in patients with RIF and RM may affect the endometrial receptivity,thus lead to pregnancy failure.