Evaluation of sperm chromatin structure and DNA strand breaks is an important part of clinical male fertility assessment

As reviewed by Agarwal et al. (1) and recently stated by Vu Bach and Schlegel (2), “numerous studies have attempted to assess the association between elevated sperm DNA fragmentation (SDF) and ART outcomes. Unfortunately, variations between SDF assays, protocols, and thresholds and differences in study populations have resulted in systematic reviews and meta-analyses fraught with heterogeneity and unable to come to robust conclusions”. However, these early meta-analyses were considered a near impossible task leading to vague and questionable conclusions. Recent studies have refined protocols for the Sperm Chromatin Structure Assay (SCSA) (3,4) TUNEL (5), SCD (6) and COMET (7) tests. A major consideration for standardizing a protocol is to identify the SDF thresholds. While this has often been described as a single% SDF, e.g., 30% listed as the SCSA threshold in Agarwal et al. (1), more recent SCSA studies have listed two or three thresholds depending on the method of fertilization (see below).