A tumor necrosis factor-α inhibitor reduces the embryotoxic effects of endometriotic peritoneal fluid

Objective: To determine whether a tumor necrosis factor-alpha (TNF-alpha) inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women with endometriosis. Design: Experimental clinical study. Setting: University hospital. Patient(s): Twelve women with chocolate cysts and 12 control women without endometriosis. Intervention(s): None. Main Outcome Measure(s): We collected the PF from patients with chocolate cysts (CH-PF) and patients without endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies, development and apoptosis were evaluated in two-cell stage mouse embryos after incubation with CH-PF and N-PF, with or without a TNF-alpha inhibitor. Result(s): Wefound thatCH-PF significantly decreased the rate of blastocyst development and increased the percentage of apoptotic cells in the embryos. Cytokine assays showed that the concentrations of several cytokines, including TNF-alpha, were higher in embryos incubated with CH-PF than in those incubated with N-PF. Furthermore, the treatment of embryos with TNF-alpha retarded development and induced apoptosis. Important, adalimumab, a TNF-alpha inhibitor, effectively abrogated the embryotoxicity that was induced by CH-PF. Conclusion(s): These data collectively highlight the crucial role of TNF-a in CH-PF-induced embryotoxicity and suggest that TNF-alpha inhibitors may be potential therapeutic agents for treating endometriosis-induced infertility. (C) 2013 by American Society for Reproductive Medicine.