摘要
目的观察合并慢性子宫内膜炎(CE)的反复着床失败(RIF)患者子宫自然杀伤(uNK)细胞的表达水平。方法选取2018年10月—2023年2月就诊于生殖医学中心的82例RIF患者为RIF组;选择同期在本中心行体外受精-胚胎移植(IVF-ET)的有IVF助孕妊娠活产史且拟再次助孕的82例患者为对照组。2组均在黄体中期取2份子宫内膜组织,一份采用流式细胞仪检测子宫内膜CD56^(+)CD16^(+)uNK细胞水平,另一份采用免疫组化方法检测CD138。采集外周血3~4 mL,采用流式细胞仪检测CD56^(+)CD16^(+)外周血自然杀伤(CD56^(+)CD16^(+)PbNK)细胞水平及血常规。CE阳性患者口服抗生素治疗1个疗程。抗炎治疗结束后下个月经周期黄体期时再次取少量子宫内膜组织,采用免疫组化方法检测CD138。比较治疗前后2组临床妊娠率及胚胎着床率。结果RIF组CD56^(+)CD16^(+)uNK细胞水平为(34.23±17.01)%,低于对照组的(45.41±20.90)%,差异有统计学意义(P<0.05);RIF组黄体中期外周血中CD56^(+)CD16^(+)PbNK细胞水平为(14.38±5.36)%,与对照组的(13.58±4.34)%比较,差异无统计学意义(P>0.05);RIF组与对照组白细胞计数、淋巴细胞百分比、中性粒细胞百分比比较,差异无统计学意义(P>0.05)。子宫内膜CD56^(+)CD16^(+)uNK细胞水平与外周血CD56^(+)CD16^(+)PbNK细胞水平无相关性(r=0.06)。RIF组合并CE与无合并CE、对照组合并CE与无合并CE的黄体中期内膜中CD56^(+)CD16^(+)uNK细胞、外周血中CD56^(+)CD16^(+)PbNK细胞水平比较,差异均无统计学意义(P>0.05)。在RIF组合并CE及对照组合并CE患者中,治疗后CE转阴者较CE仍为阳性者的临床妊娠率、着床率均升高,早期流产率降低,差异均有统计学意义(P<0.05)。结论CD56^(+)CD16^(+)uNK细胞低表达可能导致母胎界面免疫紊乱,从而增加RIF发生的风险;外周血CD56^(+)CD16^(+)PbNK细胞与子宫内膜CD56^(+)CD16^(+)uNK细胞无相关性;抗生素治疗CE能明显改善RIF患者妊娠结局,CE的确诊和治疗应作为RIF评估的重要因素。
Objective To observe the expression level of uterine natural killer(uNK)cell in patients with repeated implantation failure(RIF)complicated with chronic endometritis(CE).Methods A total of 82 RIF patients treated in the Reproductive Medicine Center from October 2018 to February 2023 were selected as RIF group;82 cases with history of IVF-assisted pregnancy and willing of assisted pregnancy again in the same period who underwent in vitro fertilization-embryo transfer(IVF-ET)in the center were selected as control group.Two samples of endometrial tissues were taken from both groups during the mid-luteal phase,one sample was used for detection of endometrial CD56^(+)CD16^(+)uNK cell level by flow cytometry,and another sample was used for detection of CD138 by immunohistochemistry.A sample of 3 to 4 mL peripheral blood was collected,and flow cytometry was used to detect the level of CD56^(+)CD16^(+)peripheral blood natural killer(CD56^(+)CD16^(+)PbNK)cell and blood routine.Patients with positive CE were asked to take a course of oral antibiotic therapy.In the luteal phase of the next menstrual cycle after the end of anti-inflammatory treatment,a small amount of endometrial tissues was taken again,and CD138 was detected by immunohistochemistry.Clinical pregnancy rate and embryo implantation rate before and after treatment were compared between the two groups.Results The level of CD56^(+)CD16^(+)uNK cell was(34.23±17.01)%in the RIF group,which was significantly lower than(45.41±20.90)%in the control group(P<0.05);the level of CD56^(+)CD16^(+)PbNK cell in the peripheral blood of the mid-luteal phase in the RIF group was(14.38±5.36)%,which showed no significant difference compared to(13.58±4.34)%in the control group(P>0.05);there were no significant differences in white blood cell count,lymphocyte percentage,and neutrophil percentage between the RIF group and the control group(P>0.05).There was no correlation between the level of endometrial CD56^(+)CD16^(+)uNK cell and the level of CD56^(+)CD16^(+)PbNK cell in peripheral blood(r=0.06).There were no significant differences in the levels of endometrial CD56^(+)CD16^(+)uNK cell and peripheral blood CD56^(+)CD16^(+)PbNK cell in mid-luteal phase between cases with CE and without CE in the RIF group and the control group(P>0.05).In the patients complicating CE in the RIF group and the control group,the clinical pregnancy rate and implantation rate of cases with negative CE after treatment were significantly higher than those with positive CE after treatment,while the early abortion rate of cases with negative CE after treatment was significantly lower(P<0.05).Conclusion Low expression of CD56^(+)CD16^(+)uNK cell may lead to immune disorders at the maternal-fetal interface,thereby increasing the risk of RIF;there is no correlation between peripheral blood CD56^(+)CD16^(+)PbNK cell and endometrial CD56^(+)CD16^(+)uNK cell;antibiotic treatment for CE can significantly improve the pregnancy outcome of RIF,and the diagnosis and treatment of CE should be considered as an important factor in the evaluation of RIF.
作者
黎俏
余建华
薛永杰
陈海霞
赖放颖
全燕
何韶坚
翁光明
高天旸
LI Qiao;YU Jianhua;XUE Yongjie;CHEN Haixia;LAI Fangying;QUAN Yan;HE Shaojian;WENG Guangming;GAO Tianyang(the Second School of Clinical Medicine of Southern Medical University,Guangzhou,Guangdong,510515;Department of Reproductive Medicine,Dongguan Kanghua Hospital,Dongguan,Guangdong,523080;Laboratory of Blood Center,Dongguan Kanghua Hospital,Dongguan,Guangdong,523080;Department of Pathology,Dongguan Kanghua Hospital,Dongguan,Guangdong,523080;Center for Reproductive Medicine,Guangdong Second Provincial General Hospital,Guangzhou,Guangdong,510310)
出处
《实用临床医药杂志》
2023年第16期101-106,110,共7页
Journal of Clinical Medicine in Practice
基金
广东省中医药局科研资助项目(20191013)
2023年广东省东莞市社会发展科技面上项目(20231800902612)。
关键词
反复着床失败
慢性子宫内膜炎
自然杀伤细胞
辅助生殖技术
生殖免疫
repeated implantation failure
chronic endometritis
natural killer cells
assisted reproductive technology
reproductive immunity
