Immunotherapy for recurrent pregnancy loss: a reappraisal

Recurrent pregnancy loss (RPL) is frequently encountered in the outpatient setting. Despite extensive investigation, up to 50% of patients will be diagnosed with idiopathic RPL, for which no effective treatment exists. While the immune system is intricately involved in the initiation and maintenance of pregnancy, there are no validated diagnostic tests to confirm immune-mediated pregnancy loss. Therefore, drugs aiming to modulate or suppress the immune system are often used on speculation with limited scientific evidence. As the literature is heterogeneous and difficult to assimilate, we sought to provide the reader with an objective and comprehensive review of each type of treatment (progesterone, aspirin, low-molecular-weight heparin, granulocyte colony-stimulating factor, human chorionic gonadotropin, corticosteroids, Intralipids, and intravenous immunoglobulins), highlighting the possible mechanisms of action, potential efficacy or futility, and risks associated. This review aims to summarize current knowledge on the topic, provide a clinical guide for decision-making, and identify knowledge gaps required to harmonize practices and develop guidelines for suspected immune-mediated RPL management.