Descriptive analysis of immunological abnormalities in recurrent reproductive failure and therapeutical outcomes

Abstract

INTRODUCTION Reproductive immunology has advanced significantly, recognizing the immune system as crucial in pregnancy development and facilitating the identification of abnormalities causing recurrent reproductive failure, as well as proposing targeted treatments for these patients. METHODS This is a descriptive, observational, and retrospective study conducted at the Reproductive Immunology Unit of the Hospital Clínico San Carlos in Madrid. Clinical and analytical data were analyzed for patients diagnosed with recurrent reproductive failure between 2019 and 2023. Data on treatments received as prophylaxis for pregnancy loss and their success rates were also collected. Finally, a comparative study of the two major subgroups in the cohort was performed. RESULTS A total of 277 patients were included. The most prevalent diagnosis was recurrent miscarriage (64.2%), followed by recurrent implantation failure (25.2%). Immunological and/or vascular abnormalities were detected in 88.8% of patients. The most prevalent immunological abnormality was the expansion of cytotoxic natural killer cells (49.5%), followed by HLA-C-KIR mismatch (39.1%) and the presence of antiphospholipid antibodies (38.5%). The comparative study between the recurrent miscarriage and the recurrent implantation failure subgroups revealed statistically significant differences regarding the presence of antinuclear antibodies (15.4% vs. 28.3%, p=0.03) and vitamin D deficiency (37.2 vs 60.0%, p=0.01). The most commonly used medications were low-dose acetylsalicylic acid, low-molecular-weight heparin, hydroxychloroquine, and/or prednisone, with an overall success rate of 97.3%. Neither moderate nor severe side effects were reported. CONCLUSIONS Immunological studies to identify causes of recurrent reproductive failure are highly useful in cases where other etiologies have been excluded. Targeted therapies for addressing these abnormalities have demonstrated significant effectiveness.