Sperm DNA Fragmentation: Consequences for Reproduction

  • Luke Simon
  • Benjamin Emery
  • Douglas T. CarrellEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1166)


DNA fragmentation, or the accumulation of single- and double-strand DNA breaks, is a common property of sperm, and an increase in the level of sperm DNA fragmentation is known to influence natural reproduction. The effect of sperm DNA fragmentation on male infertility and assisted reproductive treatment (ART) outcomes remains controversial and is one of the most frequently debated topics of reproductive medicine. For the past 30 years, a number of assays have been developed to quantify the level of sperm DNA fragmentation. In this chapter, we review the causes of sperm DNA fragmentation, describe the commonly used tests to evaluate these abnormalities, and perform a systematic review of existing studies to determine the impact of sperm DNA fragmentation on male fertility and ART outcomes.


Sperm DNA fragmentation Comet assay SCSA TUNEL assay SCD assay Male infertility ART outcomes 


  1. Abd-Elmoaty MA et al (2010) Increased levels of oxidants and reduced antioxidants in semen of infertile men with varicocele. Fertil Steril 94(4):1531–1534PubMedPubMedCentralCrossRefGoogle Scholar
  2. Agarwal A, Allamaneni SS (2005) Sperm DNA damage assessment: a test whose time has come. Fertil Steril 84(4):850–853PubMedCrossRefGoogle Scholar
  3. Agarwal A et al (2014) Reactive oxygen species and sperm DNA damage in infertile men presenting with low level leukocytospermia. Reprod Biol Endocrinol 12:1–8CrossRefGoogle Scholar
  4. Ahmadi A, Ng SC (1999) Fertilizing ability of DNA-damaged spermatozoa. J Exp Zool 284(6):696–704PubMedCrossRefGoogle Scholar
  5. Aitken RJ (2012) Aetiology of defective sperm function and DNA damage in the male germ line. J Reprod Immunol 94(1):7–8CrossRefGoogle Scholar
  6. Aitken RJ, De Iuliis GN (2007) Origins and consequences of DNA damage in male germ cells. Reprod Biomed Online 14(6):727–733PubMedCrossRefGoogle Scholar
  7. Aitken RJ, De Iuliis GN (2010) On the possible origins of DNA damage in human spermatozoa. Mol Hum Reprod 16(1):3–13PubMedCrossRefGoogle Scholar
  8. Aitken RJ, Koppers AJ (2011) Apoptosis and DNA damage in human spermatozoa. Asian J Androl 13(1):36–42PubMedCrossRefGoogle Scholar
  9. Aitken RJ et al (2005) Impact of radio frequency electromagnetic radiation on DNA integrity in the male germline. Int J Androl 28(3):171–179PubMedCrossRefGoogle Scholar
  10. Alkan I et al (1997) Reactive oxygen species production by the spermatozoa of patients with idiopathic infertility: relationship to seminal plasma antioxidants. J Urol 157(1):140–143PubMedCrossRefGoogle Scholar
  11. Alkhayal A et al (2013) Sperm DNA and chromatin integrity in semen samples used for intrauterine insemination. J Assist Reprod Genet 30(11):1519–1524PubMedPubMedCentralCrossRefGoogle Scholar
  12. Andersen AG et al (2002) Time to pregnancy in relation to semen quality assessed by CASA before and after sperm separation. Hum Reprod 17(1):173–177PubMedCrossRefGoogle Scholar
  13. Anderson D et al (2003) Oestrogenic compounds and oxidative stress (in human sperm and lymphocytes in the Comet assay). Mutat Res 544(2–3):173–178PubMedCrossRefGoogle Scholar
  14. Anifandis G et al (2015) Sperm DNA fragmentation measured by Halosperm does not impact on embryo quality and ongoing pregnancy rates in IVF/ICSI treatments. Andrologia 47(3):295–302PubMedCrossRefGoogle Scholar
  15. Aoki VW et al (2005) DNA integrity is compromised in protamine-deficient human sperm. J Androl 26(6):741–748PubMedCrossRefGoogle Scholar
  16. Aoki VW et al (2006) Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability. Fertil Steril 86(5):1408–1415CrossRefGoogle Scholar
  17. Aravindan GR et al (1997) Susceptibility of human sperm to in situ DNA denaturation is strongly correlated with DNA strand breaks identified by single-cell electrophoresis. Exp Cell Res 236(1):231–237PubMedCrossRefGoogle Scholar
  18. Avendano C et al (2010) DNA fragmentation of normal spermatozoa negatively impacts embryo quality and intracytoplasmic sperm injection outcome. Fertil Steril 94(2):549–557PubMedCrossRefGoogle Scholar
  19. Baker K et al (2013) Pregnancy after varicocelectomy: impact of postoperative motility and DFI. Urology 81(4):760–766PubMedCrossRefGoogle Scholar
  20. Bakos HW et al (2007) Elevated glucose levels induce lipid peroxidation and DNA damage in human spermatozoa. Aust N Z J Obstet Gynaecol 47:A1–A1CrossRefGoogle Scholar
  21. Barbieri ER et al (1999) Varicocele-associated decrease in antioxidant defenses. J Androl 20(6):713–717PubMedGoogle Scholar
  22. Barroso G, Morshedi M, Oehninger S (2000) Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod 15(6):1338–1344PubMedCrossRefGoogle Scholar
  23. Benchaib M et al (2003) Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod 18(5):1023–1028PubMedCrossRefGoogle Scholar
  24. Benchaib M et al (2007) Sperm deoxyribonucleic acid fragmentation as a prognostic indicator of assisted reproductive technology outcome. Fertil Steril 87(1):93–100PubMedCrossRefGoogle Scholar
  25. Bianchi PG et al (1993) Effect of deoxyribonucleic acid protamination on fluorochrome staining and in situ nick-translation of murine and human mature spermatozoa. Biol Reprod 49(5):1083–1088PubMedCrossRefGoogle Scholar
  26. Boe-Hansen GB, Ersboll AK, Christensen P (2005a) Variability and laboratory factors affecting the sperm chromatin structure assay in human semen. J Androl 26(3):360–368PubMedCrossRefGoogle Scholar
  27. Boe-Hansen GB, Ersbøll AK, Christensen P (2005b) Variability and laboratory factors affecting the sperm chromatin structure assay in human semen. J Androl 26(3):360–368PubMedCrossRefGoogle Scholar
  28. Boe-Hansen GB et al (2006) The sperm chromatin structure assay as a diagnostic tool in the human fertility clinic. Hum Reprod 21(6):1576–1582PubMedCrossRefGoogle Scholar
  29. Bonde JPE et al (1998) Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet 352(9135):1172–1177PubMedCrossRefGoogle Scholar
  30. Borini A et al (2006) Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod 21(11):2876–2881PubMedCrossRefPubMedCentralGoogle Scholar
  31. Buck Louis GM et al (2014) Semen quality and time to pregnancy: the Longitudinal Investigation of Fertility and the Environment Study. Fertil Steril 101(2):453–462PubMedCrossRefGoogle Scholar
  32. Bungum M et al (2004) The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. Hum Reprod 19(6):1401–1408PubMedCrossRefGoogle Scholar
  33. Bungum M et al (2007) Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod 22(1):174–179PubMedCrossRefGoogle Scholar
  34. Bungum M et al (2008) Sperm chromatin structure assay parameters measured after density gradient centrifugation are not predictive for the outcome of ART. Hum Reprod 23(1):4–10PubMedCrossRefGoogle Scholar
  35. Caglar GS et al (2007) Semen DNA fragmentation index, evaluated with both TUNEL and Comet assay, and the ICSI outcome. In Vivo 21(6):1075–1080PubMedGoogle Scholar
  36. Castillo J et al (2011) Protamine/DNA ratios and DNA damage in native and density gradient centrifuged sperm from infertile patients. J Androl 32(3):324–332PubMedCrossRefGoogle Scholar
  37. Check JH et al (2005) Effect of an abnormal sperm chromatin structural assay (SCSA) on pregnancy outcome following (IVF) with ICSI in previous IVF failures. Arch Androl 51(2):121–124PubMedCrossRefGoogle Scholar
  38. Collins JA, Barnhart KT, Schlegel PN (2008) Do sperm DNA integrity tests predict pregnancy with in vitro fertilization? Fertil Steril 89(4):823–831PubMedCrossRefGoogle Scholar
  39. Cooper TG et al (2010) World Health Organization reference values for human semen characteristics. Hum Reprod Update 16(3):231–245CrossRefGoogle Scholar
  40. Dar S et al (2013) In vitro fertilization-intracytoplasmic sperm injection outcome in patients with a markedly high DNA fragmentation index (>50%). Fertil Steril 100(1):75–80PubMedCrossRefGoogle Scholar
  41. Daris B et al (2010) Sperm morphological abnormalities as indicators of DNA fragmentation and fertilization in ICSI. Arch Gynecol Obstet 281(2):363–367PubMedCrossRefGoogle Scholar
  42. Donnelly ET, McClure N, Lewis SE (2001) Cryopreservation of human semen and prepared sperm: effects on motility parameters and DNA integrity. Fertil Steril 76(5):892–900PubMedPubMedCentralCrossRefGoogle Scholar
  43. Duran EH et al (2002) Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod 17(12):3122–3128PubMedCrossRefGoogle Scholar
  44. Erenpreiss J et al (2002) Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal semen samples. J Androl 23(5):717–723PubMedGoogle Scholar
  45. Erenpreiss J et al (2006) Sperm chromatin structure and male fertility: biological and clinical aspects. Asian J Androl 8(1):11–29PubMedCrossRefGoogle Scholar
  46. Esbert M et al (2011) Impact of sperm DNA fragmentation on the outcome of IVF with own or donated oocytes. Reprod Biomed Online 23(6):704–710PubMedCrossRefGoogle Scholar
  47. Evenson D, Jost L (2000) Sperm chromatin structure assay is useful for fertility assessment. Methods Cell Sci 22(2–3):169–189PubMedCrossRefGoogle Scholar
  48. Evenson DP, Wixon R (2005) Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm Chromatin Structure Assay (SCSA). Toxicol Appl Pharmacol 207(2. Suppl):532–537PubMedCrossRefGoogle Scholar
  49. Evenson DP, Darzynkiewicz Z, Melamed MR (1980) Relation of mammalian sperm chromatin heterogeneity to fertility. Science 210(4474):1131–1133PubMedCrossRefGoogle Scholar
  50. Evenson DP et al (1999) Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod 14(4):1039–1049PubMedCrossRefGoogle Scholar
  51. Evenson DP, Larson KL, Jost LK (2002) Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Androl 23(1):25–43PubMedCrossRefGoogle Scholar
  52. Fang L, et al. (2011) [A study on correlation between sperm DNA fragmentation index and age of male, various parameters of sperm and in vitro fertilization outcome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 28(4):432–435Google Scholar
  53. Fatehi AN et al (2006) DNA damage in bovine sperm does not block fertilization and early embryonic development but induces apoptosis after the first cleavages. J Androl 27(2):176–188PubMedCrossRefGoogle Scholar
  54. Feijó CM, Esteves SC (2014) Diagnostic accuracy of sperm chromatin dispersion test to evaluate sperm deoxyribonucleic acid damage in men with unexplained infertility. Fertil Steril 101(1):58–63.e3PubMedCrossRefGoogle Scholar
  55. Fernández JL, Gosálvez J (2002) Application of FISH to detect DNA damage. DNA breakage detection-FISH (DBD-FISH). Methods Mol Biol 203:203–216PubMedGoogle Scholar
  56. Fernandez JL et al (2003) The sperm chromatin dispersion test: a simple method for the determination of sperm DNA fragmentation. J Androl 24(1):59–66PubMedGoogle Scholar
  57. Ford HB, Schust DJ (2009) Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2(2):76–83PubMedPubMedCentralGoogle Scholar
  58. Fraser L (2004) Structural damage to nuclear DNA in mammalian spermatozoa: its evaluation techniques and relationship with male infertility. Pol J Vet Sci 7(4):311–321PubMedGoogle Scholar
  59. Frydman N et al (2008) Adequate ovarian follicular status does not prevent the decrease in pregnancy rates associated with high sperm DNA fragmentation. Fertil Steril 89(1):92–97PubMedCrossRefGoogle Scholar
  60. Gandini L et al (2004) Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage. Hum Reprod 19(6):1409–1417PubMedCrossRefGoogle Scholar
  61. Giwercman A et al (2010) Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study. Int J Androl 33(1):e221–e227PubMedPubMedCentralCrossRefGoogle Scholar
  62. Gorczyca W, Gong J, Darzynkiewicz Z (1993) Detection of DNA strand breaks in individual apoptotic cells by the in situ terminal deoxynucleotidyl transferase and nick translation assays. Cancer Res 53(8):1945–1951PubMedGoogle Scholar
  63. Gosalvez J et al (2013) Can DNA fragmentation of neat or swim-up spermatozoa be used to predict pregnancy following ICSI of fertile oocyte donors? Asian J Androl 15(6):812–818PubMedPubMedCentralCrossRefGoogle Scholar
  64. Gu LJ et al (2009) Sperm chromatin anomalies have an adverse effect on the outcome of conventional in vitro fertilization: a study with strictly controlled external factors. Fertil Steril 92(4):1344–1346PubMedCrossRefGoogle Scholar
  65. Gu LJ, et al. (2011) [Effects of abnormal structure of sperm chromatin on the outcome of in vitro fertilization and embryo transfer]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 28(2):156–159Google Scholar
  66. Guerin P, et al. (2005) [Impact of sperm DNA fragmentation on ART outcome]. Gynecol Obstet Fertil 33(9):665–668Google Scholar
  67. Hales BF, Barton TS, Robaire B (2005) Impact of paternal exposure to chemotherapy on offspring in the rat. J Natl Cancer Inst Monogr (34):28–31Google Scholar
  68. Hammadeh ME et al (2006) Comparison of reactive oxygen species concentration in seminal plasma and semen parameters in partners of pregnant and non-pregnant patients after IVF/ICSI. Reprod Biomed Online 13(5):696–706PubMedCrossRefGoogle Scholar
  69. Hammadeh ME et al (2008) Reactive oxygen species, total antioxidant concentration of seminal plasma and their effect on sperm parameters and outcome of IVF/ICSI patients. Arch Gynecol Obstet 277(6):515–526PubMedCrossRefGoogle Scholar
  70. Henkel R et al (2003) DNA fragmentation of spermatozoa and assisted reproduction technology. Reprod Biomed Online 7(4):477–484PubMedCrossRefGoogle Scholar
  71. Host E et al (1999) DNA strand breaks in human sperm cells: a comparison between men with normal and oligozoospermic sperm samples. Acta Obstet Gynecol Scand 78(4):336–339PubMedCrossRefGoogle Scholar
  72. Høst E et al (1999) DNA strand breaks in human sperm cells: a comparison between men with normal and oligozoospermic sperm samples. Acta Obstet Gynecol Scand 78(4):336–339PubMedCrossRefGoogle Scholar
  73. Hsu PC et al (2006) Sperm DNA damage correlates with polycyclic aromatic hydrocarbons biomarker in coke-oven workers. Int Arch Occup Environ Health 79(5):349–356PubMedCrossRefGoogle Scholar
  74. Huang CC et al (2005) Sperm DNA fragmentation negatively correlates with velocity and fertilization rates but might not affect pregnancy rates. Fertil Steril 84(1):130–140PubMedCrossRefGoogle Scholar
  75. Hughes CM et al (1996) A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay. Mol Hum Reprod 2(8):613–619PubMedCrossRefGoogle Scholar
  76. Hughes CM, McKelvey-Martin VJ, Lewis SEM (1999) Human sperm DNA integrity assessed by the Comet and ELISA assays. Mutagenesis 14(1):71–75PubMedCrossRefGoogle Scholar
  77. Irvine DS et al (2000) DNA integrity in human spermatozoa: relationships with semen quality. J Androl 21(1):33–44PubMedGoogle Scholar
  78. Jiang HH, et al. (2011) [Sperm chromatin integrity test for predicting the outcomes of IVF and ICSI]. Zhonghua Nan Ke Xue 17(12):1083–1086Google Scholar
  79. Kennedy C et al (2011) Sperm chromatin structure correlates with spontaneous abortion and multiple pregnancy rates in assisted reproduction. Reprod Biomed Online 22(3):272–276PubMedCrossRefGoogle Scholar
  80. Klaude M et al (1996) The comet assay: mechanisms and technical considerations. Mutat Res 363(2):89–96PubMedCrossRefGoogle Scholar
  81. Koca Y et al (2009) Antioxidant activity of seminal plasma in fertile and infertile men. Arch Androl 49(5):355–359CrossRefGoogle Scholar
  82. Lackner JE et al (2008) Effect of leukocytospermia on fertilization and pregnancy rates of artificial reproductive technologies. Fertil Steril 90(3):869–871PubMedCrossRefGoogle Scholar
  83. Larson KL et al (2000) Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. Hum Reprod 15(8):1717–1722PubMedCrossRefGoogle Scholar
  84. Larson-Cook KL et al (2003) Relationship between the outcomes of assisted reproductive techniques and sperm DNA fragmentation as measured by the sperm chromatin structure assay. Fertil Steril 80(4):895–902PubMedCrossRefGoogle Scholar
  85. Lazaros L et al (2013) Sperm flow cytometric parameters are associated with ICSI outcome. Reprod Biomed Online 26(6):611–618PubMedCrossRefGoogle Scholar
  86. Lewis SE, Agbaje IM (2008) Using the alkaline comet assay in prognostic tests for male infertility and assisted reproductive technology outcomes. Mutagenesis 23(3):163–170PubMedCrossRefGoogle Scholar
  87. Lewis SE et al (2004) An algorithm to predict pregnancy in assisted reproduction. Hum Reprod 19(6):1385–1394PubMedCrossRefGoogle Scholar
  88. Li N, Jiang L (2011) Effect of sperm DNA on the outcome of in vitro fertilization-embryo transfer. Guangxi Med J 33(3):257–260Google Scholar
  89. Li Z et al (2006) Correlation of sperm DNA damage with IVF and ICSI outcomes: a systematic review and meta-analysis. J Assist Reprod Genet 23(9–10):367–376PubMedPubMedCentralCrossRefGoogle Scholar
  90. Lin MH et al (2008) Sperm chromatin structure assay parameters are not related to fertilization rates, embryo quality, and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection, but might be related to spontaneous abortion rates. Fertil Steril 90(2):352–359PubMedCrossRefGoogle Scholar
  91. Lopes S et al (1998) Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen samples and correlates with failed fertilization in intracytoplasmic sperm injection. Fertil Steril 69(3):528–532CrossRefGoogle Scholar
  92. Lopez G et al (2013) Diagnostic value of sperm DNA fragmentation and sperm high-magnification for predicting outcome of assisted reproduction treatment. Asian J Androl 15(6):790–794PubMedPubMedCentralCrossRefGoogle Scholar
  93. Manicardi GC et al (1995) Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility. Biol Reprod 52(4):864–867PubMedCrossRefGoogle Scholar
  94. Marchetti C et al (2002) Study of mitochondrial membrane potential, reactive oxygen species, DNA fragmentation and cell viability by flow cytometry in human sperm. Hum Reprod 17(5):1257–1265PubMedCrossRefGoogle Scholar
  95. McKelvey-Martin VJ et al (1997) Two potential clinical applications of the alkaline single-cell gel electrophoresis assay: (1). Human bladder washings and transitional cell carcinoma of the bladder; and (2). Human sperm and male infertility. Mutat Res 375(2):93–104PubMedCrossRefGoogle Scholar
  96. Meseguer M et al (2011) Effect of sperm DNA fragmentation on pregnancy outcome depends on oocyte quality. Fertil Steril 95(1):124–128PubMedCrossRefGoogle Scholar
  97. Micinski P et al (2009) The sperm chromatin structure assay (SCSA) as prognostic factor in IVF/ICSI program. Reprod Biol 9(1):65–70PubMedCrossRefGoogle Scholar
  98. Migliore L et al (2002) Assessment of sperm DNA integrity in workers exposed to styrene. Hum Reprod 17(11):2912–2918PubMedCrossRefGoogle Scholar
  99. Morris ID (2002) Sperm DNA damage and cancer treatment. Int J Androl 25(5):255–261PubMedCrossRefGoogle Scholar
  100. Morris ID et al (2002) The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development. Hum Reprod 17(4):990–998PubMedCrossRefGoogle Scholar
  101. Muriel L et al (2006) Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study. Hum Reprod 21(3):738–744PubMedCrossRefGoogle Scholar
  102. Nasr-Esfahani MH et al (2005) Effect of sperm DNA damage and sperm protamine deficiency on fertilization and embryo development post-ICSI. Reprod Biomed Online 11(2):198–205PubMedCrossRefGoogle Scholar
  103. Ni W et al (2014) Effect of sperm DNA fragmentation on clinical outcome of frozen-thawed embryo transfer and on blastocyst formation. PLoS One 9(4):e94956PubMedPubMedCentralCrossRefGoogle Scholar
  104. Nicopoullos JD et al (2008) Sperm DNA fragmentation in subfertile men: the effect on the outcome of intracytoplasmic sperm injection and correlation with sperm variables. BJU Int 101(12):1553–1560PubMedCrossRefGoogle Scholar
  105. Nijs M et al (2009) Chromomycin A3 staining, sperm chromatin structure assay and hyaluronic acid binding assay as predictors for assisted reproductive outcome. Reprod Biomed Online 19(5):671–684PubMedCrossRefGoogle Scholar
  106. Nijs M et al (2011) Correlation between male age, WHO sperm parameters, DNA fragmentation, chromatin packaging and outcome in assisted reproduction technology. Andrologia 43(3):174–179PubMedPubMedCentralCrossRefGoogle Scholar
  107. Nunez-Calonge R et al (2012) An improved experimental model for understanding the impact of sperm DNA fragmentation on human pregnancy following ICSI. Reprod Sci 19(11):1163–1168PubMedCrossRefGoogle Scholar
  108. Oh E et al (2005) Evaluation of immuno- and reproductive toxicities and association between immunotoxicological and genotoxicological parameters in waste incineration workers. Toxicology 210(1):65–80PubMedCrossRefGoogle Scholar
  109. Ola B et al (2001) Should ICSI be the treatment of choice for all cases of in-vitro conception? Considerations of fertilization and embryo development, cost effectiveness and safety. Hum Reprod 16(12):2485–2490PubMedCrossRefGoogle Scholar
  110. Oleszczuk K et al (2013) Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples. Andrology 1(3):357–360PubMedCrossRefGoogle Scholar
  111. Oliva R (2006) Protamines and male infertility. Hum Reprod Update 12(4):417–435PubMedCrossRefGoogle Scholar
  112. Olive PL et al (2001) Analysis of DNA damage in individual cells. Methods Cell Biol 64:235–249PubMedCrossRefGoogle Scholar
  113. Ostling O, Johanson KJ (1984) Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun 123(1):291–298PubMedCrossRefGoogle Scholar
  114. Ozmen B et al (2007) Relationship between sperm DNA damage, induced acrosome reaction and viability in ICSI patients. Reprod Biomed Online 15(2):208–214PubMedCrossRefGoogle Scholar
  115. Pasqualotto FF et al (2001) Oxidative stress in normospermic men undergoing infertility evaluation. J Androl 22(2):316–322PubMedGoogle Scholar
  116. Payne JF et al (2005) Redefining the relationship between sperm deoxyribonucleic acid fragmentation as measured by the sperm chromatin structure assay and outcomes of assisted reproductive techniques. Fertil Steril 84(2):356–364PubMedCrossRefGoogle Scholar
  117. Practice Committee of the American Society for Reproductive Medicine (2013) The clinical utility of sperm DNA integrity testing: a guideline. Fertil Steril 99(3):673–677CrossRefGoogle Scholar
  118. Pregl Breznik B, Kovacic B, Vlaisavljevic V (2013) Are sperm DNA fragmentation, hyperactivation, and hyaluronan-binding ability predictive for fertilization and embryo development in in vitro fertilization and intracytoplasmic sperm injection? Fertil Steril 99(5):1233–1241PubMedCrossRefGoogle Scholar
  119. Rama Raju GA et al (2012) Noninsulin-dependent diabetes mellitus: effects on sperm morphological and functional characteristics, nuclear DNA integrity and outcome of assisted reproductive technique. Andrologia 44 Suppl 1:490–498PubMedCrossRefGoogle Scholar
  120. Robinson L et al (2012) The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod 27(10):2908–2917PubMedPubMedCentralCrossRefGoogle Scholar
  121. Sailer BL, Jost LK, Evenson DP (1995) Mammalian sperm DNA susceptibility to in situ denaturation associated with the presence of DNA strand breaks as measured by the terminal deoxynucleotidyl transferase assay. J Androl 16(1):80–87PubMedGoogle Scholar
  122. Saleh RA et al (2002) Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa. Fertil Steril 78(6):1215–1224PubMedCrossRefGoogle Scholar
  123. Saleh RA et al (2003a) Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril 79:1597–1605PubMedCrossRefGoogle Scholar
  124. Saleh RA et al (2003b) Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertil Steril 80(6):1431–1436PubMedCrossRefGoogle Scholar
  125. Sanchez-Martin P et al (2013) Increased pregnancy after reduced male abstinence. Syst Biol Reprod Med 59(5):256–260PubMedCrossRefGoogle Scholar
  126. Seli E et al (2004) Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril 82(2):378–383PubMedCrossRefGoogle Scholar
  127. Sergerie M et al (2005a) Longitudinal study of sperm DNA fragmentation as measured by terminal uridine nick end-labelling assay. Hum Reprod 20(7):1921–1927PubMedPubMedCentralCrossRefGoogle Scholar
  128. Sergerie M et al (2005b) Sperm DNA fragmentation: threshold value in male fertility. Hum Reprod 20(12):3446–3451PubMedCrossRefGoogle Scholar
  129. Shamsi MB, Kumar R, Dada R (2008) Evaluation of nuclear DNA damage in human spermatozoa in men opting for assisted reproduction. Indian J Med Res 127(2):115–123PubMedGoogle Scholar
  130. Sharbatoghli M et al (2012) Relationship of sperm DNA fragmentation, apoptosis and dysfunction of mitochondrial membrane potential with semen parameters and ART outcome after intracytoplasmic sperm injection. Arch Gynecol Obstet 286(5):1315–1322PubMedCrossRefGoogle Scholar
  131. Sikka SC, Rajasekaran M, Hellstrom WJ (1995) Role of oxidative stress and antioxidants in male infertility. J Androl 16(6):464–468PubMedGoogle Scholar
  132. Simon L, Lewis SE (2011) Sperm DNA damage or progressive motility: which one is the better predictor of fertilization in vitro? Syst Biol Reprod Med 57(3):133–138PubMedCrossRefGoogle Scholar
  133. Simon L et al (2010) Clinical significance of sperm DNA damage in assisted reproduction outcome. Hum Reprod 25(7):1594–1608PubMedCrossRefGoogle Scholar
  134. Simon L et al (2011a) Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. Reprod Biomed Online 23(6):724–734PubMedCrossRefGoogle Scholar
  135. Simon L et al (2011b) Sperm DNA damage measured by the alkaline Comet assay as an independent predictor of male infertility and in vitro fertilization success. Fertil Steril 95(2):652–657PubMedCrossRefGoogle Scholar
  136. Simon L et al (2013) Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod Biomed Online 26(1):68–78PubMedCrossRefGoogle Scholar
  137. Simon L et al (2014a) Paternal influence of sperm DNA integrity on early embryonic development. Hum Reprod 29(11):2402–2412PubMedCrossRefGoogle Scholar
  138. Simon L et al (2014b) Comparative analysis of three sperm DNA damage assays and sperm nuclear protein content in couples undergoing assisted reproduction treatment. Hum Reprod 29(5):904–917PubMedCrossRefGoogle Scholar
  139. Simon L et al (2017a) Sperm DNA damage output parameters measured by the alkaline Comet assay and their importance. Andrologia 49(2)Google Scholar
  140. Simon L et al (2017b) A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome. Asian J Androl 19(1):80–90PubMedGoogle Scholar
  141. Singh NP, Stephens RE (1998) X-ray-induced DNA double-strand breaks in human sperm. Mutagenesis 13(1):75–79PubMedCrossRefGoogle Scholar
  142. Singh NP et al (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191PubMedCrossRefGoogle Scholar
  143. Smit M et al (2010) Decreased sperm DNA fragmentation after surgical varicocelectomy is associated with increased pregnancy rate. J Urol 183(1):270–274PubMedPubMedCentralCrossRefGoogle Scholar
  144. Spanò M et al (1998) The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios. Hum Reprod 13(9):2495–2505PubMedCrossRefGoogle Scholar
  145. Spano M et al (2000) Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team. Fertil Steril 73(1):43–50PubMedCrossRefGoogle Scholar
  146. Spano M et al (2005) Exposure to PCB and p, p'-DDE in European and Inuit populations: impact on human sperm chromatin integrity. Hum Reprod 20(12):3488–3499PubMedCrossRefGoogle Scholar
  147. Speyer BE et al (2010) Fall in implantation rates following ICSI with sperm with high DNA fragmentation. Hum Reprod 25(7):1609–1618PubMedCrossRefGoogle Scholar
  148. Stevanato J et al (2008) Semen processing by density gradient centrifugation does not improve sperm apoptotic deoxyribonucleic acid fragmentation rates. Fertil Steril 90(3):889–890PubMedCrossRefGoogle Scholar
  149. Sun JG, Jurisicova A, Casper RF (1997) Detection of deoxyribonucleic acid fragmentation in human sperm: correlation with fertilization in vitro. Biol Reprod 56(3):602–607PubMedPubMedCentralCrossRefGoogle Scholar
  150. Tarozzi N et al (2007) Clinical relevance of sperm DNA damage in assisted reproduction. Reprod Biomed Online 14(6):746–757PubMedCrossRefGoogle Scholar
  151. Tarozzi N et al (2009) Anomalies in sperm chromatin packaging: implications for assisted reproduction techniques. Reprod Biomed Online 18(4):486–495PubMedCrossRefGoogle Scholar
  152. Tavalaee M, Razavi S, Nasr-Esfahani MH (2009) Influence of sperm chromatin anomalies on assisted reproductive technology outcome. Fertil Steril 91(4):1119–1126PubMedCrossRefGoogle Scholar
  153. Tesarik J, Greco E, Mendoza C (2004) Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Hum Reprod 19(3):611–615PubMedCrossRefGoogle Scholar
  154. Thomson LK, Zieschang JA, Clark AM (2011) Oxidative deoxyribonucleic acid damage in sperm has a negative impact on clinical pregnancy rate in intrauterine insemination but not intracytoplasmic sperm injection cycles. Fertil Steril 96(4):843–847PubMedCrossRefGoogle Scholar
  155. Tomsu M, Sharma V, Miller D (2002) Embryo quality and IVF treatment outcomes may correlate with different sperm comet assay parameters. Hum Reprod 17(7):1856–1862PubMedCrossRefGoogle Scholar
  156. Twigg JP, Irvine DS, Aitken RJ (1998) Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplasmic sperm injection. Hum Reprod 13(7):1864–1871PubMedCrossRefGoogle Scholar
  157. Velez de la Calle JF et al (2008) Sperm deoxyribonucleic acid fragmentation as assessed by the sperm chromatin dispersion test in assisted reproductive technology programs: results of a large prospective multicenter study. Fertil Steril 90(5):1792–1799PubMedCrossRefGoogle Scholar
  158. Virro MR, Larson-Cook KL, Evenson DP (2004) Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril 81(5):1289–1295PubMedCrossRefGoogle Scholar
  159. Xia Y et al (2005) Genotoxic effects on spermatozoa of carbaryl-exposed workers. Toxicol Sci 85(1):615–623PubMedCrossRefGoogle Scholar
  160. Yang XY, et al. (2011) [Sperm chromatin structure assay predicts the outcome of intrauterine insemination]. Zhonghua Nan Ke Xue 17(11):977–83Google Scholar
  161. Yang XY, et al. (2013) [Impact of sperm DNA fragmentation index and sperm malformation rate on the clinical outcome of ICSI]. Zhonghua Nan Ke Xue 19(12):1082–1086Google Scholar
  162. Zeyad A et al (2018) Relationships between bacteriospermia, DNA integrity, nuclear protamine alteration, sperm quality and ICSI outcome. Reprod Biol 18(1):115–121CrossRefGoogle Scholar
  163. Zhang X, Gabriel MS, Zini A (2006) Sperm nuclear histone to protamine ratio in fertile and infertile men: evidence of heterogeneous subpopulations of spermatozoa in the ejaculate. J Androl 27(3):414–420PubMedCrossRefGoogle Scholar
  164. Zhao J et al (2014) Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril 102(4):998–1005 e8PubMedPubMedCentralCrossRefGoogle Scholar
  165. Zheng WW et al (2018) Sperm DNA damage has a negative effect on early embryonic development following in vitro fertilization. Asian J Androl 20(1):75–79PubMedCrossRefGoogle Scholar
  166. Zini A, Sigman M (2009) Are tests of sperm DNA damage clinically useful? Pros and cons. J Androl 30(3):219–229PubMedCrossRefGoogle Scholar
  167. Zini A et al (2001) Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil Steril 75(4):674–677PubMedCrossRefGoogle Scholar
  168. Zini A et al (2005) Potential adverse effect of sperm DNA damage on embryo quality after ICSI. Hum Reprod 20(12):3476–3480PubMedCrossRefGoogle Scholar
  169. Zini A et al (2008) Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod 23(12):2663–2668PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Luke Simon
    • 1
  • Benjamin Emery
    • 1
  • Douglas T. Carrell
    • 2
    Email author
  1. 1.Department of Surgery (Urology)University of Utah School of MedicineSalt Lake CityUSA
  2. 2.Andrology and IVF Laboratories, Department of Surgery, and Department of Human GeneticsUniversity of Utah School of MedicineSalt Lake CityUSA

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