Sperm DNA Fragmentation: Treatment Options and Evidence-Based Medicine

  • Ahmad Majzoub
  • Mohamed Arafa
  • Haitham Elbardisi
  • Ashok Agarwal


Sperm DNA fragmentation testing has been recognized as an important additive evaluation tool for examining male fertility potential. This is because SDF can significantly influence fertilization, embryogenesis, and live birth rate. Several indications for SDF testing have been recently recognized. Once detected, the SDF level can aid the clinician in making sound decisions in attempting to normalize the SDF value and improve a man’s fertility status. Treatments such as frequent ejaculations, treatment of infection, avoidance of risk factors, antioxidant therapy, varicocelectomy, sperm selection, and use of testicular sperm for intracytoplasmic sperm injection have been utilized with promising results.


Sperm DNA fragmentation Male infertility Oxidative stress 


  1. 1.
    Kumar N, Singh AK. Trends of male factor infertility, an important cause of infertility: a review of literature. J Hum Reprod Sci. 2015;8(4):191.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Cho CL, Agarwal A. Role of sperm DNA fragmentation in male factor infertility: a systematic review. Arab J Urol. 2018;16(1):21–34.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Zeqiraj A, Beadini S, Beadini N, Aliu H, Gashi Z, Elezaj S, Shabani A. Male infertility and sperm DNA fragmentation. Open Access Maced J Med Sci. 2018;6(8):1342.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Bieniek JM, Lo KC. Recent advances in understanding & managing male infertility. F1000Research. 2016;5:2756.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Pandiyan N, Pandiyan R, Raja DR. A perspective on sperm DNA fragmentation. Transl Androl Urol. 2017;6(Suppl 4):S661.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Malhotra V. Should sperm DNA fragmentation testing be routinely used in assessing male infertility? Transl Androl Urol. 2017;6(Suppl 4):S699.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Agarwal A, Cho CL, Majzoub A, Esteves SC. The society for translational medicine: clinical practice guidelines for sperm DNA fragmentation testing in male infertility. Transl Androl Urol. 2017;6:S720–33.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Loo DT. TUNEL assay. In: In situ detection of DNA damage: Humana Press; 2002. p. 21–30.Google Scholar
  10. 10.
    Beedanagari S, Vulimiri SV, Bhatia S, Mahadevan B. Genotoxicity biomarkers: molecular basis of genetic variability and susceptibility. In: Biomarkers in toxicology: Academic Press; 2014. p. 729–42.CrossRefGoogle Scholar
  11. 11.
    Vandekerckhove FW, De Croo I, Gerris J, Vanden Abbeel E, De Sutter P. Sperm chromatin dispersion test before sperm preparation is predictive of clinical pregnancy in cases of unexplained infertility treated with intrauterine insemination and induction with clomiphene citrate. Front Med. 2016;3:63.CrossRefGoogle Scholar
  12. 12.
    Gosálvez J, López-Fernández C, Fernández JL. Sperm chromatin dispersion test: technical aspects and clinical applications. In: Sperm chromatin. New York, NY: Springer; 2011. p. 151–70.CrossRefGoogle Scholar
  13. 13.
    Fernandez 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.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Evenson DP. Evaluation of sperm chromatin structure and DNA strand breaks is an important part of clinical male fertility assessment. Transl Androl Urol. 2017;6(Suppl 4):S495.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Evenson DP. Sperm chromatin structure assay (SCSA®). In: Spermatogenesis. Totowa, NJ: Humana Press; 2013. p. 147–64.CrossRefGoogle Scholar
  16. 16.
    Cho CL, Esteves SC, Agarwal A. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J Androl. 2016;18(2):186.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Roque M, Esteves SC. Effect of varicocele repair on sperm DNA fragmentation: a review. Int Urol Nephrol. 2018;50(4):583–603.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed Online. 2012;25(3):307–14.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Bungum M, Humaidan P, Axmon A, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22:174–9.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Agarwal A, Cho CL, Esteves SC. Should we evaluate and treat sperm DNA fragmentation? Curr Opin Obstet Gynecol. 2016;28(3):164–71.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Jiang WJ, Jin F, Zhou LM. Influence of the DNA integrity of optimized sperm on the embryonic development and clinical outcomes of in vitro fertilization and embryo transfer. Zhonghua nan ke xue = Natl J Androl. 2016;22(5):425–31.Google Scholar
  22. 22.
    Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, Nelson DR, Thomas AJ. 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(Suppl. 3):1597–605.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kumar K, Deka D, Singh A, Mitra DK, Vanitha BR, Dada R. Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception. J Assist Reprod Genet. 2012;29(9):861–7.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Marmar JL. Is testing of sperm DNA fragmentation (SDF) ready for the basic work-up of male infertility? Transl Androl Urol. 2017;6(Suppl 4):S437.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    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.CrossRefGoogle Scholar
  26. 26.
    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.CrossRefGoogle Scholar
  27. 27.
    Zhao J, Zhang Q, Wang Y, Li Y. 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. 2014;102(4):998–1005.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Zini A, Sigman M. Are tests of sperm DNA damage clinically useful? Pros and cons. J Androl. 2009 May-Jun;30(3):219–29.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Anifandis G, Bounartzi T, Messini CI, Dafopoulos K, Sotiriou S, Messinis IE. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    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.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Gosálvez J, González-Martínez M, López-Fernández C, Fernández JL, Sánchez-Martín P. Shorter abstinence decreases sperm deoxyribonucleic acid fragmentation in ejaculate. Fertil Steril. 2011;96(5):1083–6.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Agarwal A, Gupta S, du Plessis S, Sharma R, Esteves SC, Cirenza C, et al. Abstinence time and its impact on basic and advanced semen parameters. Urology. 2016;94:102–10.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Kim GY. What should be done for men with sperm DNA fragmentation? Clin Exp Reprod Med. 2018;45(3):101–9.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Majzoub A, Agarwal A, Esteves SC. Antioxidants for elevated sperm DNA fragmentation: a mini review. Transl Androl Urol. 2017;6(Suppl 4):S649.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Atig F, Raffa M, Habib BA, Kerkeni A, Saad A, Ajina M. Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men. BMC Urol. 2012;12(1):6.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Sagayan E, Acacio B, Coulam C, Sher G, Nouriani M. Effects of antioxidant treatment on DNA fragmentation index. Fertil Steril. 2004;82:S88.CrossRefGoogle Scholar
  37. 37.
    Abad C, Amengual MJ, Gosálvez J, Coward K, Hannaoui N, Benet J, et al. Effects of oral antioxidant treatment upon the dynamics of human sperm DNA fragmentation and subpopulations of sperm with highly degraded DNA. Andrologia. 2013;45(3):211–6.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Martínez-Soto JC, Domingo JC, Cordobilla B, Nicolás M, Fernández L, Albero P, et al. Dietary supplementation with docosahexaenoic acid (DHA) improves seminal antioxidant status and decreases sperm DNA fragmentation. Syst Biol Reprod Med. 2016;62(6):387–95.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Ng CM, Blackman MR, Wang C, Swerdloff RS. The role of carnitine in the male reproductive system. Ann N Y Acad Sci. 2004;1033(1):177–88.PubMedCrossRefGoogle Scholar
  40. 40.
    Gual-Frau J, Abad C, Amengual MJ, Hannaoui N, Checa MA, Ribas-Maynou J, et al. Oral antioxidant treatment partly improves integrity of human sperm DNA in infertile grade I varicocele patients. Hum Fertil. 2015;18(3):225–9.CrossRefGoogle Scholar
  41. 41.
    Filipcikova R, Oborna I, Brezinova J, Novotny J, Wojewodka G, De Sanctis JB, et al. Lycopene improves the distorted ratio between AA/DHA in the seminal plasma of infertile males and increases the likelihood of successful pregnancy. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015;159(1):77–82.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Chan P. Management options of varicoceles. Indian J Urol. 2011;27(1):65.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Raheem OA. Surgical management of adolescent varicocele: systematic review of the world literature. Urol Ann. 2013;5(3):133.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Practice Committee of the American Society for Reproductive Medicine. Report on varicocele and infertility. Fertil Steril. 2008;90(5):S247–9.CrossRefGoogle Scholar
  45. 45.
    Cho KS, Seo JT. Effect of varicocelectomy on male infertility. Korean J Urol. 2014;55(11):703–9.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Wang YJ, Zhang RQ, Lin YJ, Zhang RG, Zhang WL. Relationship between varicocele and sperm DNA damage and the effect of varicocele repair: a meta-analysis. Reprod Biomed Online. 2012;25(3):307–14.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Montag M, Toth B, Strowitzki T. Sperm selection in ART. Journal für Reproduktionsmedizin und Endokrinologie-J Reprod Med Endocrinol. 2012;9(6):485–9.Google Scholar
  48. 48.
    Beydola T, Sharma RK, Lee W, Agarwal A, Rizk B, Aziz N, Agarwal A. Sperm preparation and selection techniques. In: Male infertility practice. New Delhi: Jaypee Brothers Medical Publishers; 2013. p. 244–51.Google Scholar
  49. 49.
    Parmegiani L, Cognigni GE, Bernardi S, et al. “Physiologic ICSI”: hyaluronic acid (HA) favors selection of spermatozoa without DNA fragmentation and with normal nucleus, resulting in improvement of embryo quality. Fertil Steril. 2010;93:598–604.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Rashki Ghaleno L, Rezazadeh Valojerdi M, Chehrazi M, et al. Hyaluronic acid binding assay is highly sensitive to select human spermatozoa with good progressive motility, morphology, and nuclear Maturity. Gynecol Obstet Investig. 2016;81:244–50.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Hammoud I, Boitrelle F, Ferfouri F, et al. Selection of normal spermatozoa with a vacuole-free head (x6300) improves selection of spermatozoa with intact DNA in patients with high sperm DNA fragmentation rates. Andrologia. 2013;45:163–70.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Maettner R, Sterzik K, Isachenko V, et al. Quality of human spermatozoa: relationship between high-magnification sperm morphology and DNA integrity. Andrologia. 2014;46:547–55.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Enciso M, Iglesias M, Galán I, Sarasa J, Gosálvez A, Gosálvez J. The ability of sperm selection techniques to remove single-or double-strand DNA damage. Asian J Androl. 2011;13(5):764.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Esteves SC, Agarwal A, Majzoub A. Comparison of strategies to reduce sperm DNA fragmentation in couples undergoing ICSI. Transl Androl Urol. 2017;6(Suppl 4):S570.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Moskovtsev SI, Jarvi K, Mullen JB, et al. Testicular spermatozoa have statistically significantly lower DNA damage compared with ejaculated spermatozoa in patients with unsuccessful oral antioxidant treatment. Fertil Steril. 2010;93:1142–6.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Greco E, Scarselli F, Lacobelli M, et al. Efficient treatment of infertility due to sperm DNA damage by ICSI with testicular spermatozoa. Hum Reprod. 2005;20:226–30.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Arafa M, AlMalki A, AlBadr M, Burjaq H, Majzoub A, AlSaid S, Elbardisi H. ICSI outcome in patients with high DNA fragmentation: testicular versus ejaculated spermatozoa. Andrologia. 2018;50(1)CrossRefGoogle Scholar
  58. 58.
    Esteves SC, Roque M, Bradley CK, Garrido N. Reproductive outcomes of testicular versus ejaculated sperm for intracytoplasmic sperm injection among men with high levels of DNA fragmentation in semen: systematic review and meta-analysis. Fertil Steril. 2017;108(3):456–67.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Agarwal A, Cho CL, Majzoub A, Esteves S. Expanding treatment paradigm of high sperm DNA fragmentation. Transl Androl Urol. 2017;6(4):S450–2.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • Ahmad Majzoub
    • 1
  • Mohamed Arafa
    • 1
  • Haitham Elbardisi
    • 1
  • Ashok Agarwal
    • 2
  1. 1.Department of UrologyHamad Medical CorporationDohaQatar
  2. 2.Cleveland ClinicClevelandUSA

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