AbstractBackgroundSperm DNA damage is a major cause of pre‐ and post‐implantation embryonic loss in humans. However, the factors that control how and when such DNA damage occurs in human sperm are poorly understood.MethodsHere, I review information relating to sperm DNA damage that can be obtained from the sperm chromosome assays described in the existing literature.Main findingsThe sperm chromosome assays, which consist of interspecific in vitro fertilization or intracytoplasmic sperm injection using murine oocytes and subsequent chromosome analysis, indicate that the proportion of sperm showing DNA damage is initially low and there are larger numbers of sperm with potential membrane and DNA damage that are induced after ejaculation and separation from the seminal plasma. Other assays that directly detect sperm DNA (e.g., TUNEL assays, Comet assays, and acridine orange test) are not able to distinguish and detect the initial and potential DNA damage. Furthermore, the positive values in these direct assays are influenced by the frequency of immotile sperm and amorphous sperm populations.ConclusionThe findings in the sperm chromosome assays show that further improvements in sperm preparation protocols may result in the reduction of sperm DNA damage, followed by more successful outcomes in infertility treatment.