More good than harm should be expected when Testi-ICSI is applied to oligozoospermic men with post-testicular sperm DNA fragmentation

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. We read with interest the commentary by Dr. Paul Turek (1) contextualizing the use of sperm DNA fragmentation (SDF) testing for male infertility in response to the recently published practice recommendations for SDF testing based on clinical scenarios by Agarwal et al. (2). We certainly concur with the author regarding the limitations of conventional semen analysis parameters as surrogate measures of male fertility potential (3,4) and that SDF testing is one of the most relevant advancements to the andrological evaluation of male infertility (5,6). Moreover, Dr. Turek critically analyzed the use of testicular in preference over ejaculated sperm for intracytoplasmic sperm injection (ICSI), which has been presented by Agarwal et al. as an alternative to overcome infertility in men with elevated levels of SDF undergoing ICSI (2). In his commentary, the author caution against the indiscriminate use of testicular sperm for ICSI (TestiICSI) and rationalize his arguments based on the following premises: (I) there is no indication of Testi-ICSI in cases of failed IVF/ICSI cycles with ejaculated sperm normal or untested SDF; (II) the use of Testi-ICSI in cases of severe oligozoospermia without evidence of sperm DNA damage lacks supportive evidence; and (III) testicular sperm has higher chromosomal aneuploidy rates than ejaculated sperm. Along these lines, we wish to add some comments that may help readers better understand the matter concerned. Foremost among all is perhaps the fact that the available evidence favoring the use of Testi-ICSI seems to be limited to men with elevated SDF rates in the neat ejaculate. In this scenario, others and we have shown that the rates of SDF are markedly lower in testicular sperm than ejaculated sperm (7-9). We have studied oligozoospermic (5–15 million spermatozoa/mL) men presenting with persistent high SDF (>30%) despite continuous use of oral antioxidant therapy for 3 months and found that SDF rates were fivefold lower in the testis (8.3%±5.3%) than in the semen (40.7%±9.9%; P<0.001) (7). In our study, SDF was assessed using the sperm chromatin dispersion (SCD) method combining a dual fluorescent probe to target both the DNA and proteins that allow discrimination between spermatozoa and other cell elements in testicular suspensions (10). The biological plausibility of reduced SDF in the testis relies on three essential aspects. First, chromatin compaction is still ongoing during epididymal transit. Second, excessive reactive oxygen species (ROS) can be generated in the epithelial cells of epididymis under physicochemical stressors such as high temperature and environmental conditions (11-13). Lastly, certain endonucleases can cleave DNA of mature live sperm (14). As a result, sperm DNA damage may ensue through different pathways, including hydroxyl radical, nitric oxide, and activation of sperm caspases and endonucleases, thus explaining the positivity for SDF in live ejaculated sperm of infertile men (15). This oxidativeinduced damage to the sperm chromatin can be potentially avoided in ICSI candidates provided the epididymis is Editorial