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

Article type: Research Article

Authors: Cai, Zhuhua^{a; b; 1} | Guo, Xueke^{b; 1} | Zheng, Ge^c | Xiang, Junmiao^b | Liu, Lingyun^d | Lin, Dongmei^b | Deng, Xiaohui^{a; *}

Affiliations: [a] Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Qilu Hospital of Shandong University, Jinan, China | [b] Department of Obstetrics and Gynecology, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China | [c] Pediatric Department, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China | [d] Central Laboratory, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

Correspondence: [*] Corresponding author: Xiaohui Deng, Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 27 Shanda South Road, Licheng District, Jinan 250012, China. Tel.: +86 18560082026; Fax: +86 577 6586586; E-mail: [email protected].

Note: [1] Zhuhua Cai and Xueke Guo contributed equally to this work.

Abstract: BACKGROUND: Elevated levels of tumor necrosis factor-alpha (TNF-α) 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-α 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-α levels and autoantibodies in RPL patients, as well as evaluate the effect of TNF-α inhibition on pregnancy outcomes. METHODS: A total of 249 RPL patients were included in this study. Serum levels of TNF-α, autoantibodies, and complement were measured and monitored. Among these patients, 138 tested positive for TNF-α, while 111 tested negative. The medical records of these patients were retrospectively evaluated. Additionally, 102 patients with elevated TNF-α levels were treated with TNF-α inhibitors, and their pregnancy outcomes were assessed. RESULTS:TNF-α-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-α-negative patients (23.19% vs. 12.6%, P< 0.05). Conversely, complement C3 were lower in TNF-α-positive patients (t test, P< 0.05). The use of TNF-α 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-α 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-α plays a role in the occurrence and development of RPL, and its expression is closely associated with autoantibodies and complements. TNF-α inhibitors increase the term delivery rate in TNF-α-positive RPL patients, and their use before 5 weeks of pregnancy may more beneficial.

Keywords: Antinuclear antibodies, anti-phospholipid antibodies, estrogen, human chorionic gonadotropin, pregnancy, pregnancy outcome, tumor necrosis factor

DOI: 10.3233/THC-240757

Journal: Technology and Health Care, vol. 32, no. 6, pp. 4581-4591, 2024