OBJECTIVE: Ribavirin (RIB) plus pegylated interferon (PEG-IFN) is the standard combination treatment for hepatitis C. Based on male animal studies, couple contraception is recommended during and for 6 to 7 months after treatment. To date, there are no human published data to support this practice. This study describes for the first time the side effects of HCV combination treatment on human spermatozoa.DESIGN: Case report study.MATERIALS AND METHODS: A 37-old man, HCV-infected, performed 7 sperm samples before (period 1), 4 during and within 7 months after treatment by RIB (Rebetol™, 1000mg/day) and PEG-IFN (Viraferon™, 115.2 ug /week) (period 2) and finally 7 more than 7 months following the end of treatment (period 3). The patient gave his informed consent. Semen analysis was performed according to WHO criteria. Sperm Chromatin Structure assay (SCSA) was done according Evenson and Jost (2000)with minor modifications. Results of SCSA were expressed as DNA fragmentation index (DFI) and highly DNA stainable cells (HDS). Moreover, DNA fragmentation was measured by TUNEL assay. Wilcoxon test and analysis of variance were used for statistical analysis.RESULTS: Between period 1 and period 2, a significant decrease of the percentage of progressive motile spermatozoa (27.1 ± 6.4 vs 18.2 ± 7.0, p <0.05) and of the total number of progressive motile spermatozoa in the ejaculate (82.5 ± 40.1 vs 27.6 ± 29.2, p <0.05) were observed. The round cell/spermatozoa ratio increased very markedly from 2.6 ± 1.4% before treatment to 23.6 ± 13.0% during period 2 (p <0.05). Sperm DNA fragmentation (TUNEL assay) was highest at 7 months of treatment (36.8%) and remained increased 1 month after treatment end. It was noteworthy that the DFI (SCSA), which defines abnormal chromatin structure, increased very markedly from 14.5% before treatment to 69.2% at 7 months of treatment and remained increased until 8 months after the end of treatment (45.5%). The DFI returned to pretreatment values 12 months after.CONCLUSIONS: This study demonstrates, that in man RIB plus PEG-IFN treatment can have marked effects on semen parameters and chromatin sperm integrity. These findings are of paramount interest for patient counseling. Currently, contraception is recommended during and 6-7 months after the end of Ribavirin treatment in women or men. Our study argues for a more prolonged contraception period, as 8 months after discontinuation sperm chromatin values had not returned to pretreatment status. OBJECTIVE: Ribavirin (RIB) plus pegylated interferon (PEG-IFN) is the standard combination treatment for hepatitis C. Based on male animal studies, couple contraception is recommended during and for 6 to 7 months after treatment. To date, there are no human published data to support this practice. This study describes for the first time the side effects of HCV combination treatment on human spermatozoa. DESIGN: Case report study. MATERIALS AND METHODS: A 37-old man, HCV-infected, performed 7 sperm samples before (period 1), 4 during and within 7 months after treatment by RIB (Rebetol™, 1000mg/day) and PEG-IFN (Viraferon™, 115.2 ug /week) (period 2) and finally 7 more than 7 months following the end of treatment (period 3). The patient gave his informed consent. Semen analysis was performed according to WHO criteria. Sperm Chromatin Structure assay (SCSA) was done according Evenson and Jost (2000)with minor modifications. Results of SCSA were expressed as DNA fragmentation index (DFI) and highly DNA stainable cells (HDS). Moreover, DNA fragmentation was measured by TUNEL assay. Wilcoxon test and analysis of variance were used for statistical analysis. RESULTS: Between period 1 and period 2, a significant decrease of the percentage of progressive motile spermatozoa (27.1 ± 6.4 vs 18.2 ± 7.0, p <0.05) and of the total number of progressive motile spermatozoa in the ejaculate (82.5 ± 40.1 vs 27.6 ± 29.2, p <0.05) were observed. The round cell/spermatozoa ratio increased very markedly from 2.6 ± 1.4% before treatment to 23.6 ± 13.0% during period 2 (p <0.05). Sperm DNA fragmentation (TUNEL assay) was highest at 7 months of treatment (36.8%) and remained increased 1 month after treatment end. It was noteworthy that the DFI (SCSA), which defines abnormal chromatin structure, increased very markedly from 14.5% before treatment to 69.2% at 7 months of treatment and remained increased until 8 months after the end of treatment (45.5%). The DFI returned to pretreatment values 12 months after. CONCLUSIONS: This study demonstrates, that in man RIB plus PEG-IFN treatment can have marked effects on semen parameters and chromatin sperm integrity. These findings are of paramount interest for patient counseling. Currently, contraception is recommended during and 6-7 months after the end of Ribavirin treatment in women or men. Our study argues for a more prolonged contraception period, as 8 months after discontinuation sperm chromatin values had not returned to pretreatment status.