Sperm DNA fragmentation testing is on the right track

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. Dr. Oehninger’s elegant editorial dwelled on several unresolved i s sues in the context of sperm DNA fragmentation (SDF) (1). Indeed, we appreciate and agree with his comments that development of better diagnostic methodology, evaluation of true functional consequences and understanding of oocyte repair capacity are important areas of research. It is widely believed that SDF is one of the major causes of male infertility and that DNA fragmentation can be caused by a variety of factors such as infection, chemotherapy, radiotherapy, smoking, drug use, or advanced age (2). Furthermore, SDF is linked to impaired fertilization, poor embryo quality, increased spontaneous abortion rates and reduced pregnancy rates after assisted reproduction (3). Dr. Oehninger’s comments about the “limited number of studies showing that SDF levels can predict the likelihood of natural pregnancy and that higher SDF levels are associated with lower intrauterine insemination (IUI) pregnancy rates, and with lower embryo quality and pregnancy rates in the in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) scenario” are valid but deserve to be viewed in a correct perspective. Although only a few studies reported the role of SDF in natural pregnancy, they have consistently demonstrated a significant odds ratio (OR). A meta-analysis by Zini involving 3 studies and 616 couples, showed that high SDF as measured by sperm chromatin structure assay (SCSA) was associated with a failure to achieve natural pregnancy with an OR of 7.01 (4). The Danish first pregnancy planners study clearly illustrated that the time-to-pregnancy increased with sperm DNA fragmentation index (DFI) and men became infertile when the DFI exceeded 30% in an unselected population (5). The role of SDF in fertility assessment was further supported by recent data where the authors reported a sensitivity of 80.8% and specificity of 86.1% in predicting pregnancy with a cutoff of 26.1% by sperm chromatin dispersion (SCD) method (6). More importantly, the SDF testing showed a predictive value independent of conventional semen parameters (7). The effect of SDF on assisted reproductive technologies (ART) outcomes were widely reported previously and continued to be supported by upcoming data. Lower pregnancy rate with IUI was correlated with higher DFI and there was a significant difference in DFI between males with successful and unsuccessful IUI outcomes, as reported in a recent study (8). There is even more evidence signifying the deleterious effect of SDF on embryo quality. Simon et al. demonstrated the paternal influence of SDF on early embryonic development and implantation (9). The tremendous number of studies on the effect of SDF on IVF and ICSI outcomes were summarized in a review and meta-analysis (10,11). An analysis of a total of 8,068 treatment cycles revealed a significantly negative effect of SDF on clinical pregnancy in both IVF and ICSI (11). Despite all the current hurdles in clinical application of SDF testing, the predictive value of SDF in both natural pregnancy and ART outcomes has been consistently supported by utilizing various testing methods in different patient groups. Therefore it is critical that we should not overlook the expanding evidence on SDF testing. Another point raised by Dr. Oehninger is that SDF tests Editorial