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Paternal factors, specifically low sperm motility and high levels of moderate DNA damage, predict increased rates of aneuploidy in embryos from egg donor cycles.

Research presented at the Pacific Coast Fertility Society, 2007.

Background and Significance: Aneuploidies, numerical chromosome errors, are common in human embryos and are associated with increasing maternal age. Although sperm aneuploidy rates have been shown to be elevated in infertile men with extremely poor semen quality, the effect of paternal influences (age, semen quality and sperm DNA fragmentation) on frequency of aneuploidy in embryos is less well known.
Objectives: The aim of this study was to evaluate the relationship between sperm quality, as defined by conventional semen parameters and measurements of sperm DNA integrity, and incidence of chromosomally abnormal embryos. To eliminate any effect of maternal age, only embryos obtained from egg donation cycles were examined.
Materials and Methods: A retrospective study of 23 egg donation cycles (mean age of donors: 24 ± 3.1) with preimplantation genetic diagnosis (PGD) performed in a private infertility clinic. Semen analyses and sperm DNA evaluation using the Sperm Chromatin Structure Assay (SCSA) were performed on the semen specimen prior to processing for insemination. Multi-color fluorescent in situ hybridization (FISH) for chromosomes 13,18, 21, X and Y (Vysis) was applied on single cells biopsied from day 3 embryos that had cleaved to ≥5 cells (n = 200). Embryos were considered aneuploid if the PGD result indicated monosomy, trisomy, complex abnormal, haploidy or polyploidy. Statistical analysis was performed using Spearman’s rank correlation coefficient.
Results: Male age (mean: 41 ± 5.7 y) did not correlate with aneuploidy rate (mean: 37%, range 0-80%). There was no relationship between the total DNA Fragmentation Index (DFI, percent of sperm cells containing damaged DNA) and aneuploidy rate. Interestingly, however, there was a significant correlation between the percentage of sperm with moderate DNA fragmentation (moderate % DFI) and rate of aneuploidy (p< 0.05). There was no association between HDS (percent of sperm with immature chromatin), sperm concentration or percentage normal morphology and aneuploidy rate. Percentage sperm motility was significantly negatively correlated with embryo aneuploidy rate (p<0.05).
Conclusions: This preliminary study suggests that two indicators of poor sperm quality, reduced sperm motility and increased levels of moderate DNA fragmentation, are related to higher aneuploidy rates in preimplantation embryos. In both situations, ICSI may not select out the sperm of highest quality for oocyte injection. This data lends support to previous studies suggesting a paternal influence on embryo development, possibly mediated by centrosomal defects, mitochondrial dysfunction or abnormal oocyte activation.


 

 

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