Sperm chromatin damage impairs human fertility

Abstract Objective: To examine the relationship between sperm chromatin defects, evaluated by the flow cytometric (FCM) sperm chromatin structure assay (SCSA), and the probability of a pregnancy in a menstrual cycle (fecundability). Design: Follow-up study. Setting: The Section of Toxicology and Biomedical Sciences, ENEA Casaccia, Rome, Italy, and the Department of Occupational Medicine, Aarhus University Hospital, Aarhus, Denmark. Patient(s): Two hundred fifteen Danish first pregnancy planners with no previous knowledge of their fertility capability. Intervention(s): None. Main Outcome Measure(s): Semen samples were collected at enrollment to measure semen volume, sperm concentration, motility, and morphology (by microscopy), as well as chromatin susceptibility to in situ, acid-induced partial denaturation by the FCM SCSA. Time to pregnancy was evaluated during a 2-year follow-up period. Demographic, medical, reproductive, occupational, and lifestyle data were collected by questionnaire. Fecundability was correlated with SCSA-derived parameters. Result(s): Fecundability declines as a function of the percentage of sperm with abnormal chromatin and becomes small when aberrant cells are >40%. Conclusion(s): Optimal sperm chromatin packaging seems necessary for full expression of the male fertility potential. The SCSA emerged as a predictor of the probability to conceive in this population-based study.