Role of TNF superfamily members lymphotoxin-α, sCD40L, and TNF-α in endometriosis-related infertility

Introduction: TNF-α, LT-α, and sCD40L belong to the TNF superfamily and play a pivotal role in chronic inflammatory disease. Yet, these soluble molecules are largely unexplored in endometriosis cases with infertility. The present study aimed to evaluate serum and peritoneal fluid levels of these molecules and correlate its level to the endometriosis severity. Methods: Peripheral blood and peritoneal fluid samples were obtained from 87 infertility cases who underwent laparoscopy, consisting of 44 endometriotic women and 43 non-endometriotic women. The levels of TNF-α, LT-α, and sCD40L were determined using ELISA. Results: Serum and peritoneal TNF-α levels were significantly elevated in the endometriosis group compared to the control group ( p = 0.028; p = 0.027), but not the sCD40L and LT-α level. Serum and peritoneal TNF-α levels were significantly different between late-endometriosis (stage III or IV) compared to the control group ( p = 0.026, p = 0.041, respectively). Moreover, the serum LT-α level was significantly higher in late-endometriosis cases compared to the early-endometriosis (stage I or II) cases ( p = 0.03) and showed a positive correlation with endometriosis rASRM score ( p = 0.001). ROC curve analysis showed a significant diagnostic value of serum LT-α in differentiating the late cases to the early endometriosis patients (AUC = 0.751, p = 0.007). A negative correlation between LT-α and total Endometriosis Fertility Index (EFI) score was also observed ( p = 0.012). Conclusion: Severe endometriosis and lower EFI score are associated with higher serum LT-α level. Serum LT-α is a potential staging biomarker among endometriosis cases. Serum and peritoneal TNF-α levels were elevated in women with severe endometriosis among infertility cases. Further study should address the role and predictive value of LT-α in endometriosis-related infertility.