title: Clinical significance of sperm DNA damage in assisted reproduction outcome.
abstract: 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.
authors.affiliation: Centre for Public Health, Reproductive Medicine, Institute of Clinical Science, Queens University of Belfast, Grosvenor Road, Belfast BT12 6BJ, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Simon
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brunborg
authors.forename: Michael
authors.initials: M
authors.lastname: Stevenson
authors.forename: Deborah
authors.initials: D
authors.lastname: Lutton
authors.forename: Joanne
authors.initials: J
authors.lastname: McManus
authors.forename: Sheena E M
authors.initials: SE
authors.lastname: Lewis
mesh_terms: 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