SpringerLink
Log in

Sperm DNA Fragmentation and Male Infertility

  • Chapter
  • First Online:
Genetics of Male Infertility

Abstract

Sperm DNA fragmentation (SDF) is associated with male infertility, and it adversely affects reproductive outcomes. Both chromatin integrity and protamination status determine the extent of DNA damage. Oxidative stress due to increased levels of reactive oxygen species in the seminal fluid damages sperm DNA. Several tests have been introduced into the clinical laboratory settings to assess the sperm chromatin integrity and the extent of SDF. This chapter elucidates the molecular changes, specifically proteomic alterations, caused due to SDF. Moreover, the factors affecting sperm DNA integrity and the consequences of increased SDF are highlighted. It also focusses on the importance of SDF testing and its impact on reproductive outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free ship** worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Fleming S, Green S, Hall J, Hunter A. Analysis and alleviation of male infertility. Microsc Anal. 1995;45:35–7.

    Google Scholar 

  2. Neri Q, Tanaka N, Wang A, Katagiri Y, Takeuchi T, Rosenwaks Z, et al. Intracytoplasmic sperm injection. Minerva Ginecol. 2004;56:189–96.

    CAS  PubMed  Google Scholar 

  3. Al Omrani B, Al Eisa N, Javed M, Al Ghedan M, Al Matrafi H, Al Sufyan H. Associations of sperm DNA fragmentation with lifestyle factors and semen parameters of Saudi men and its impact on ICSI outcome. Reprod Biol Endocrinol. 2018;16(1):49.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. González-Marín C, Gosálvez J, Roy R. Types, causes, detection and repair of DNA fragmentation in animal and human sperm cells. Int J Mol Sci. 2012;13(11):14026–52.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Jarrow J, Sigman M, Kolettis PN, Lipshultz LR, McClure RD, et al. Optimal evaluation of the infertile male. AUA best practice statement reviewed and validity confirmed. 2011.

    Google Scholar 

  6. Male infertility. EAU guidelines [Internet]. 2017 [cited September, 2018]. Available from: https://uroweb.org/guideline/male-infertility/.

  7. Conwell CC, Vilfan ID, Hud NV. Controlling the size of nanoscale toroidal DNA condensates with static curvature and ionic strength. Proc Natl Acad Sci. 2003;100(16):9296–301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Simon L, Aston K, Emery B, Hotaling J, Carrell D. Sperm DNA damage output parameters measured by the alkaline comet assay and their importance. Andrologia. 2017;49(2):e12608.

    Article  CAS  Google Scholar 

  9. Simon L, Murphy K, Shamsi M, Liu L, Emery B, Aston K, et al. Paternal influence of sperm DNA integrity on early embryonic development. Hum Reprod. 2014;29(11):2402–12.

    Article  CAS  PubMed  Google Scholar 

  10. Ward WS. Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod. 2009;16(1):30–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Ajduk A, Yamauchi Y, Ward MA. Sperm chromatin remodeling after intracytoplasmic sperm injection differs from that of in vitro fertilization. Biol Reprod. 2006;75(3):442–51.

    Article  CAS  PubMed  Google Scholar 

  12. Page AW, Orr-Weaver TL. Stop** and starting the meiotic cell cycle. Curr Opin Genet Dev. 1997;7(1):23–31.

    Article  CAS  PubMed  Google Scholar 

  13. Erenpreiss J, Spano M, Erenpreisa J, Bungum M, Giwercman A. Sperm chromatin structure and male fertility: biological and clinical aspects. Asian J Androl. 2006;8(1):11–29.

    Article  CAS  PubMed  Google Scholar 

  14. Laberge R-M, Boissonneault G. On the nature and origin of DNA strand breaks in elongating spermatids. Biol Reprod. 2005;73(2):289–96.

    Article  CAS  PubMed  Google Scholar 

  15. Erenpreiss J, Bars J, Lipatnikova V, Erenpreisa J, Zalkalns J. Comparative study of cytochemical tests for sperm chromatin integrity. J Androl. 2001;22(1):45–53.

    CAS  PubMed  Google Scholar 

  16. González-Rojo S, Fernández-Díez C, Guerra SM, Robles V, Herraez MP. Differential gene susceptibility to sperm DNA damage: analysis of developmental key genes in trout. PLoS One. 2014;9(12):e114161.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Gunes S, Al-Sadaan M, Agarwal A. Spermatogenesis, DNA damage and DNA repair mechanisms in male infertility. Reprod Biomed Online. 2015;31(3):309–19.

    Article  CAS  PubMed  Google Scholar 

  18. Ahmad G, Agarwal A. Ionizing radiation and male fertility. In: Male infertility: Springer, New Delhi; 2017. p. 185–96.

    Google Scholar 

  19. Henkel R, Kierspel E, Stalf T, Mehnert C, Menkveld R, Tinneberg H-R, et al. Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients. Fertil Steril. 2005;83(3):635–42.

    Article  CAS  PubMed  Google Scholar 

  20. Sakkas D, Mariethoz E, Manicardi G, Bizzaro D, Bianchi PG, Bianchi U. Origin of DNA damage in ejaculated human spermatozoa. Rev Reprod. 1999;4(1):31–7.

    Article  CAS  PubMed  Google Scholar 

  21. Sakkas D, Manicardi G, Grace Bianchi P, Bizzaro D, Bianchi U. Relationship between the presence of endogenous nicks and sperm chromatin packaging in maturing and fertilizing mouse spermatozoa. Biol Reprod. 1995;52(5):1149–55.

    Article  CAS  PubMed  Google Scholar 

  22. Esteves SC, Sánchez-Martín F, Sánchez-Martín P, Schneider DT, Gosálvez J. Comparison of reproductive outcome in oligozoospermic men with high sperm DNA fragmentation undergoing intracytoplasmic sperm injection with ejaculated and testicular sperm. Fertil Steril. 2015;104(6):1398–405.

    Article  PubMed  Google Scholar 

  23. John Aitken R, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod. 1989;41(1):183–97.

    Article  Google Scholar 

  24. Sakamoto Y, Ishikawa T, Kondo Y, Yamaguchi K, Fujisawa M. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 2008;101(12):1547–52.

    Article  CAS  PubMed  Google Scholar 

  25. Hamada A, Esteves SC, Agarwal A. Insight into oxidative stress in varicocele-associated male infertility: part 2. Nat Rev Urol. 2013;10(1):26–37.

    Article  CAS  PubMed  Google Scholar 

  26. Wang Y-J, Zhang R-Q, Lin Y-J, Zhang R-G, Zhang W-L. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed Online. 2012;25(3):307–14.

    Article  CAS  PubMed  Google Scholar 

  27. Intasqui P, Camargo M, Del Giudice PT, Spaine DM, Carvalho VM, Cardozo KHM, et al. Sperm nuclear DNA fragmentation rate is associated with differential protein expression and enriched functions in human seminal plasma. BJU Int. 2013;112(6):835–43.

    Article  CAS  PubMed  Google Scholar 

  28. Intasqui P, Camargo M, Del Giudice PT, Spaine DM, Carvalho VM, Cardozo KHM, et al. Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation. J Assist Reprod Genet. 2013;30(9):1187–202.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Skowronek F, Casanova G, Alciaturi J, Capurro A, Cantu L, Montes JM, et al. DNA sperm damage correlates with nuclear ultrastructural sperm defects in teratozoospermic men. Andrologia. 2012;44(1):59–65.

    Article  CAS  PubMed  Google Scholar 

  30. Puga Molina LC, Luque GM, Balestrini PA, Marín-Briggiler CI, Romarowski A, Buffone MG. Molecular basis of human sperm capacitation. Front Cell Dev Biol. 2018;6:72.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Guraya SS. Cellular and molecular biology of capacitation and acrosome reaction in spermatozoa. Int Rev Cytol. 2000;199:1–64.

    Article  CAS  PubMed  Google Scholar 

  32. Intasqui P, Camargo M, Del Giudice PT, Spaine DM, Carvalho VM, Cardozo KH, et al. Sperm nuclear DNA fragmentation rate is associated with differential protein expression and enriched functions in human seminal plasma. BJU Int. 2013;112(6):835–43.

    Article  CAS  PubMed  Google Scholar 

  33. Behrouzi B, Kenigsberg S, Alladin N, Swanson S, Zicherman J, Hong S-H, et al. Evaluation of potential protein biomarkers in patients with high sperm DNA damage. Syst Biol Reprod Med. 2013;59(3):153–63.

    Article  CAS  PubMed  Google Scholar 

  34. Intasqui P, Camargo M, Antoniassi MP, Cedenho AP, Carvalho VM, Cardozo KHM, et al. Association between the seminal plasma proteome and sperm functional traits. Fertil Steril. 2016;105(3):617–28.

    Article  CAS  PubMed  Google Scholar 

  35. Antoniassi MP, Intasqui P, Camargo M, Zylbersztejn DS, Carvalho VM, Cardozo KH, et al. Analysis of the functional aspects and seminal plasma proteomic profile of sperm from smokers. BJU Int. 2016;118(5):814–22.

    Article  CAS  PubMed  Google Scholar 

  36. Sharma R, Agarwal A, Mohanty G, Du Plessis SS, Gopalan B, Willard B, et al. Proteomic analysis of seminal fluid from men exhibiting oxidative stress. Reprod Biol Endocrinol. 2013;11:85.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Cho C-L, Agarwal A. Role of sperm DNA fragmentation in male factor infertility: a systematic review. Arab J Urol. 2018;16(1):21–34.

    Article  PubMed  Google Scholar 

  38. Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, et al. Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril. 2003;79:1597–605.

    Article  PubMed  Google Scholar 

  39. Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79(4):829–43.

    Article  PubMed  Google Scholar 

  40. Sakkas D, Urner F, Bizzaro D, Manicardi G, Bianchi P, Shoukir Y, et al. Sperm nuclear DNA damage and altered chromatin structure: effect on fertilization and embryo development. Hum Reprod. 1998;13(suppl_4):11–9.

    Article  PubMed  Google Scholar 

  41. Avendaño C, Franchi A, Taylor S, Morshedi M, Bocca S, Oehninger S. Fragmentation of DNA in morphologically normal human spermatozoa. Fertil Steril. 2009;91(4):1077–84.

    Article  PubMed  Google Scholar 

  42. Avendaño C, Franchi A, Duran H, Oehninger S. DNA fragmentation of normal spermatozoa negatively impacts embryo quality and intracytoplasmic sperm injection outcome. Fertil Steril. 2010;94(2):549–57.

    Article  PubMed  Google Scholar 

  43. Saleh RA, Agarwal A, Nelson DR, Nada EA, El-Tonsy MH, Alvarez JG, et al. Increased sperm nuclear DNA damage in normozoospermic infertile men: a prospective study. Fertil Steril. 2002;78(2):313–8.

    Article  PubMed  Google Scholar 

  44. Agarwal A, Cho C-L, Majzoub A, Esteves SC. The role of female factors in the management of sperm DNA fragmentation. Transl Androl Urol. 2017;6(Suppl 4):S488.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Engel W, Sancken U, Laccone F. Paternal age from a genetic point of view. J Reproduktionsmed Endokrinol. 2004;1:263–7.

    Google Scholar 

  46. Alshahrani S, Agarwal A, Assidi M, Abuzenadah AM, Durairajanayagam D, Ayaz A, et al. Infertile men older than 40 years are at higher risk of sperm DNA damage. Reprod Biol Endocrinol. 2014;12(1):103.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Winkle T, Rosenbusch B, Gagsteiger F, Paiss T, Zoller N. The correlation between male age, sperm quality and sperm DNA fragmentation in 320 men attending a fertility center. J Assist Reprod Genet. 2009;26(1):41–6.

    Article  PubMed  Google Scholar 

  48. Brahem S, Mehdi M, Elghezal H, Saad A. The effects of male aging on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population. J Assist Reprod Genet. 2011;28(5):425–32.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Luetjens C, Rolf C, Gassner P, Werny J, Nieschlag E. Sperm aneuploidy rates in younger and older men. Hum Reprod. 2002;17(7):1826–32.

    Article  CAS  PubMed  Google Scholar 

  50. Loft S, Poulsen HE. Cancer risk and oxidative DNA damage in man. J Mol Med. 1996;74(6):297–312.

    Article  CAS  PubMed  Google Scholar 

  51. Agarwal A, Sengupta P, Durairajanayagam D. Role of L-carnitine in female infertility. Reprod Biol Endocrinol. 2018;16(1):5.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Ahmadi S, Bashiri R, Ghadiri-Anari A, Nadjarzadeh A. Antioxidant supplements and semen parameters: an evidence based review. Int J Reprod Biomed. 2016;14(12):729.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005;26(3):349–53.

    Article  CAS  PubMed  Google Scholar 

  54. Cui X, **g X, Wu X, Wang Z, Li Q. Potential effect of smoking on semen quality through DNA damage and the downregulation of Chk1 in sperm. Mol Med Rep. 2016;14(1):753–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Akang EN, Oremosu AA, Osinubi AA, James AB, Biose IJ, Dike SI, et al. Alcohol-induced male infertility: is sperm DNA fragmentation a causative? J Exp Clin Anatomy. 2017;16(1):53.

    Google Scholar 

  56. Anifandis G, Bounartzi T, Messini C, Dafopoulos K, Sotiriou S, Messinis I. The impact of cigarette smoking and alcohol consumption on sperm parameters and sperm DNA fragmentation (SDF) measured by Halosperm®. Arch Gynecol Obstet. 2014;290(4):777–82.

    Article  CAS  PubMed  Google Scholar 

  57. De Iuliis GN, Thomson LK, Mitchell LA, Finnie JM, Koppers AJ, Hedges A, et al. DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2′-deoxyguanosine, a marker of oxidative stress. Biol Reprod. 2009;81(3):517–24.

    Article  PubMed  CAS  Google Scholar 

  58. Mitchell L, De Iuliis G, Aitken RJ. The TUNEL assay consistently underestimates DNA damage in human spermatozoa and is influenced by DNA compaction and cell vitality: development of an improved methodology. Int J Androl. 2011;34(1):2–13.

    Article  CAS  PubMed  Google Scholar 

  59. Dupont C, Faure C, Sermondade N, Boubaya M, Eustache F, Clément P, et al. Obesity leads to higher risk of sperm DNA damage in infertile patients. Asian J Androl. 2013;15(5):622.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Bakos H, Mitchell M, Setchell B, Lane M. The effect of paternal diet‐induced obesity on sperm function and fertilization in a mouse model. Int J Androl. 2011;34(5pt1):402–10.

    Article  CAS  PubMed  Google Scholar 

  61. Palmer NO, Bakos HW, Fullston T, Lane M. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis. 2012;2(4):253–63.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Sengupta P. Environmental and occupational exposure of metals and their role in male reproductive functions. Drug Chem Toxicol. 2013;36(3):353–68.

    Article  CAS  PubMed  Google Scholar 

  63. Sengupta P, Banerjee R. Environmental toxins: alarming impacts of pesticides on male fertility. Hum Exp Toxicol. 2014;33(10):1017–39.

    Article  PubMed  CAS  Google Scholar 

  64. Jeng HA. Exposure to endocrine disrupting chemicals and male reproductive health. Front Public Health. 2014;2:55.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Evenson DP, Wixon R. Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm Chromatin Structure Assay (SCSA®). Toxicol Appl Pharmacol. 2005;207(2):532–7.

    Article  PubMed  CAS  Google Scholar 

  66. Agarwal A, Deepinder F, Sharma RK, Ranga G, Li J. Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertil Steril. 2008;89(1):124–8.

    Article  PubMed  Google Scholar 

  67. Morris ID. Sperm DNA damage and cancer treatment 1. Int J Androl. 2002;25(5):255–61.

    Article  CAS  PubMed  Google Scholar 

  68. Smit M, Van Casteren N, Wildhagen M, Romijn J, Dohle G. Sperm DNA integrity in cancer patients before and after cytotoxic treatment. Hum Reprod. 2010;25(8):1877–83.

    Article  CAS  PubMed  Google Scholar 

  69. Ochsendorf F. Infections in the male genital tract and reactive oxygen species. Hum Reprod Update. 1999;5(5):399–420.

    Article  CAS  PubMed  Google Scholar 

  70. Gallegos G, Ramos B, Santiso R, Goyanes V, Gosálvez J, Fernández JL. Sperm DNA fragmentation in infertile men with genitourinary infection by chlamydia trachomatis and mycoplasma. Fertil Steril. 2008;90(2):328–34.

    Article  PubMed  Google Scholar 

  71. Erenpreiss J, Hlevicka S, Zalkalns J, Erenpreisa J. Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal semen samples. J Androl. 2002;23(5):717–23.

    PubMed  Google Scholar 

  72. Majzoub A, Agarwal A, Cho CL, Esteves SC. Sperm DNA fragmentation testing: a cross sectional survey on current practices of fertility specialists. Transl Androl Urol. 2017;6(Suppl 4):S710–9.

    Article  PubMed  PubMed Central  Google Scholar 

  73. AUGER J, MESBAH M, HUBER C, DADOUNE JP. Aniline blue staining as a marker of sperm chromatin defects associated with different semen characteristics discriminates between proven fertile and suspected infertile men. Int J Androl. 1990;13(6):452–62.

    Article  CAS  PubMed  Google Scholar 

  74. Manicardi GC, Bizzaro D, Basic SD. Clinical aspects of sperm chromomycin A3 assay. In: Zini A, Agarwal A, editors. Sperm chromatin: biological and clinical applications in male infertility and assisted reproduction. New York: Springer New York; 2011. p. 171–9.

    Chapter  Google Scholar 

  75. Manicardi GC, Bianchi PG, Pantano S, Azzoni P, Bizzaro D, Bianchi U, et al. Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility1. Biol Reprod. 1995;52(4):864–7.

    Article  CAS  PubMed  Google Scholar 

  76. Sakkas D, Urner F, Bizzaro D, Manicardi G, Bianchi PG, Shoukir Y, et al. Sperm nuclear DNA damage and altered chromatin structure: effect on fertilization and embryo development. Hum Reprod. 1998;13(suppl_4):11–9.

    Article  PubMed  Google Scholar 

  77. Evenson DP. The Sperm Chromatin Structure Assay (SCSA®) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Anim Reprod Sci. 2016;169:56–75.

    Article  CAS  PubMed  Google Scholar 

  78. Evenson DP, LARSON KL, Jost LK. Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Androl. 2002;23(1):25–43.

    Article  PubMed  Google Scholar 

  79. Evenson DP. Sperm Chromatin Structure Assay (SCSA®): 30 years of experience with the SCSA®. In: Sperm chromatin: Springer, New York, NY; 2011. p. 125–49.

    Chapter  Google Scholar 

  80. Fernández JL, Muriel L, Goyanes V, Segrelles E, Gosálvez J, Enciso M, et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertil Steril. 2005;84(4):833–42.

    Article  PubMed  CAS  Google Scholar 

  81. Fernández JL, Muriel L, Rivero MT, Goyanes V, Vazquez R, Alvarez JG. The sperm chromatin dispersion test: a simple method for the determination of sperm DNA fragmentation. J Androl. 2003;24(1):59–66.

    PubMed  Google Scholar 

  82. Pratap H, Hottigoudar SY, Nichanahalli KS, Chand P. Assessment of sperm deoxyribose nucleic acid fragmentation using sperm chromatin dispersion assay. J Pharmacol Pharmacother. 2017;8(2):45–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ostling O, Johanson KJ. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commun. 1984;123(1):291–8.

    Article  CAS  PubMed  Google Scholar 

  84. Singh NP, Danner DB, Tice RR, McCoy MT, Collins GD, Schneider EL. Abundant alkali-sensitive sites in DNA of human and mouse sperm. Exp Cell Res. 1989;184(2):461–70.

    Article  CAS  PubMed  Google Scholar 

  85. Sharma R, Masaki J, Agarwal A. Sperm DNA fragmentation analysis using the TUNEL assay. Methods Mol Biol 2013;927:121–36.

    Google Scholar 

  86. Gupta S, Sharma R, Agarwal A. Inter‐and intra‐laboratory standardization of TUNEL assay for assessment of sperm DNA fragmentation. Curr Protoc Toxicol. 2017;74(1):16.1. 1-.1. 22.

    Article  CAS  Google Scholar 

  87. Mahfouz RZ, Said TM, Agarwal A. The diagnostic and therapeutic applications of flow cytometry in male infertility. Arch Med Sci Spec Issues. 2009;2009(1):108.

    Google Scholar 

  88. Sharma R, Cakar Z, Agarwal A. TUNEL assay by benchtop flow cytometer in clinical laboratories. In: A Clinician’s guide to sperm DNA and chromatin damage: Springer, Cham; 2018. p. 103–18.

    Chapter  Google Scholar 

  89. Sharma RK, Sabanegh E, Mahfouz R, Gupta S, Thiyagarajan A, Agarwal A. TUNEL as a test for sperm DNA damage in the evaluation of male infertility. Urology. 2010;76(6):1380–6.

    Article  PubMed  Google Scholar 

  90. Sharma R, Ahmad G, Esteves SC, Agarwal A. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay using bench top flow cytometer for evaluation of sperm DNA fragmentation in fertility laboratories: protocol, reference values, and quality control. J Assist Reprod Genet. 2016;33(2):291–300.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Ribeiro S, Sharma R, Gupta S, Cakar Z, De Geyter C, Agarwal A. Inter‐and intra‐laboratory standardization of TUNEL assay for assessment of sperm DNA fragmentation. Andrology. 2017;5(3):477–85.

    Article  CAS  PubMed  Google Scholar 

  92. Moskovtsev SI, Jarvi K, Mullen JBM, Cadesky KI, Hannam T, Lo KC. Testicular spermatozoa have statistically significantly lower DNA damage compared with ejaculated spermatozoa in patients with unsuccessful oral antioxidant treatment. Fertil Steril. 2010;93(4):1142–6.

    Article  CAS  PubMed  Google Scholar 

  93. Greco E, Scarselli F, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, et al. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod. 2005;20(1):226–30.

    Article  PubMed  Google Scholar 

  94. Esteves SC, Agarwal A, Cho C-L, Majzoub A. A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios. Transl Androl Urol. 2017;6(Suppl 4):S734.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Spanò M, Bonde JP, Hjøllund HI, Kolstad HA, Cordelli E, Leter G, et al. Sperm chromatin damage impairs human fertility. Fertil Steril. 2000;73(1):43–50.

    Article  PubMed  Google Scholar 

  96. Muriel L, Meseguer M, Fernández JL, Alvarez J, Remohí J, Pellicer A, et al. Value of the sperm chromatin dispersion test in predicting pregnancy outcome in intrauterine insemination: a blind prospective study. Hum Reprod. 2005;21(3):738–44.

    Article  PubMed  Google Scholar 

  97. Duran EH, Morshedi M, Taylor S, Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod. 2002;17(12):3122–8.

    Article  CAS  PubMed  Google Scholar 

  98. Rilcheva VS, Ayvazova NP, Ilieva LO, Ivanova SP, Konova EI. Sperm DNA integrity test and assisted reproductive technology (art) outcome. J Biomed Clin Res. 2016;9(1):21–9.

    Article  Google Scholar 

  99. Cissen M, van Wely M, Scholten I, Mansell S, de Bruin JP, Mol BW, et al. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PLoS One. 2016;11(11):e0165125.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Simon L, Brunborg G, Stevenson M, Lutton D, McManus J, Lewis SE. Clinical significance of sperm DNA damage in assisted reproduction outcome. Hum Reprod. 2010;25(7):1594–608.

    Article  CAS  PubMed  Google Scholar 

  101. Morris ID. Sperm DNA damage and cancer treatment. Int J Androl. 2002;25(5):255–61.

    Article  CAS  PubMed  Google Scholar 

  102. Virro M, Evenson D. Sperm chromatin structure assay (SCSA®) related to blastocyst rate, pregnancy rate, and spontaneous abortion in IVF and ICSI cycles. Fertil Steril. 2003;79:16.

    Article  Google Scholar 

  103. Mohammad HN-E, Mohammad S, Shahnaz R, Maryam A, Shahla R, Fariba M, et al. Effect of sperm DNA damage and sperm protamine deficiency on fertilization and embryo development post-ICSI. Reprod Biomed Online. 2005;11(2):198–205.

    Article  Google Scholar 

  104. Simon L, Proutski I, Stevenson M, Jennings D, McManus J, Lutton D, et al. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod Biomed Online. 2013;26(1):68–78.

    Article  CAS  PubMed  Google Scholar 

  105. Osman A, Alsomait H, Seshadri S, El-Toukhy T, Khalaf Y. The effect of sperm DNA fragmentation on live birth rate after IVF or ICSI: a systematic review and meta-analysis. Reprod Biomed Online. 2015;30(2):120–7.

    Article  CAS  PubMed  Google Scholar 

  106. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012;27(10):2908–17.

    Article  CAS  PubMed  Google Scholar 

  107. Panner Selvam MK, Agarwal A. A systemic review on sperm DNA fragmentation in male factor infertility: laboratory assessment. Arab J Urol. 2018;16(1):65–76.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA

    Manesh Kumar Panner Selvam & Ashok Agarwal

  2. Department of Physiology, Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jenjarom, Selangor, Malaysia

    Pallav Sengupta

Authors
  1. Manesh Kumar Panner Selvam
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pallav Sengupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashok Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashok Agarwal .

Editor information

Editors and Affiliations

  1. Department of Urology, Hamad Medical Corporation, Doha, Qatar

    Mohamed Arafa

  2. Department of Urology, Hamad Medical Corporation, Doha, Qatar

    Haitham Elbardisi

  3. Department of Urology, Hamad Medical Corporation, Doha, Qatar

    Ahmad Majzoub

  4. Cleveland Clinic, Cleveland, OH, USA

    Ashok Agarwal

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Panner Selvam, M.K., Sengupta, P., Agarwal, A. (2020). Sperm DNA Fragmentation and Male Infertility. In: Arafa, M., Elbardisi, H., Majzoub, A., Agarwal, A. (eds) Genetics of Male Infertility. Springer, Cham. https://doi.org/10.1007/978-3-030-37972-8_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-37972-8_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-37971-1

  • Online ISBN: 978-3-030-37972-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation