反复种植失败患者种植窗期子宫自然杀伤细胞功能相关参数的分析及其临床意义  

Analysis of parameters related to uNK cell function during the implantation window and their clinical significance in patients with recurrent implantation failure

作　　者：张津 张信贤 吴小华[1] ZHANG Jin;ZHANG Xin-xian;WU Xiao-hua(Reproductive Medicine Center,The Fourth Hospital of Shijiazhuang,Key Laboratory of Maternal and Fetal Medicine of Hebei Province,Shijiazhuang 050000)

机构地区：[1]石家庄市第四医院生殖医学中心河北省母胎医学重点实验室,石家庄050000

出　　处：《生殖医学杂志》2024年第11期1430-1436,共7页Journal of Reproductive Medicine

基　　金：河北省自然科学基金(H2023106006)。

摘　　要：目的 探究种植窗期子宫自然杀伤(uNK)细胞的发育和功能状况与不明原因反复种植失败(RIF)的关联。方法 收集2021年9月至2023年8月在石家庄市第四医院生殖医学中心行IVF-ET助孕的61例患者的临床数据及其黄体中期内膜样本,根据移植周期结果分为RIF组(种植失败≥3个周期,n=39)和对照组(助孕1个周期即获得临床妊娠,n=22)。采用免疫组织化学(IHC)法检测uNK细胞并计算百分比,采用逆转录多聚合酶链式反应(RT-PCR)测定子宫内膜白介素15(IL-15)、成纤维细胞生长因子诱导分子14(Fn-14)、白介素18(IL-18)及肿瘤坏死因子样弱凋亡诱导因子(TWEAK)的mRNA水平,并计算IL-15/Fn-14 mRNA和IL-18/TWEAK mRNA比值,比较两组患者的一般资料和妊娠结局,分析uNK细胞功能参数间的差异。结果 RIF组和对照组间的年龄、体质量指数(BMI)、基础窦卵泡数(AFC)、移植日内膜厚度、不孕年限、不孕类型、抗苗勒管激素(AMH)和基础性激素水平比较,差异均无统计学意义(P>0.05)。RIF组的移植周期数及胚胎移植数目显著高于对照组(P<0.05);两组间的移植胚胎种类比较无显著性差异(P>0.05)。RT-PCR结果显示,IL-15、Fn-14、IL-18及TWEAK的mRNA水平在两组间无显著差异(P>0.05),但RIF组中的IL-15/Fn-14 mRNA及IL-18/TWEAK mRNA比值均显著高于对照组(P<0.05)。uNK细胞功能分析中,与对照组相比,RIF组黄体中期子宫内膜uNK细胞百分比显著升高(4.0%vs.3.0%,P<0.05),且IL-18/TWEAK mRNA比值紊乱比例显著上升(56.4%vs.45.5%,P<0.05),其中过度激活占51.3%,低激活占5.1%。结论 RIF可能与种植窗期uNK细胞的过度激活和激活不足有关。Objective:To explore the correlation between the developmental and functional status of uterine natural killer(uNK)cells during the implantation window and recurrent implantation failure(RIF).Methods:From September 2021 to August 2023,the clinical data of patients who underwent IVF-ET at the Reproductive Medicine Center of the Fourth Hospital of Shijiazhuang and their mid-luteal endometrium were obtained.A total of 61 patients were included.The patients were divided into RIF group(implantation failure≥3 cycles,n=39)and control group(clinical pregnancy achieved with 1 cycle,n=22)according to the results of transplantation cycles.Immunohistochemistry(IHC)was used to detect and count the percentage of uNK cells.RT-PCR was used to determine the mRNA level of interleukin(IL)-15,fibroblast growth factor-inducible molecule 14(Fn-14),IL-18 and tumor necrosis factor(TNF)-like weak inducer of apoptosis(TWEAK)and count the ratio of IL-15/Fn-14 mRNA and IL-18/TWEAK mRNA.The basic characteristics and pregnancy outcomes between the two groups were compared,and the differences among the parameters related to uNK cell function were analyzed.Results:There were no significant differences in age,body mass index(BMI),antral follicle count(AFC),endometrial thickness on the day of ET,infertility duration,type of infertility,anti-Müllerian hormone(AMH)and basal hormone levels between the RIF group and the control group(P>0.05).The number of transfer cycle and embryo transferred in RIF group were significantly higher than those of the control group(P<0.05).The type of embryo transferred was the same in the two groups(P>0.05).The RT-PCR results showed that the mRNA levels of IL-15,Fn-14,IL-18 and TWEAK were not significantly different between the two groups(P>0.05),but the IL-15/Fn-14 and IL-18/TWEAK ratios were significantly higher in the RIF group than in the control group(P<0.05).In the uNK cell function analysis,compared with the control group,the percentage of endometrial uNK cells was significantly increased in the RIF group(4.0

关 键 词：反复种植失败 种植窗 子宫自然杀伤细胞 细胞功能 

分 类 号：R711.6[医药卫生—妇产科学]