Clinical significance of sperm DNA damage in assisted reproduction outcome.
BACKGROUND
Sperm DNA damage shows great promise as a biomarker of infertility. The study aim is to determine the usefulness of DNA fragmentation (DF), including modified bases (MB), to predict assisted reproduction treatment (ART) outcomes.


METHODS
DF in 360 couples (230 IVF and 130 ICSI) was measured by the alkaline Comet assay in semen and in sperm following density gradient centrifugation (DGC) and compared with fertilization rate (FR), embryo cumulative scores (ECS(1)) for the total number of embryos/treatment, embryos transferred (ECS(2)), clinical pregnancy (CP) and spontaneous pregnancy loss. MB were also measured using formamidopyrimidine DNA glycosylase to convert them into strand breaks.


RESULTS
In IVF, FR and ECS decreased as DF increased in both semen and DGC sperm, and couples who failed to achieve a CP had higher DF than successful couples (+12.2% semen, P = 0.004; +9.9% DGC sperm, P = 0.010). When MB were added to existing strand breaks, total DF was markedly higher (+17.1% semen, P = 0.009 and +13.8% DGC sperm, P = 0.045). DF was not associated with FR, ECS or CP in either semen or DGC sperm following ISCI. In contrast, by including MB, there was significantly more DNA damage (+16.8% semen, P = 0.008 and +15.5% DGC sperm, P = 0.024) in the group who did not achieve CP.


CONCLUSIONS
DF can predict ART outcome for IVF. Converting MB into further DNA strand breaks increased the test sensitivity, giving negative correlations between DF and CP for ICSI as well as IVF.
Simon
Luke
L
Centre for Public Health, Reproductive Medicine, Institute of Clinical Science, Queens University of Belfast, Grosvenor Road, Belfast BT12 6BJ, UK.
Brunborg
Gunnar
G
Stevenson
Michael
M
Lutton
Deborah
D
McManus
Joanne
J
Lewis
Sheena E M
SE
D000022:Abortion, Spontaneous; D020552:Comet Assay; D053938:DNA Fragmentation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007246:Infertility / Q000628:therapy*; D008297:Male; D011237:Predictive Value of Tests; D011247:Pregnancy; D018873:Pregnancy Rate; D055101:Semen Analysis; D013094:Spermatozoa / Q000502:physiology*; D016896:Treatment Outcome