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High, But Not Moderate, Levels Of Sperm DNA Fragmentation Are Predictive Of Poor Outcome In Egg Donation Cycles.

This research presented at the American Society for Reproductive Medicine (ASRM), Philadelphia, 2004..

CA Adams, LS Anderson and SH Wood. Reproductive Sciences Center, La Jolla, CA, USA.

Objective: The DNA Fragmentation Index (DFI), as measured by the Sperm Chromatin Structure Assay (SCSA), has been shown in several studies to be an independent predictor of male fertility potential in ART cycles. The DFI describes the percentage of sperm with DNA fragmentation, that fragmentation being the result, hypothetically, of faulty DNA repair mechanisms. It has been proposed that high quality oocytes may have the ability to repair sperm whose DNA has experienced oxidative damage. The purpose of the present study was to explore whether donor eggs are capable of compensating for suboptimal sperm chromatin integrity. .

Design: A retrospective analysis of 50 consecutive egg donor cycles (mean age of donors: 23.6y ± 3.4) in a private IVF clinic.

Materials and Methods: The SCSA was performed on all males undergoing egg donation cycles. Cycles were assigned into one of three groups based on the DFI, as described in previously published studies: Group A (Low DNA fragmentation): <15% (mean: 10.1%, n= 22), Group B (Moderate DNA fragmentation): 15-30% (mean: 22.4, n=19), Group C (High DNA fragmentation): >30% (mean: 47.7%, n = 9). Fertilization rates (2PN), embryo quality, implantation, and pregnancy rates were assessed. For determination of on-going pregnancy and implantation rates, the number of gestational sacs with fetal cardiac activity was evaluated. Data was evaluated for statistical significance utilizing the ANOVA or chi-square as appropriate.

Results: There was no significant difference in the mean number of embryos transferred in each group. Pregnancy and implantation rates were not significantly different between Groups A and B (73% vs. 74% and 31% vs. 30%). However, Group C had a significantly lower pregnancy rate (22%, p<0.025) and implantation rate (13%, p<0.025). Fertilization rates were not significantly different among Groups A, B and C (mean 2PN: 77%, 74% and 64%, respectively). Likewise, the percentage of good quality day 2 or 3 embryos (<25% fragmentation) was also not significantly different among the three groups (86%, 86% and 93%, respectively)..

Conclusions: The data indicates that men with high levels of DNA fragmentation (DFI >30%) have significantly lower pregnancy and implantation rates in egg donation cycles, despite no significant difference in fertilization rate or cleavage-stage embryo quality. Thus, the 30% DFI threshold appears to be an important prognostic indicator even in egg donation cycles. However, since there is no apparent deleterious effect on pregnancy or implantation rates of moderate levels of DNA fragmentation (15-30%) when an egg donor is used, it may be that good quality oocytes from young women are able to repair moderate, but not high, levels of sperm DNA damage.