Sperm DNA Damage: Causes and Guidelines for Current Clinical Practice

Abstract

Infertility is a common health problem affecting approximately 15% of all couples. It is estimated that, in at least 50% of all cases, impairment of semen quality is a factor contributing to the problem of the couple. Furthermore, 10-15% of all infertility cases are ``unexplained''. Traditional sperm parameters concentration, motility, morphology were shown to have a poor predictive value, both in relation to fertility in vivo and in vitro. Thus, there is an urgent need of finding new sperm quality markers that can be used for the evaluation of the chance of a couple to conceive in a natural way, and also, if necessary, for the selection of the right assisted reproductive technique (ART). In this context, testing of sperm DNA integrity seems to be a potential candidate. The causes of sperm DNA damage are multi-factorial, including testicular and post-testicular, genetic and exposure-related mechanisms. For the assessment of sperm DNA damage, a number of different techniques is available. The results obtained by these methods are generally correlated, but, on the other hand, they seem to measure slightly different elements of sperm DNA integrity and they provide limited information on the nature of the lesions detected. So far, assessment of sperm DNA has proven to be the most powerful in predicting in vivo infertility, which means cases where the chance of pregnancy by natural conception or intrauterine insemination is close to zero. High percentage of sperms with DNA defects seems also to have a negative impact on the results of standard in vitro fertilisation (IVF), but not on that of intracytoplasmatic sperm injection (ICSI), even if the issue is debatable and under active scrutiny. Clinically applicable threshold values have been defined for one of the methods for assessment of sperm DNA integrity the sperm chromatin structure assay (SCSA) - but not yet for the other techniques. There is a need for standardisation of technology for these assays in the same way as it has been achieved for SCSA. Thus, well-designed studies should be carried out in order to define the clinical role of these new measures of sperm quality. This is important from the diagnostic as well as therapeutic point of view, since a more nuanced characterisation of sperm DNA defects will not only lead to an improved choice of the ART methods, but may also help in developing cause-related therapy of male subfertility. From the biological point of view, it needs to be investigated whether sperm DNA damage transmitted to the embryo by use of IVF and ICSI can be hazardous to the offspring, taking into account the wealth of animal data demonstrating the link between sperm DNA damage and abnormalities in embryo development.