复发性流产免疫治疗的循证争议与精准化转型

Evidence-Based Controversies and Precision Transformation in Immunotherapy for Recurrent Pregnancy Loss

摘要: 复发性流产(Recurrent Spontaneous Abortion, RSA)是育龄期女性中发生率约1%~5%的复杂生殖障碍，其中免疫因素被认为在不明原因RSA中发挥重要作用。本文旨在系统梳理各类免疫治疗方案在RSA中的循证医学证据，分析“证据–实践”差距的深层成因，并探讨精准化转型的方向与前景。方法上，本文采用文献综述的方法，检索PubMed、中国知网等数据库中2000年至2026年间关于RSA免疫治疗的相关文献，纳入静脉输注免疫球蛋白、糖皮质激素、淋巴细胞免疫治疗、脂肪乳、粒细胞集落刺激因子及间充质干细胞等主要免疫干预方案的研究证据，对RCT、Meta分析及临床指南进行系统梳理与批判性评估。结果表明，当前高质量证据不支持免疫治疗用于RSA的常规临床实践；但特定患者亚群——如高序RSA (≥4次)、继发性RSA——可能存在治疗获益。2025年美国生殖免疫学会首次发布的RSA免疫治疗指南为该领域提供了新的循证参考框架。结论认为，实现免疫治疗从“经验性应用”向“精准化干预”的转型，关键在于建立可靠的免疫学生物标志物体系、开展大样本良好分层的前瞻性随机对照试验，以及探索以间充质干细胞为代表的新型免疫调节策略。

Abstract: Recurrent Spontaneous Abortion (RSA) is a complex reproductive disorder affecting approximately 1% to 5% of women of childbearing age, with immunological factors considered to play a significant role in unexplained RSA. Despite the theoretical rationale provided by maternal-fetal immune tolerance mechanisms, the clinical efficacy and safety of various immunomodulatory interventions—including intravenous immunoglobulin (IVIG), corticosteroids, lymphocyte immunotherapy (LIT), lipid emulsions, and granulocyte colony-stimulating factor (G-CSF)—remain highly controversial after more than three decades of clinical exploration. This article aims to systematically review the evidence-based medical evidence for various immunotherapeutic regimens in RSA, analyze the underlying causes of the evidence-practice gap, and explore the directions and prospects for precision transformation. In terms of methodology, this review employed a literature synthesis approach, searching databases including PubMed and China National Knowledge Infrastructure (CNKI) for studies published between 2000 and 2026 on immunotherapy for RSA. Evidence from randomized controlled trials (RCTs), meta-analyses, and clinical practice guidelines was systematically reviewed and critically appraised. The results demonstrate that current high-quality evidence does not support the routine use of immunotherapy for all RSA patients in clinical practice. However, specific patient subgroups—including those with high-order RSA (≥4 losses) and those with secondary RSA—may derive potential therapeutic benefit. The first-ever guidelines for immunotherapy in RSA, published in 2025 by the American Society for Reproductive Immunology (ASRI), provide a new evidence-based reference framework for this controversial field. The conclusion emphasizes that achieving the transformation from empirical application to precision intervention in immunotherapy for RSA depends critically on three key elements: establishing reliable immunological biomarker systems for patient stratification, conducting large-scale, well-stratified prospective RCTs, and exploring novel immunomodulatory strategies represented by mesenchymal stem cells.