Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha in human spermatozoa: an in vitro model

Objective: To examine the toxic effects of tumor necrosis factor alpha (TNF-alpha) on ejaculated spermatozoa and evaluate the ability of infliximab to reverse these effects. Design: Prospective controlled study. Setting: Cleveland Clinic Foundation, Cleveland, Ohio. Patient(s): Thirty-one healthy sperm donors. Intervention(s): Exposure of human spermatozoa to varying concentrations of TNF-a (100, 300, 400, 500 pg/mL, and 2.5 mu g/mL) and infliximab (400 mu g/mL). Main Outcome Measure(s): Sperm motility, functional integrity of plasma membrane, and DNA fragmentation. Result(s): Spermatozoa quality declined following incubation with TNF-a in a dose-dependent and time-dependent manner. Sperm motility and membrane integrity were higher in the samples incubated with TNF-a plus infliximab than in the samples treated with TNF-a only. These parameters improved significantly and were comparable with both controls and sperm incubated with infliximab alone. Similarly, the percentage of spermatozoa with DNA fragmentation improved significantly following incubation with TNF-a plus infliximab and again was comparable with both controls and sperm incubated with infliximab alone. Conclusion(s): Spermatozoa may be exposed to abnormal levels of TNF-a in the male reproductive tract or during their passage into the female reproductive tract (in cases of endometriosis). Exposing spermatozoa, to pathological concentrations of TNF-a can result in significant loss of their functional and genomic integrity. Infliximab could potentially be used to help treat female infertility caused by endometriosis in those with elevated levels of TNF-alpha in their peritoneal fluid. (c) 2005 by American Society for Reproductive Medicine.