Clinical usefulness of sperm DNA fragmentation testing

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. The search for the best biomarker for the diagnosis of male infertility is more evident in recent years as conventional semen analysis is not always an optimal predictor of male fertility. Since the advent of the intra-cytoplasmic sperm injection (ICSI) for male factor infertility, the pace of research related to sperm functional assays has slowed down. The haploid male gamete contributes fifty percent of the genome to the zygote, hence any perturbations at the genetic or molecular level of the spermatozoon may be reflected in the fertilized zygote, preimplantation embryo and resulting pregnancy. Chromatin organization and all its associated modifications, whether it concerns the DNA itself and/or the nuclear proteins, are critical for gene expression, cell division, and differentiation. Therefore, reproductive science researchers, as well as reproductive medicine specialists, have been keen to explore the causes of poor embryo quality, early miscarriages and unexplained infertility in relation to sperm quality. The last two decades have seen myriad of developments in the research related to oxidative stress and DNA fragmentation index (DFI) of male reproductive system, especially spermatozoa. The essential question being asked by many in the field is whether sperm DNA fragmentation analysis adds useful information which can change diagnosis, or in understanding the prognosis better. Numerous studies have shown that sperm DNA fragmentation is an important cause of male infertility (1). However, the current literature on the predictive values of sperm DNA quality evaluation and the outcomes of assisted reproductive technology is still controversial. The extensive compaction and remodelling of the chromatin yield a highly complicated package of DNA in the sperm head (2). DNA compaction and packaging is not an error free process. Any error during this step may also contribute to sperm DNA damage. Another potential etiology for sperm DNA damage includes abortive apoptosis and the exposure of spermatozoa to imbalance in ROS-antioxidant systems in post testicular environment (3). Even though there are many tests that have been developed and tested for the integrity of sperm DFI, currently four of them are widely used: the Comet assay, terminal deoxyuridine nick end labeling (TUNEL) assay, Sperm Chromatin Structure Assay (SCSA), and Sperm Chromatin Dispersion (SCD) assay (4). The Comet and TUNEL assays detect DNA strand breaks while SCSA and SCD measure chromatin integrity and the susceptibility of DNA to denaturation. As Agarwal et al. (5) nicely explain in their manuscript, we still do not understand the true nature of DFI and what it is that the each DNA test measures (5). Even though it has been widely accepted that the SDF tests prove to have less biological variability compared to conventional semen analysis results, there exists considerable inter-laboratory variability in test results. Another confusing area is the different threshold (Cut off) values for different SDF tests. Moreover the SDF tests can be affected by the clinical conditions of the patient such as Commentary