Effect of parental lymphocyte immunotherapy on recurrent spontaneous abortion and repeated implantation failure
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目的:观察分析丈夫淋巴细胞主动免疫治疗(LIT)对不明原因复发性流产(uRSA)和反复着床失败(RIF)的妊娠结局的影响.方法:回顾性收集、分析具有uRSA、RIF的女性接受丈夫外周血淋巴细胞主动免疫治疗后封闭抗体转归情况及其妊娠结局,共收集 2019年 1月—2020年 12月在武汉大学人民医院生殖中心 250例因uRSA和RIF而行LIT的患者作为研究对象,其中uRSA组181例,RIF组69例.结果:①经过LIT后,治疗患者的整体封闭抗体转阳率为 86.8%;其中uRSA组的封闭抗体转阳率为 86.2%,RIF组的封闭抗体转阳率为 88.4%;②经过LIT治疗后,uRSA患者的妊娠率为 90.06%,流产率为 7.66%,活产率为 89.57%;RIF患者的妊娠率为66.67%,流产率为6.52%,活产率为93.48%.uRSA患者封闭抗体转阳组(+)与持续阴性组(-)的临床妊娠率、流产率、活产率差异无统计学意义(P>0.05);RIF患者封闭抗体转阳组(+)与持续阴性组(-)相比,临床妊娠率明显提高(72.1%vs 25.0%,P<0.05),流产率与活产率差异无统计学意义(P>0.05);③57名uRSA患者经过LIT治疗后行IVF助孕,其中<38岁的患者 47名,与≥38岁患者相比,其获卵数(14.38±6.31 vs 9.20±5.08)、2PN受精数(10.28±4.89 vs 6.20±3.82)、囊胚形成率(56.61%vs 38.64%)、胚胎着床率(51.04%vs 22.73%)、临床妊娠率(85.11%vs 50.00%)、活产率(92.5%vs 60.0%)明显升高,流产率降低(7.5%vs 40.0%),差异具有统计学意义(均P<0.05);④64名RIF患者经过LIT治疗后行IVF助孕,其中<38岁的患者56名,与≥38岁患者相比,其获卵数(13.39±6.48 vs 6.50±5.10,P=0.006)、2PN受精数(9.98±5.23 vs 4.75±3.07,P=0.008)、可移植胚胎数(6.18±3.54 vs 2.88±1.27,P=0.012)较高且有统计学差异;而胚胎着床率(44.74%vs 20.00%,P=0.068)、临床妊娠率(69.64%vs 37.50%,P=0.073)、活产率(94.87%vs 100%,P=0.688)较高,流产率较低(5.13%vs 0%,P=0.688),但差异没有统计学意义.结论:LIT能明显改善uRSA与RIF患者的妊娠结局.LIT强化治疗后封闭抗体的转阳情况对于RIF患者的临床妊娠率明显相关.uRSA和RIF经过LIT治疗后行IVF助孕的患者中,<38岁的患者妊娠结局有明显改善,≥38岁高龄患者由于胚胎非整倍体高,PGT-A联合LIT对改善这部分患者预后更好.
Objective:To investigate the effects of lymphocyte immunotherapy(LIT)on the outcomes of re-current spontaneous abortion and repeated implantation failure.Methods:The cases with a history of unexplained recurrent spontaneous abortion(uRSA)and recurrent implantation failure(RIF)were in-cluded,and all the cases received active immunotherapy with peripheral blood lymphocytes from their husbands.Their retrospectively blocking antibody outcomes and pregnancy outcomes were studied.A total of 250 patients who underwent LIT due to uRSA and RIF in the Reproductive Center of Ren-min Hospital of Wuhan University from January 2019 to December 2020 were collected as the re-search objects,including 181 patients in the uRSA group and 69 patients in the RIF group.Results:①After LIT,the overall blocking antibody conversion rate was 86.8%(217/250).The conversion rate of blocking antibodies in the uRSA group was 86.2%(156/181),and that in RIF group was 88.4%(61/69).②After LIT,the pregnancy rate,abortion rate,and live birth rate of uRSA patients were 90.06%,7.66%,and 89.57%,respectively.The pregnancy rate of the RIF patients was 66.67%,the abortion rate was 6.52%,and the live birth rate was 93.48%.There was no significant difference in the clinical pregnancy rate,abortion rate,and live birth rate between the positive block-ing antibody group(+)and the persistent negative group(-)in RSA patients(P>0.05).③A total of 57 uRSA patients underwent IVF after LIT,including 47 patients aged<38 years.Compared with those in the patients aged≥38 years,the number of oocytes(14.38±6.31 vs 9.20±5.08,P=0.018),and the number of 2PN fertilization(10.28±4.89 vs 6.20±3.82,P=0.016)were signifi-cantly more,and the blastocyst formation rate(56.61%vs 38.64%,P=0.016),embryo implanta-tion rate(51.04%vs 22.73%,P=0.003),clinical pregnancy rate(85.11%vs 50%,P=0.013),and live birth rate(92.5%vs 60%,P=0.029)were significantly higher in the patients aged<38 years,while the abortion rate was less(7.5%vs 40%,P=0.029).④A number of 64 RIF patients underwent IVF after LIT,including 56 patients aged<38 years.Compared with those in the patients aged≥38 years,the number of oocytes(13.39±6.48 vs 6.50±5.10,P=0.006),the number of 2PN fertilization(9.98±5.23 vs 4.75±3.07,P=0.008),and the number of transferable embryos(6.18±3.54 vs 2.88±1.27,P=0.012)were significantly more in the patients aged<38 years,while the embryo implantation rate(44.74%vs 20%,P=0.068)and the clinical pregnancy rate(69.64%vs 37.5%,P=0.073)were higher,the live birth rate(94.87%vs 100%,P=0.688)and the abortion rate(5.13%vs 0%,P=0.688)were lower,but the difference was not statistically signif-icant.Conclusion:LIT can significantly improve pregnancy outcomes in uRSA and RIF patients.The positive conversion of blocking antibodies after intensive LIT therapy is significantly related to the clinical pregnancy rate of RIF patients.Among the patients with uRSA and RIF who underwent IVF after LIT,the pregnancy outcome of patients aged<38 years was significantly improved.The elderly patients aged≥38 years had higher embryo aneuploidy,and PGT-A combined with LIT could improve the prognosis of these patients.
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