BACKGROUND:Many factors have been implicated in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). The current study was conducted to determine the possible role of antioxidant status and tumor necrosis factor-alpha (TNF-alpha) in URSA. METHODS:Reduced glutathione (GSH), glutathione reductase (GSH-R), glutathione peroxidase (GSH-PX), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), malondialdehyde (MDA) and TNF-alpha were assayed in women suffering unexplained first-trimester abortions. Two groups were included, the first represented by 24 women with URSA (number of abortions 3-5) and the second included 16 women with URSA (number of abortions >5). The control group included 20 women within their first trimester of pregnancy and 20 non-pregnant healthy females within their follicular phase. RESULTS:We observed that the antioxidant levels measured were significantly lower in URSA groups than in the control group (p<0.05 for each comparison). Higher TNF-alpha, MDA and NO production were detected in URSA groups compared to controls (p<0.05 for each comparison). URSA 3-5 was associated with significantly higher levels of antioxidants and lower levels of TNF-alpha compared to levels in URSA >5. CONCLUSIONS:Impaired antioxidant defense and an increase in oxidative reactive species may be responsible for recurrent abortion due to possible damage produced by their generation. In addition, the level of TNF-alpha apparently contributes to the pathogenesis of URSA.