Association between sperm DNA fragmentation and aneuploidy rate in assisted reproduction patients

Abstract

OBJECTIVE: Damage to sperm chromatin, such as DNA fragmentation that has been associated with male infertility, unsuccessful conception and poor sustained pregnancy. However few studies have shown that fragmented DNA can be associated with chromosomal aberrations in sperm. Therefore the aim of this study was to analyze the frequency of sex-chromosomal aneuploidy in spermatozoa of non-fragmented (NF) and fragmented (F) assisted reproduction treatment (ART) patients, and to correlate aneuploidy rate between each group. DESIGN: Prospective laboratory study. MATERIALS AND METHODS: Sperm DNA fragmentation rate (SDFR) was assessed by sperm chromatin dispersion (SCD) test and patients were divided in NF (SDFR ≤16%) and F (SDFR>16%). Aneuploidy rate evaluated by Fluorescence in situ hybridization (FISH) with direct label probes specific for chromosome 18, X and Y (Kreatech Diagnosis, Netherlands). A total of 500 spermatozoa were analyzed per sample. Statistical analysis was performed with Mann-Whitney test (median; range), Spearman's correlation test and binary logistic regression. Every calculation was done by Graph Pad Prism 4 program. RESULTS: Twenty samples from ART patients were assigned to F (n=10) and NF (n=10). The rate of gonosomal aneuploidy was lower in NF (11.5; 5-43) than in F (28; 14-56; P<0.05). Likelihood for aneuploidy in spermatozoa DNA is 2-fold increased in men with fragmented sperm DNA (odds ratio: 2.01; 95% confidence interval=1.6-2.4; p<0.001). Aneuploidy rate and fragmentation of sperm DNA were significantly correlated (r=0.56; P<0.01). CONCLUSIONS: Sperm DNA fragmentation is strongly correlated to aneuploidy rate and may be a consequence of aneuploidy during sperm maturation. Additionally our findings suggest that males with fragmented sperm DNA have risk of fathering aneuploid offspring.