Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

Abstract

Background Sperm DNA damage is common in infertile men and is associated with poor semen parameters but the impact of an isolated sperm abnormality on sperm DNA damage has not been studied. Objective To evaluate sperm DNA damage in a large cohort of infertile men with isolated sperm defects. Design, setting and participants Retrospective study of 1084 consecutive, non-azoospermic infertile men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). Outcome measurements and statistical analysis We examined and compared clinical parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF, assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay) in the three groups of men. Results and limitations The mean (±SD) %SDF was significantly higher in the iAstheno compared to the iOligo and iTerato groups (25.0±14.0 vs. 19.2±11.6 and 20.7±12.1 %, respectively, P<0.0001). Similarly, the proportion of men with high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo and iTerato groups (31 % vs. 18 % and 19 %, respectively, P<0.0001). In the group of 713 men with iAstheno, %SDF was positively correlated with paternal age (r=0.20, P<0.0001) and inversely correlated with %progressive motility (r=−0.18, P<0.0001). In the subset of 218 men with iTerato, %SDF was also positively correlated with paternal age (r=0.15, P=0.018) and inversely correlated with %progressive motility (r=−0.26, P=0.0001). Conclusions In this large cohort of infertile men with isolated sperm abnormalities, we have found that the sperm DNA fragmentation level is highest in the men with sperm motility defects and that 31 % of these men have high levels of sperm DNA fragmentation. The data indicate that poor motility is the sperm parameter abnormality most closely related to sperm DNA damage.

Sperm DNA fragmentation is related to sperm morphological staining patterns

“…Several investigators observed lower sDNAfrag in men with higher sperm concentration, total motility, progressive motility and normal morphology (Belloc et al, 2014;Moskovtsev et al, 2009;Oosterhuis et al, 2000;Shen et al, 2002;Zhang et al, 2008), whereas others showed that these parameters are not correlated with sDNAfrag (Ricci et al, 2002). However, after use of sperm-preparation techniques, results appear more consistent, several reports finding that after swim-up the percentage of sDNAfrag was negatively correlated with motility and morphology (Lopes et al, 1998;Sharbatoghli et al, 2012), with the same results observed after the use of DGC (Sakkas et al, 1999).…”

“…This damage can then affect oocyte activation after fertilization (Gannon et al, 2014). Various putative causes of sperm DNA fragmentation (sDNAfrag) have been discussed: apoptosis, abortive spermatogenesis, genetic factors, meiosis and spermiogenesis defects, and oxidative stress (Belloc et al, 2014;Benkhalifa et al, 2014). Whatever the origin, the detrimental effects of increased rates of sDNAfrag on male fertility have been clearly described (Sakkas and Alvarez, 2010).…”

Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years

“…These findings are consistent with many studies reporting a positive correlation between increasing male age and sperm DNA damage (Moskovtsev, Willis, & Mullen, ; Ramasamy et al, ; Sharma et al, ; Zitzmann, ) doubling from 25 to 55 years of age (Spanò et al, ). Indeed, APA could cause sperm DNA fragmentation (Agarwal, Makker, & Sharm, ; Belloc, Benkhalifa, Cohen‐Bacrie, Dalleac, Chahine, et al, ; Johnson et al, ; Nijs et al, ; Singh, Muller, & Berger, ; Wyrobek et al, ) and chromatin decondensation (Belloc et al, ; Nijs et al, ; Wyrobek et al, ). Moreover, there is relative linear correlation between APA and sperm aneuploidy rate (Agarwal et al, ; Sloter, Nath, Eskenazi, & Wyrobek, ; Sloter, Marchetti, et al, ; Wyrobek et al, ).…”

“…The last two decades many studies highlighted the importance of male fertility declining and spermatogenesis clock dysregulation (Skakkebaek et al, ). However, until today there is a lack of consensus concerning APA contribution on sperm parameters (Alshahrani et al, ; Andolz, Bielsa, & Vila, ; Fisch, Goluboff, & Olson, ; Kidd, Eskenazi, & Wyrobek, ), sperm DNA integrity (Belloc, Benkhalifa, Cohen‐Bacrie, Dalleac, Chahine, et al, ; Sartorelli, Mazzucatto, & de Pina‐Neto, ; Singh, Muller, & Berger, ; Sharma et al, ; Stone, Alex, Werlin, & Marrs, ), embryo development, clinical outcomes (Dain, Auslander, & Dirnfeld, ; Ferreira, Braga, Bonetti, Pasqualotto, & Iaconelli, ; Mathieu, Ecochard, & Bied, ) genetic and epigenetic state of fetus (Jyothy, Kumar, & Mallikarjuna, ), and/or of offspring (Sharma et al, ). It seems important to elucidate the risks to develop epigenetic diseases with paternal origin including autism and schizophrenia (Gingrich, ).…”

“…It seems important to elucidate the risks to develop epigenetic diseases with paternal origin including autism and schizophrenia (Gingrich, ). For this reason completing conventional sperm analysis with minimal SGD tests including sperm DNA fragmentation, chromatin decondensation, and aneuploidy can be informative to assess risks (Belloc, Benkhalifa, Cohen‐Bacrie, Dalleac, A., Amar, et al, ; Belloc, Benkhalifa, Cohen‐Bacrie, Dalleac, Chahine, et al, ).…”