TNF- α -positive patients with recurrent pregnancy loss: The etiology and management

Abstract

BACKGROUND:

Elevated levels of tumor necrosis factor-alpha (TNF- $\alpha$ ) have been associated with adverse pregnancy outcomes, specifically recurrent pregnancy loss (RPL). These elevated levels may be associated with the presence of autoantibodies. Although TNF- $\alpha$ inhibitors have shown promise in improving pregnancy rates, further research is needed to comprehend their impact and mechanisms in RPL patients.

OBJECTIVE:

This study aims to investigate the association between elevated TNF- $\alpha$ levels and autoantibodies in RPL patients, as well as evaluate the effect of TNF- $\alpha$ inhibition on pregnancy outcomes.

METHODS:

A total of 249 RPL patients were included in this study. Serum levels of TNF- $\alpha$ , autoantibodies, and complement were measured and monitored. Among these patients, 138 tested positive for TNF- $\alpha$ , while 111 tested negative. The medical records of these patients were retrospectively evaluated. Additionally, 102 patients with elevated TNF- $\alpha$ levels were treated with TNF- $\alpha$ inhibitors, and their pregnancy outcomes were assessed.

RESULTS:

TNF- $\alpha$ -positive RPL patients had higher levels of complement C1q, anti-cardiolipin (ACL)-IgA, ACL-IgM ,ACL-IgG, thyroglobulin antibody, and Anti-phosphatidylserine/prothrombin IgM antibody, as well as a higher positive rate of antinuclear antibodies compared to TNF- $\alpha$ -negative patients (23.19% vs. 12.6%, $P<$ 0.05). Conversely, complement C3 were lower in TNF- $\alpha$ -positive patients ( $t$ test, $P<$ 0.05). The use of TNF- $\alpha$ inhibitors led to a reduction in the early abortion rate (13.7% vs. 44.4%, $P<$ 0.001) and an improvement in term delivery rate (52.0% vs. 27.8%, $P=$ 0.012). Furthermore, patients who used TNF- $\alpha$ inhibitors before 5 weeks of pregnancy had a lower early abortion rate (7.7% vs. 24.3%, $P=$ 0.033) and a higher term delivery rate (69.2% vs. 48.6%, $P=$ 0.033).

CONCLUSION:

TNF- $\alpha$ plays a role in the occurrence and development of RPL, and its expression is closely associated with autoantibodies and complements. TNF- $\alpha$ inhibitors increase the term delivery rate in TNF- $\alpha$ -positive RPL patients, and their use before 5 weeks of pregnancy may more beneficial.