Advanced Paternal Age and Sperm DNA Fragmentation: A Systematic Review

Abstract

Purpose Male ageing is often associated with defective sperm DNA remodeling mechanisms that result in poorly packaged chromatin and a decreased ability to repair DNA strand breaks. However, the impact of advanced paternal age on DNA fragmentation remains inconclusive. The aim of the present systematic review was to investigate the impact of advancing paternal age (APA) on DNA fragmentation. Materials and Methods We conducted a thorough search of listed publications in Scopus, PubMed, and EMBASE, in accordance with the PRISMA guidelines. Results We identified 3,120 articles, of which nineteen were selected for qualitative analysis, resulting in a sample of 40,668 men. Of the 19 articles evaluating the impact of APA on DFI% (DNA fragmentation Index) included, 4 were on Normozoospermic and subfertile men, 3 on normozoospermic, Oligoasthenoteratozoospermic and Teratozoospermic, 6 on fertile and infertile men, 4 on just infertile men, and 2 evaluated a general population. Seventeen of the ninrnteen studies demonstrated APA's effect and impact on DFI%. Conclusions Although there was no universal definition for APA, the present review suggests that older age is associated with increased DFI. In elderly men with normal semen parameters, further studies should be performed to assess the clinical implications of DFI, as a conventional semen analysis can often fail to detect an etiology for infertility.

Influence of sperm DNA fragmentation on the clinical outcome of in vitro fertilization-embryo transfer (IVF-ET)

“…In the current study, the analysis of 1638 IVF/ICSI cycles showed that the sperm DFI was significantly positively correlated with male age, indicating that the degree of sperm DNA fragmentation increased with age ( Supplementary Table 1 ). This is consistent with the findings of Bellver ( 15 ), Ghanbarzadeh ( 16 ), Zhang ( 17 ), Gonzalez ( 18 ), Lu ( 19 ) and Belloc ( 20 ). The sperm DFI was significantly and positively correlated with abstinence days, semen volume, immotile sperm percentage, sperm high-staining HDS percentage and other parameters, suggesting that the increase in abstinence days may increase semen volume, but the immotile sperm percentage and sperm high-staining HDS percentage may increase at the same time.…”

Whether the Effect of Sperm DNA Fragmentation on the Clinical and Laboratory Outcomes Changes with the Paternal age in the intracytoplasmic sperm injection Cycles of Donor Oocytes

“…This is the first study to classify the patients according to paternal age and the SDF rate and to correlate with the clinical and laboratory outcomes in the ICSI cycles of donor oocytes. In most of the studies, paternal age correlation was limited to semen parameters like volume, count, motility, morphology, and SDF rates (14,17,30). Female factors like age, ovarian reserve, and oocyte quality play a major role in determining the clinical and laboratory outcomes (10,28,31).…”

“…The negative influence of SDF on the laboratory outcomes and clinical outcomes in in-vitro fertilization (IVF) cycles and/or intracytoplasmic sperm injection (ICSI) was reported by various studies and meta-analyses (7)(8)(9)(10)(11)(12)(13). Paternal age has been linked to SDF in various studies; an increase in paternal age has a positive correlation with SDF (14,15). Few studies have reported paternal age of 40 years and above has increased the risk for SDF (16,17).…”

Advanced Paternal Age and Future Generations

“…One proposed mechanism of the adverse reproductive outcomes in natural and assisted reproduction is impaired sperm chromatin integrity and increased DNA fragmentation rates ( 52 ). In a recent systematic review, 17 out of 19 studies demonstrated an association of advanced paternal age with significant increase in DNA fragmentation ( 53 ), mostly measured by Sperm Chromatin Structure Assay ® and sperm chromatin dispersion test. The two studies that did not find the effect of advanced paternal age on sperm DNA fragmentation utilized terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay.…”