【摘要】 反复妊娠丢失（recurrent pregnancy loss,RPL）影响2%～5%的育龄女性，病因复杂且其免疫治疗手段一直存在争议。20世纪90年代起，基于“免疫排斥”假说，静脉输注免疫球蛋白（IVIG）被用于RPL的免疫治疗。该治疗期望通过封闭父源抗原或抑制自然杀伤（NK）细胞活性来提高患者的活产率。30余年来，全球已完成多项随机双盲安慰剂对照试验及荟萃（Meta）分析，结论一致认为IVIG不能用于全部RPL的常规治疗。近几年的随机对照试验研究及Meta分析结果提示，≥4次流产的高序RPL患者可能从IVIG治疗中获益，并且该结论被纳入欧洲人类生殖与胚胎学学会（ESHRE）的RPL指南。关于IVIG治疗RPL的机制研究非常有限，近些年来的研究主要集中在其对外周血调节性T细胞（Treg细胞）和NK细胞的影响。也有研究表明，应用IVIG后细胞外囊泡的改变有利于妊娠维持。值得注意的是，IVIG在RPL的治疗中存在患者病因筛查不全、血源昂贵、治疗方案不一等现状，这些现状影响了大样本临床研究的实施及其效果。而且，目前尚无可靠生物标志物来界定哪些患者适合采用IVIG进行治疗。未来需建立统一病因评估体系，开展大样本多中心随机对照试验研究，方能逐步明确对IVIG治疗有效的患者亚群及免疫治疗指标。更多还原

【Abstract】 Recurrent pregnancy loss(RPL)affects 2%-5%of reproductive-age women. The etiology of RPL is heterogeneous and immunological treatment remains controversial. Since the 1990s the “immune rejection”hypothesis prompted the use of intravenous immunoglobulin(IVIG)to neutralize paternal antigens or suppress NK-cell activity and thereby improve live-birth rates. During the past three decades,multiple randomized double-blind placebo-controlled trials(RCTs)and metaanalyses have been completed globally,and the conclusion is unanimously that IVIG cannot be used as a routine treatment for all recurrent miscarriages. However,the results of randomized controlled trials and meta-analyses in recent years suggest that high-order RPL patients with ≥4 miscarriages may benefit from IVIG treatment,and this conclusion is recommonded by the ESRPLE guidelines for RPL. The mechanism research on IVIG treatment for RPL is very limited. In recent years,the mechanism research has focused on the effects of IVIG on Treg cells and NK cells in peripheral blood. Some studies have also shown that changes in extracellular vesicles after IVIG may be beneficial for pregnancy maintaince. It is worth noting that the studies of IVIG has limitations in RPL treatment,such as incomplete patient etiological screening,expensive blood sources,and inconsistent treatment plans,which have affected the implementation of large-scale clinical studies. Moreover,there is currently no reliable biomarker to define which patients are suitable for IVIG treatment. In the future,it is necessary to establish a unified etiology assessment system and conduct large-scale multicenter RCTs in order to gradually clarify the patient subgroups and immunotherapy indicators that are effective for IVIG treatment.更多还原