Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation

Background: It is known that repeated failure of assisted reproduction treatment (ART) can be due to a paternal effect. This study was undertaken to analyse the possible relationship between ART failure and sperm DNA fragmentation. Methods: Zygote morphology and the percentage of spermatozoa with fragmented DNA (assessed by TUNEL) were compared in two groups using donor oocytes for ICSI attempts. The experimental group consisted of 18 infertile couples who had each undergone three previous failed ART attempts. The control group included 18 randomly selected infertile couples undergoing their first ICSI attempt. Both groups used sibling oocytes from the same donors. Results: In 10 couples of the experimental group, the adverse paternal effect was evident as early as the zygote stage. This early paternal effect was not associated with sperm DNA fragmentation. In eight couples of the experimental group, the adverse paternal effect did not produce any perceptible deterioration of zygote morphology. However, this late paternal effect was associated with an increased percentage of spermatozoa with fragmented DNA. Conclusions: Early paternal effect can compromise ART outcomes in the absence of increased sperm DNA fragmentation. Evaluation of sperm DNA integrity is useful to detect late paternal effect, which is not associated with morphological abnormalities at the zygote and early cleavage stages.