Comparison of Methods for Assessment of Sperm DNA Damage (Fragmentation) and Implications for the Assisted Reproductive Technologies

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Few topics have been more misunderstood than sperm DNA damage. Sperm is particularly vulnerable to DNA damage as the mature sperm does not have any repair mechanism and also lacks antioxidant defense enzymes. The damage appears to occur in two steps: Primary damage of the sperm DNA occurs in the testicle in the form of endogenous “nicks,” poor protamination, or initiation of apoptosis, and in the epididymis as deficient disulfide cross-linking. The initial damage makes the sperm DNA vulnerable to secondary damage when it has left the testicle. Secondary damage is largely caused by oxidative stress, but may also be caused by spontaneous degradation due to the presence of oxygen free radicals and water. Sperm DNA damage can be detected by the three methods Comet, TUNEL, and SCSA. Previous controversy regarding the importance of sperm DNA damage for reproductive outcome appears to be initiated by the incorrect assumption that sperm DNA damage would impact IVF and ICSI treatments to the same extent as observed for natural intercourse and IUI treatments. On the contrary, sperm DNA damage is a dynamic parameter where the extent of secondary damage depends on the “length” of the sperm’s “journey” to the oocyte. Less secondary damage occurs in IVF and especially ICSI, and the reduction in success rates for these two types of treatment is therefore less than for IUI or natural intercourse. In cases with a high level of sperm DNA damage, an effective solution could be to perform ICSI treatment by use of testicular sperm as this will minimize the amount of secondary sperm DNA damage. Before we decide to undertake this invasive procedure, it should be considered that sperm DNA damage and incorrect repair of this damage by the oocyte appear to be the main cause of mutations in the newborn. Recent research shows that approximately 94 % all mutations come from the male and that diseases in the child such as autism, bipolar disorder, schizophrenia, and childhood cancers are more prevalent with male age. Increasing male age is not the only factor, which appears to increase the level of sperm DNA damage. Factors such as smoking, overweight, diabetes, and reduced level of vitamins and/or antioxidants may be responsible for the occurrence of DNA damage. Correction of such factors is an alternative and less invasive procedure, which may lead to higher treatment success rates, reduced risk for mutations in the newborn, as well as a general improvement in male health.