Year: 2025
Type: article
Abstract: Recurrent miscarriage (RSA) is one of the most common complications during pregnancy, defined as two or more consecutive pregnancy losses with the same sexual partner (some recent guidelines and studies have shifted the threshold to two occurrences). This condition causes significant physical and psychological trauma to patients and their families. The etiology of RSA is complex, involving multiple factors such as genetics, anatomy, endocrine, immune, pre-thrombotic state, infections, male factors, and environmental influences. Approximately 50% of cases remain etiologically unexplained, termed recurrent miscarriage of unknown cause. Recent advancements in reproductive medicine, immunology, and molecular genetics have deepened our understanding of RSA etiology, particularly in immune factors and pre-thrombotic state research. This article systematically reviews known and potential causes of RSA, including chromosomal abnormalities in embryos, anatomical abnormalities in the maternal uterus (such as uterine septum and intrauterine adhesions), endocrine disorders (e.g., thyroid dysfunction, hyperprolactinemia, insulin resistance), autoimmune diseases (e.g., antiphospholipid syndrome, systemic lupus erythematosus), alloimmune disorders, acquired and hereditary pre-thrombotic states, chronic endometritis, as well as lifestyle and environmental factors. This study provides a comprehensive review of individualized and stratified treatment strategies for different etiologies of recurrent spontaneous abortion (RSA), including preconception counseling and risk assessment, genetic interventions (such as preimplantation genetic testing), surgical corrections (e.g., hysteroscopic septum resection), endocrine modulation (including thyroid hormone replacement and metformin therapy), anticoagulation and immunomodulatory treatments targeting immune factors (such as low molecular weight heparin, glucocorticoids, hydroxychloroquine, active lymphocyte immunization, and intravenous immunoglobulin), as well as anticoagulation for pre-thrombotic states. The article further discusses current challenges in RSA management, such as controversies surrounding the management of idiopathic RSA, and outlines future research directions including microbiome studies, multi-omics research on maternal-fetal immune microenvironments, and exploration of novel biomarkers. It emphasizes that systematic and comprehensive etiological screening, followed by precision and individualized multidisciplinary collaborative management, is crucial for improving pregnancy outcomes in RSA patients.
Author: Chen Sun
Institution: Changsha Medical University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7118596148