The price and value of sperm DNA fragmentation tests

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. Drs. Fraczek and Kurpisz, in their insightful commentary, highlighted the pitfalls of the current sperm DNA fragmentation (SDF) testing (1). These authors remarked that the association between SDF and clinical outcome of assisted reproduction is not without controversy in the literature. An interesting study cited by these authors proposes the predictive values of sperm vitality on SDF (2) and deserves further discussion in our response. Semen analysis has been the cornerstone of male fertility evaluation despite its poor predictive value on fertility potential. There is an extensive overlap in conventional semen parameter result between fertile and infertile men (3). Since the release of the first edition of WHO guidelines for semen analysis over three decades ago (4), SDF testing is becoming an important tool for fertility specialists, thanks to the great large number of reports from all over the world. The SDF testing was transformed from a research tool in 1980s to a diagnostic test readily available in clinical andrology laboratories and in vitro fertilization (IVF) clinics across the world in the 21st century. Even though the Practice Committee of the American Society of Reproductive Medicine (ASRM) recognized the significance of abnormal SDF on the results of natural pregnancy, intrauterine insemination (IUI), IVF, and intracytoplasmic sperm injection (ICSI) in 2015; its routine use in predicting assisted reproductive outcomes is not recommended (5). Strong correlation between SDF and natural pregnancy is best illustrated by the Danish First Pregnancy Planner Study (6) and the Longitudinal Investigation of Fertility and the Environment (LIFE) Study (7) which unmistakably demonstrated the negative impact of SDF on time to pregnancy. Couples with a sperm DNA fragmentation index (DFI) of less than 40% by Sperm Chromatin Structure Assay (SCSA) were shown to have 10 times higher probability in achieving natural pregnancy (6). Likewise, an OR of 9.9 (95% CI, 2.37–41.51) was reported in a study correlating SCSA DFI greater than 30% with decreased pregnancy and delivery rates after IUI (8). Although the magnitude of OR seems less impressive, significant OR of around 1.5 on pregnancy rates by IVF and ICSI has been consistently reported (9). More importantly, higher live birth rates after IVF [relative risk (RR) =1.27; 95% CI, 1.05–1.52] and ICSI (RR =1.11; 95% CI, 1.00–1.23) was reported in a recent systematic review and metaanalysis (10). The complexity of human reproductive system with involvement of multiple confounding factors from both male and female partners precludes a simple straightforward test in predicting fertility potential. We feel that it is less important to compare which test is better over the other in prediction of natural and assisted conception; rather, it is essential to recognize the distinct and unique nature of SDF tests in assessing the genetic material of male gamete which contributes half of DNA contents of the offspring. We believe that the SDF tests and semen analysis, along with other sperm function tests, should be complementary to each other in providing the best information to fertility specialists and infertile couples. Controversies do exist about the use of SDF test as is the case for almost all other clinical tests in the field of medicine, but the expanding evidence in support of clinical use of SDF tests cannot be Editorial