Abstract:

The etiology of recurrent spontaneous abortion (RSA) is complex, and immune is an important factor of the occurrence and development of RSA. The pathological mechanisms of RSA caused by immune abnormalities include: autoimmune diseases represented by antiphospholipid syndrome and systemic lupus erythematosus; alloimmune abnormalities centered on maternal-fetal immune rejection; and pathological inflammatory responses that run through multiple etiologies. These factors lead to pregnancy loss by affecting embryo implantation, placentation, and inducing thrombosis. The current clinical application status and evidence of various immunosuppressive therapies are as follows: ①Classic immunosuppressants such as glucocorticoids, hydroxychloroquine, and calcineurin inhibitors remain the mainstay for the treatment of RSA associated with autoimmune abnormalities. However, the indication and safety must be strictly controlled. ②Biologic targeted drugs, including tumor necrosis factor-α inhibitors and interleukin inhibitors, provide a new "precision" intervention direction for the refractory cases that fail conventional treatment, although they are still in the exploratory stage. ③Immunoglobulin and peripheral blood mononuclear cell therapy have shown the potential in patients with specific immune abnormalities, but the efficacy requires to be validated by higher-level evidence. Although immunosuppressive therapy has moved from empirical use to a more targeted stage, the overall treatment system remains incomplete. In the future, multi-omics technologies should be employed to deepen the study of mechanism, to discover more biomarkers that accurately predict therapeutic efficacy, and to advance the prospective randomized controlled trials, in order to establish a patient-centered, evidence-based new paradigm of precision immunosuppressive therapy and effectively improve the reproductive outcomes of patients with RSA.

Key words: Abortion, habitual, Immunosuppressive agents, Immunotherapy, Biological factors, Precise treatment