hCG共培养自体PBMCs宫腔灌注治疗反复种植失败及相关机制的研究

目的:探讨人绒毛膜促性腺激素(hCG)共培养自体外周血单个核细胞(PBMCs)宫腔灌注对反复种植失败(RIF)患者妊娠结局的影响及宫腔内相关细胞因子的改变。方法:选择在我院生殖中心行冻融胚胎移植(FET)的RIF患者65例,接受移植前自体PBMCs宫腔灌注治疗及取宫腔液的患者28例为实验组,于排卵前抽取自体外周血分离PBMCs,与hCG混合共培养于移植前3天行宫腔灌注;另外37例为对照组,两组患者行常规FET,随访妊娠结局;Bio-plex悬液芯片分析系统检测灌注前、后宫腔液相关细胞因子。结果:两组患者年龄、不孕年限、体质量指数(BMI)、基础性激素水平(FSH、LH、E2)、既往移植周期数、平均内膜厚度和移植胚胎数比较,差异均无统计学意义(P>0.05)。实验组与对照组比较临床妊娠率(42.86%vs16.22%)和胚胎种植率(25.86%vs9.21%),实验组均高于对照组,差异有统计学意义(P<0.05)。宫腔灌注后宫腔液中Eotaxin表达水平升高,而INF-γ表达降低,差异有统计学意义(P<0.05)。结论:宫腔灌注hCG共培养PBMCs是一项针对RIF患者安全有效的治疗方法,可以提高此类患者FET周期的临床妊娠率,改善RIF患者宫腔局部细胞因子的表达,促进胚胎种植。

Effect of hCG-Activated Autologous PBMCs Intrauterine Administration for Repeated Implantation Failure

Objective:To explore the effect and the potential mechanism of intrauterine administration with HCG-activated autologous PBMCs on pregnancy outcomes and changes of intrauterine cytokines in patients with recurrent implantation failure(RIF).Methods:A total of 65 RIF patients received frozen-thawed embryo transfer(FET)were enrolled,and 28 patients in research group received autologous PBMCs intrauterine perfusion therapy and uterine fluid extraction before the frozen-thawed embryo transfer while the other 37 were in the control group.PBMCs were isolated from autologous peripheral blood before ovulation and co-cultured with HCG for intrauterine perfusion 3 days before transplantation.Routine FET was performed in both groups and pregnancy outcomes were collected.The cytokines related to uterine secretions were detected before and after intrauterine administration by Bio-plex chip analysis system.Results:There were no significant differences in age,infertility years,basic sex hormone levels,the number of previous transplant cycles,the mean intimal thickness and the number of embryos transferred between the two groups(P>0.05).The clinical pregnancy rate(42.86%vs 16.22%)and implantation rate(25.86%vs 9.21%)in the research group were significantly higher than those in the control group.The expression of Eotaxin in uterine secretions increased after intrauterine administration(P<0.05),while the expression of INF-γdecreased(P<0.05).Conclusions:Intrauterine administration of HCG co-cultured PBMCs is a safe and effective treatment for RIF patients,which could improve the clinical pregnancy rate of FET cycles and ameliorate the expression of local cytokines in uterine cavity to promote embryo implantation.