Comparison of strategies to reduce sperm DNA fragmentation in couples undergoing ICSI

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. We read with interest the commentary by Drs. Jan Tesarik and Maribel Galán-Lázaro (1) regarding the recently published practice recommendations for sperm DNA fragmentation (SDF) testing based on clinical scenarios by Agarwal et al. (2). Drs. Tesarik and Galán-Lázaro advocate the use of SDF testing in all cases of fertility problems based on the potentially dangerous implications of damaged DNA to both natural and assisted conception. Notwithstanding, the authors recognize that certain clinical scenarios pose a higher risk to the couple, and therefore contributed an algorithm to guide clinicians in ordering the test and managing affected men (depicted in Table 1 and Figure 1 in their article). As the reader will see by examining their proposed algorithm, two techniques for deselecting sperm with damaged DNA, namely, motile sperm organelle morphology examination (MSOME) and physiologic ICSI (PICSI) using hyaluronic acid-selected spermatozoa, received a significant amount of attention. In this article, we discuss the existing laboratory strategies to remove sperm with damaged DNA for use in association with intracytoplasmic sperm injection (ICSI). To our knowledge, there is only one study that compared interventions aimed at selecting sperm populations with better DNA integrity for use with ICSI (3). In this report, Bradley et al. retrospectively evaluated 448 ICSI cycles from couples whose male partners had high levels of SDF. Sperm injections were performed with either ejaculated sperm or testicular sperm. In the ejaculated sperm group, the authors applied interventions to reduce SDF including IMSI, PICSI, and frequent ejaculation, and compared outcomes with a control group of ‘no intervention’. They also compared the results of ICSI using ejaculated sperm with and without intervention to testicular sperm (Testi-ICSI), and found higher live birth rates (P<0.05) with Testi-ICSI (49.8%) than IMSI (28.7%) and PICSI (38.3%). The lowest live birth rates (24.2%) were achieved when no intervention was carried out to select sperm with intact DNA (P=0.020). Notably, the utilization rate, calculated as the proportion of embryos available for transfer or cryopreservation per zygotes, was significantly higher among men subjected to ICSI with testicular sperm than ejaculated sperm (54.7% vs. 43.8%). This study adds to the existing evidence suggesting an advantage of testicular sperm in preference over ejaculated sperm for ICSI to selected men with confirmed high SDF in semen. Unfortunately, this study did not provide data on the magnitude of SDF reduction after each intervention modality. However, studies examining the effectiveness of laboratory strategies to reduce SDF do exist. Shortening the ejaculatory abstinence, repeated ejaculation, and density centrifugation, alone or combined, have shown to provide a reduction in the proportion of sperm with damaged DNA ranging from 22% to 47% (4-7). Likewise, swim-up has yielded a reduction of about 35% in the proportion of DNA damaged sperm (7,8). On the contrary, techniques such as magnetic cell sorting (MACS), PICSI and IMSI have brought about conflicting results; while some studies have Editorial