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封闭抗体阴性的反复种植失败患者淋巴细胞主动免疫治疗助孕结局的影响因素分析OACSTPCD

Analysis of factors influencing the outcome of lymphocyte active immunotherapy in patients with negative blocking antibody and repeated implantation failure

中文摘要英文摘要

目的 探究淋巴细胞主动免疫治疗(LIT)对反复种植失败的封闭抗体(BA)阴性患者助孕结局的影响及相关因素分析.方法 选取2021年1月至2023年2月在我院自愿进行辅助生殖的BA阴性且反复种植失败患者84例作为研究对象.所有患者均接受LIT治疗,根据治疗后是否助孕成功划分为助孕成功组(n=58)和助孕失败组(n=26).对比两组患者一般临床资料[年龄、配偶年龄、体质量指数(BMI)、流产次数、不孕持续时间、窦卵泡数]、LIT治疗相关特征(LIT制剂浓度、治疗次数、BA阳性率),以及治疗前性激素及抗苗勒管激素(AMH)水平、免疫细胞水平(CD4+T细胞比例、CD8+T细胞比例、CD4+/CD8+比值)及炎症因子水平[干扰素y(IFN-y)、白细胞介素4(IL-4)、白细胞介素10(IL-10)、白细胞介素17(IL-17)、转化生长因子β(TGF-β)].通过Spearman相关性分析、多因素Logistic回归分析法筛选接受LIT治疗的反复种植失败BA阴性患者助孕成功的影响因素.结果 两组患者一般临床资料及基础激素水平比较无统计学差异(P>0.05).助孕成功组患者平均LIT制剂浓度及BA阳性率均显著高于助孕失败组患者(P<0.05);助孕成功组患者治疗前CD4+T细胞比例及CD4+/CD8+比值均显著高于助孕失败组患者(P<0.05);助孕成功组患者治疗前血清IL-4、IL-10和TGF-β水平显著高于助孕失败组患者(P<0.05),而血清IL-17水平显著低于助孕失败组患者(P<0.05).Spearman相关性分析及多因素Logistic回归分析表明,BA阳性、LIT制剂浓度较高、CD4+T细胞比例较高、CD4+/CD8+比值较高、血清IL-4、IL-10、TGF-β水平较高、IL-17水平较低均是接受LIT治疗的反复种植失败BA阴性患者助孕成功的重要影响因素(P<0.05).结论 反复种植失败的BA阴性患者接受LIT可有效使BA转阳,其中使用LIT制剂浓度较高、促炎性细胞因子水平较低、抗炎性细胞因子水平及免疫细胞水平较高且BA转阳率较高的患者更容易在辅助生殖策略下助孕成功.

Objective:To explore the effects of lymphocyte active immunotherapy(LIT)on pregnancy outcomes of patients with negative blocking antibody(BA)after repeated implantation failure. Methods:Eighty-four BA negative and repeated implant failure patients who volunteered for assisted reproduction in Second Affiliated Hospital of Hainan Medical College from January 2021 to February 2023 were selected as the study group.All patients received LIT treatment and were divided into successful assisted pregnancy group(n=58)and failed assisted pregnancy group(n=26)according to assisted pregnancy outcomes after treatment.General clinical data[age,age of spouse,body mass index(BMI),number of abortions,duration of infertility,number of antral follicles]and characteristics related to LIT treatment(LIT preparation concentration,number of treatments,BA positive rate)as well as pre-treatment sex hormone and anti-Müllerian hormone(AMH)levels,immune cell levels(percentages of CD4+T cell and CD8+T cell,CD4+/CD8+ratio)and inflammatory factor levels[interferon gamma(IFN-γ),interleukin(IL)-4,IL-10,IL-17,transforming growth factor(TGF)-β]were compared between the two groups.Spearman correlation analysis and multivariate logistic regression analysis were used to screen the factors influencing the success of assisted pregnancy in BA negative patients with repeated implant failure treated with LIT. Results:There were no statistical differences in general clinical data and basal hormone levels between the two groups(P>0.05).The average concentration of LIT and the positive rate of BA in successful pregnancy group were significantly higher than those in failed pregnancy group(P<0.05).The percentage of CD4+T cells and CD4+/CD8+ratio in patients with successful pregnancy were significantly higher than those in patients with failed pregnancy before treatment(P<0.05).The serum IL-4,IL-10 and TGF-βlevels of patients with successful pregnancy were significantly higher than those of patients with failed pregnancy(P<0.05),while the serum IL-17 level was significantly lower(P<0.05).Spearman correlation analysis and multivariate Logistic regression analysis results showed that BA positive transforming,higher concentration of LIT preparation,higher percentage of CD4+T cells,higher ratio of CD4+/CD8+,higher levels of IL-4,IL-10,TGF-β and lower level of IL-17 were important factors influencing successful pregnancy in BA negative patients receiving LIT treatment(P<0.05). Conclusions:LIT can effectively convert BA into positive among BA negative patients with repeated implantation failure,and patients with higher concentration of LIT preparation,lower levels of proinflammatory cytokines,higher levels of anti-inflammatory cytokines and immune cells,and higher BA conversion rate are more likely to succeed in assisted reproduction strategy.

胡英;黄勇

海南医学院第二附属医院生殖医学科,海口 570100

临床医学

淋巴细胞主动免疫治疗封闭抗体阴性反复种植失败辅助生殖

Leukocyte immunization therapyBlocking antibody negativeRepeated implantation failureAssisted reproduction

《生殖医学杂志》 2024 (007)

893-899 / 7

海南省卫生健康行业科研项目(20A200432)

10.3969/j.issn.1004-3845.2024.07.008

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