Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. Recent studies show that spermatozoal DNA integrity is essential for normal fertilization and transmission of paternal genetic information to the offspring. Additionally, fertilization and embryo development depend on the sperm DNA structure (1,2). Generally, while fertile men have high levels of sperm with intact DNA structure associated with normal semen parameters, infertile men have decreased DNA integrity usually associated with abnormal semen parameters (3,4). However, this association is not unequivocal, as there have been several studies indicating that increased sperm DNA damage can occur in men with conventional sperm parameters within normal reference ranges (3,5,6). Increased sperm DNA damage is defined as the percentage by which the number of cells with defects in protamination of DNA structure in the evaluated sperm cells is calculated and expressed as the sperm DNA fragmentation index (DFI) (3). It is generally accepted that there is a significant negative correlation particularly between the abnormal sperm morphology percentage and DFI (3,6). In the present study, the authors evaluated the diagnostic importance and the clinical significance of sperm DFI tests in infertile males with different clinical conditions (7). Since varicocele is one of the most common causes of male infertility, the relationship between varicocele, sperm DNA integrity and abnormal DFI was evaluated in the study. It was reported that 11.7% of infertile males with normal semen analyses were also detected to have clinical varicocele in previous studies (8,9). The main cause of male infertility due to varicocele is oxidative stress and increased DFI (10,11). As the authors of the study have noted, recent meta-analysis showed that varicocelectomy improved sperm DNA integrity, and the mean difference of sperm DFI was reported to be approximately 3.37% (7,9). However, Agarwal et al. recommended surgery in cases of elevated sperm DFI tests in grade 2 and grade 3 with normal sperm parameters and in grade 1 cases with borderline or abnormal seminal parameters (7). According to international guidelines, impaired seminal parameters are already indicated for operation regardless of varicocele grade (12,13). Therefore, we conclude that, in addition to the authors’ suggestion, sperm DFI tests should be recommended to determine varicocelectomy in patients with normal seminal parameters regardless of varicocele grade and in cases of previous ART failure. Increased DFI is expected in advanced varicocele cases such as grade 3 with abnormal seminal parameters. However, evaluation of DFI tests in grade 1 varicocele cases with normal seminal parameters will contribute to the clinical use of these tests. Effects on natural pregnancy and ART outcomes of DNA fragmentation are also discussed in this study. It has been reported that high sperm DFI has been associated with failure to achieve natural pregnancy, poor ART outcomes, and high risk of miscarriage (14,15). There are several studies about sperm DNA damage and its association with impaired fertilization, suboptimal embryo quality, delayed blastocyst formation, reduced pregnancy rates, and increased abortion rate, not only with natural conception but also after IUI/IVF/ICSI treatment (2,7,14,15). In a meta-analysis involving 3,106 couples, sperm DNA damage was associated with a low pregnancy rate in IVF, but no difference in ICSI (16). In the same study, a close Commentary