Tumor necrosis factor inhibitors as therapeutic agents for recurrent spontaneous abortion (Review)

Recurrent spontaneous abortion (RSA) is a troublesome pregnancy disorder that manifests as sequential early pregnancy losses; its causes are diverse and complex. Among the known possible causes of RSA, the development of an immune disorder in response to the embryo appears to be the most pronounced. The imbalance between immune rejection and immune tolerance contributes to pregnancy loss in females with RSA, wherein the abnormal ratio of T helper (Th)1 cell‑related cytokines [predominantly tumor necrosis factor (TNF)‑α] and Th2 cell‑related cytokines is a strong risk factor for RSA. TNF‑α is a pro‑inflammatory cytokine and TNF inhibitors have been effective in the treatment of various autoimmune diseases, such as ankylosing spondylitis, and inflammatory diseases, such as ulcerative colitis. Based on their immunomodulatory properties, TNF inhibitors have been used in the treatment of RSA to reduce the immune rejection rate and improvement in pregnancy outcomes has been observed in females suffering from RSA who were treated with TNF inhibitors. The aim of the present review was to interpret the involvement of TNF‑α in the immunological disorder underlying RSA and summarize the clinical outcomes of TNF inhibitor treatment in patients with RSA.