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The argument for the use of testicular sperm instead of ejaculated sperm for infertility due to sperm DNA fragmentation (SDF) relies on several assumptions. When each assumption is examined, it becomes clear that the assumptions are either unproven, due to insufficient data, or just plain wrong. These assumptions are: 1) sperm DNA fragmentation assays are good diagnostic tests; 2) IVF/ICSI failed because of elevated SDF; and 3) testicular sperm will result in pregnancy or live birth when ejaculated sperm will not. It has been demonstrated that when comparing populations, SDF is greater in infertile than in fertile populations. In addition, SDF is negatively associated with pregnancy rates by IVF/ICSI with an odds ratio of 1.68 (1). However, these population associations are insufficient to rely of SDF assays to direct patient management. There are a multitude of SDF assays, some such as TUNEL, directly measure the presence of sperm DNA fragmentation, while others such as SCSA, alkaline COMET, and Sperm Chromatin Dispersion (SCD) only indirectly measure fragmentation. There remains poor standardization of techniques and even variable protocols of the same assays between different laboratories. These problems have lead the American Society of Reproductive Medicine Practice Committee report to state that “existing data relating to relationship between DNA fragmentation and reproductive outcomes too limited to routinely use” Their most favorable conclusion is that the effect of SDF on IUI, IVF, and ICSI may be clinically informative – hardly an overwhelming endorsement (2). While odds ratios are useful for describing associations in populations, they are not proper statistical metrics by which diagnostic tests are judged. When the results of individual patient’s SDF assays are used to direct those individual’s therapy, the assays are being used as diagnostic tests. The metrics by which diagnostic tests are evaluated are sensitivity, specificity, and the area under the Receiver Operating Characteristic (ROC) curves. The relationship between SDF and ART outcomes have been evaluated by at least 7 prior meta-analyses – all of which used odds ratios or relative risk ratios. Overall the results have been inconclusive. Li et al. reported that SDF was associated with IVF pregnancy rates but not with ICSI outcomes (3). Collins reported that sperm DNA damage predicts ART outcome, but the results of testing would not necessarily affect the decision to proceed with ART because the effects were likely clinically insignificant (4). Most recently, Simon determined that the association depends on the type of assay used. There was no association of SCSA and ART outcomes while there was a neDIffErENCE Of OPINION Vol. 44 (4): 676-679, July August, 2018

international braz j urol

Testicular versus ejaculated sperm should be used for intracytoplasmic sperm injection (ICSI) in cases of infertility associated with sperm DNA fragmentation | Opinion: No