Is sperm dna damage associated with IVF embryo quality? A systematic review

  • Armand Zini
  • Wael Jamal
  • Lisa Cowan
  • Naif Al-Hathal
Gamete Biology



Sperm DNA damage is common amongst infertile men and may adversely impact natural reproduction, IUI-assisted reproduction and to a lesser degree IVF pregnancy. The objective of this study was to examine the influence of sperm DNA damage on embryo quality and/or development at IVF and ICSI.


We conducted a systematic review of studies that evaluated sperm DNA damage and embryo development and/or quality after IVF and/or ICSI.


We identified 28 studies (8 IVF, 12 ICSI and 8 mixed IVF-ICSI studies) that evaluated the relationship between sperm DNA damage and embryo quality. These 28 studies evaluated 3226 treatment cycles (1033 IVF and 873 ICSI, 1320 mixed IVF-ICSI cycles) and demonstrated highly variable characteristics. In 11 of the 28 studies (1/8 IVF, 5/12 ICSI and 5/8 mixed IVF-ICSI studies), sperm DNA damage was associated with poor embryo quality and/or development, whereas the remaining 17 studies showed no relationship between sperm DNA damage and embryo quality and/or development.


This systematic review indicates that the evaluable studies are heterogeneous and that overall, there is no consistent relationship between sperm DNA damage and embryo quality and/or development. The data also suggest that the influence of sperm DNA damage on embryo quality/development may be more significant in ICSI compared to IVF cycles.


Spermatozoa Sperm DNA Embryo Pregnancy In vitro fertilization 


  1. 1.
    Ahmadi A, Ng SC. Fertilizing ability of DNA-damaged spermatozoa. J Exp Zool. 1999;284:696–704.PubMedCrossRefGoogle Scholar
  2. 2.
    Avendano C, Franchi A, Duran H, Oehninger S. DNA fragmentation of normal spermatozoa negatively impacts embryo quality and intracytoplasmic sperm injection outcome. Fertil Steril. 2009a.Google Scholar
  3. 3.
    Avendano C, Franchi A, Taylor S, Morshedi M, Bocca S, Oehninger S. Fragmentation of DNA in morphologically normal human spermatozoa. Fertil Steril. 2009;91:1077–84.PubMedCrossRefGoogle Scholar
  4. 4.
    Baart EB, Martini E, Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, et al. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007;22:980–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Barratt CL, Aitken RJ, Bjorndahl L, Carrell DT, De Boer P, Kvist U, et al. Sperm DNA: organization, protection and vulnerability: from basic science to clinical applications--a position report. Hum Reprod. 25:824–38.Google Scholar
  6. 6.
    Benchaib M, Lornage J, Mazoyer C, Lejeune H, Salle B, Francois Guerin J. Sperm deoxyribonucleic acid fragmentation as a prognostic indicator of assisted reproductive technology outcome. Fertil Steril. 2007;87:93–100.PubMedCrossRefGoogle Scholar
  7. 7.
    Boe-Hansen GB, Fedder J, Ersboll AK, Christensen P. The sperm chromatin structure assay as a diagnostic tool in the human fertility clinic. Hum Reprod. 2006;21:1576–82.PubMedCrossRefGoogle Scholar
  8. 8.
    Borini A, Tarozzi N, Bizzaro D, Bonu MA, Fava L, Flamigni C, et al. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006;21:2876–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Braude P, Bolton V, Moore S. Human gene expression first occurs between the four- and eight-cell stages of preimplantation development. Nature. 1988;332:459–61.PubMedCrossRefGoogle Scholar
  10. 10.
    Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22:174–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Carrell DT, Hammoud SS. The human sperm epigenome and its potential role in embryonic development. Mol Hum Reprod. 2010;16:37–47.PubMedCrossRefGoogle Scholar
  12. 12.
    Check JH, Graziano V, Cohen R, Krotec J, Check ML. Effect of an abnormal sperm chromatin structural assay (SCSA) on pregnancy outcome following (IVF) with ICSI in previous IVF failures. Arch Androl. 2005;51:121–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Cho C, Jung-Ha H, Willis WD, Goulding EH, Stein P, Xu Z, et al. Protamine 2 deficiency leads to sperm DNA damage and embryo death in mice. Biol Reprod. 2003;69:211–7.PubMedCrossRefGoogle Scholar
  14. 14.
    Collins JA, Barnhart KT, Schlegel PN. Do sperm DNA integrity tests predict pregnancy with in vitro fertilization? Fertil Steril. 2008;89:823–31.PubMedCrossRefGoogle Scholar
  15. 15.
    Comizzoli P, Marquant-Le Guienne B, Heyman Y, Renard JP. Onset of the first S-phase is determined by a paternal effect during the G1-phase in bovine zygotes. Biol Reprod. 2000;62:1677–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Ebner T, Moser M, Sommergruber M, Tews G. Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: a review. Hum Reprod Update. 2003;9:251–62.PubMedCrossRefGoogle Scholar
  17. 17.
    Ellington JE, Evenson DP, Wright Jr RW, Jones AE, Schneider CS, Hiss GA, et al. Higher-quality human sperm in a sample selectively attach to oviduct (fallopian tube) epithelial cells in vitro. Fertil Steril. 1999;71:924–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Evenson DP, Darzynkiewicz Z, Melamed MR. Relation of mammalian sperm chromatin heterogeneity to fertility. Science. 1980;210:1131–3.PubMedCrossRefGoogle Scholar
  19. 19.
    Evenson DP, Jost LK, Marshall D, Zinaman MJ, Clegg E, Purvis K, et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod. 1999;14:1039–49.PubMedCrossRefGoogle Scholar
  20. 20.
    Fernandez-Gonzalez R, Moreira PN, Perez-Crespo M, Sanchez-Martin M, Ramirez MA, Pericuesta E, et al. Long-term effects of mouse intracytoplasmic sperm injection with DNA-fragmented sperm on health and behavior of adult offspring. Biol Reprod. 2008;78:761–72.PubMedCrossRefGoogle Scholar
  21. 21.
    Frydman N, Prisant N, Hesters L, Frydman R, Tachdjian G, Cohen-Bacrie P, et al. Adequate ovarian follicular status does not prevent the decrease in pregnancy rates associated with high sperm DNA fragmentation. Fertil Steril. 2008;89:92–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Gandini L, Lombardo F, Paoli D, Caruso F, Eleuteri P, Leter G, et al. Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage. Hum Reprod. 2004;19:1409–17.PubMedCrossRefGoogle Scholar
  23. 23.
    Giwercman A, Lindstedt L, Larsson M, Bungum M, Spano M, Levine RJ, et al. Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study. Int J Androl. 2009.Google Scholar
  24. 24.
    Gu LJ, Chen ZW, Chen ZJ, Xu JF, Li M. Sperm chromatin anomalies have an adverse effect on the outcome of conventional in vitro fertilization: a study with strictly controlled external factors. Fertil Steril. 2009;92:1344–6.PubMedCrossRefGoogle Scholar
  25. 25.
    Hammadeh ME, Al-Hasani S, Stieber M, Rosenbaum P, Kupker D, Diedrich K, et al. The effect of chromatin condensation (aniline blue staining) and morphology (strict criteria) of human spermatozoa on fertilization, cleavage and pregnancy rates in an intracytoplasmic sperm injection programme. Hum Reprod. 1996;11:2468–71.PubMedGoogle Scholar
  26. 26.
    Henkel R, Kierspel E, Hajimohammad M, Stalf T, Hoogendijk C, Mehnert C, et al. DNA fragmentation of spermatozoa and assisted reproduction technology. Reprod Biomed Online. 2003;7:477–84.PubMedCrossRefGoogle Scholar
  27. 27.
    Host E, Lindenberg S, Smidt-Jensen S. The role of DNA strand breaks in human spermatozoa used for IVF and ICSI. Acta Obstet Gynecol Scand. 2000;79:559–63.PubMedCrossRefGoogle Scholar
  28. 28.
    Huszar G, Jakab A, Sakkas D, Ozenci CC, Cayli S, Delpiano E, et al. Fertility testing and ICSI sperm selection by hyaluronic acid binding: clinical and genetic aspects. Reprod Biomed Online. 2007;14:650–63.PubMedCrossRefGoogle Scholar
  29. 29.
    Huszar G, Ozkavukcu S, Jakab A, Celik-Ozenci C, Sati GL, Cayli S. Hyaluronic acid binding ability of human sperm reflects cellular maturity and fertilizing potential: selection of sperm for intracytoplasmic sperm injection. Curr Opin Obstet Gynecol. 2006;18:260–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Lin MH, Kuo-Kuang Lee R, Li SH, Lu CH, Sun FJ, Hwu YM. 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. 2008;90:352–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Liu DY, Baker HW. Human sperm bound to the zona pellucida have normal nuclear chromatin as assessed by acridine orange fluorescence. Hum Reprod. 2007;22:1597–602.PubMedCrossRefGoogle Scholar
  32. 32.
    Meseguer M, Martinez-Conejero JA, O'connor JE, Pellicer A, Remohi J, Garrido N. The significance of sperm DNA oxidation in embryo development and reproductive outcome in an oocyte donation program: a new model to study a male infertility prognostic factor. Fertil Steril. 2008;89:1191–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Metwally M, Cutting R, Tipton A, Skull J, Ledger WL, Li TC. Effect of increased body mass index on oocyte and embryo quality in IVF patients. Reprod Biomed Online. 2007;15:532–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Micinski P, Pawlicki K, Wielgus E, Bochenek M, Tworkowska I. The sperm chromatin structure assay (SCSA) as prognostic factor in IVF/ICSI program. Reprod Biol. 2009;9:65–70.PubMedGoogle Scholar
  35. 35.
    Morris ID, Ilott S, Dixon L, Brison DR. 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. 2002;17:990–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Munne S, Ary J, Zouves C, Escudero T, Barnes F, Cinioglu C, et al. Wide range of chromosome abnormalities in the embryos of young egg donors. Reprod Biomed Online. 2006;12:340–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Muriel L, Meseguer M, Fernandez JL, Alvarez J, Remohi 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. 2006;21:738–44.PubMedCrossRefGoogle Scholar
  38. 38.
    Payne JF, Raburn DJ, Couchman GM, Price TM, Jamison MG, Walmer DK. Redefining the relationship between sperm deoxyribonucleic acid fragmentation as measured by the sperm chromatin structure assay and outcomes of assisted reproductive techniques. Fertil Steril. 2005;84:356–64.PubMedCrossRefGoogle Scholar
  39. 39.
    Perreault SD, Aitken RJ, Baker HW, Evenson DP, Huszar G, Irvine DS, et al. Integrating new tests of sperm genetic integrity into semen analysis: breakout group discussion. Adv Exp Med Biol. 2003;518:253–68.PubMedCrossRefGoogle Scholar
  40. 40.
    Sakkas D. The use of blastocyst culture to avoid inheritance of an abnormal paternal genome after ICSI. Hum Reprod. 1999;14:4–5.PubMedCrossRefGoogle Scholar
  41. 41.
    Sakkas D, D'arcy Y, Percival G, Sinclair L, Afnan M, Sharif K. Use of the egg-share model to investigate the paternal influence on fertilization and embryo development after in vitro fertilization and intracytoplasmic sperm injection. Fertil Steril. 2004;82:74–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Sakkas D, Gardner DK. Noninvasive methods to assess embryo quality. Curr Opin Obstet Gynecol. 2005;17:283–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Sati L, Ovari L, Bennett D, Simon SD, Demir R, Huszar G. Double probing of human spermatozoa for persistent histones, surplus cytoplasm, apoptosis and DNA fragmentation. Reprod Biomed Online. 2008;16:570–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D. Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril. 2004;82:378–83.PubMedCrossRefGoogle Scholar
  45. 45.
    Shoukir Y, Chardonnens D, Campana A, Sakkas D. Blastocyst development from supernumerary embryos after intracytoplasmic sperm injection: a paternal influence? Hum Reprod. 1998;13:1632–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Spano M, Bonde JP, Hjollund HI, Kolstad HA, Cordelli E, Leter G. Sperm chromatin damage impairs human fertility. The Danish First Pregnancy Planner Study Team. Fertil Steril. 2000;73:43–50.PubMedCrossRefGoogle Scholar
  47. 47.
    Tarozzi N, Nadalini M, Stronati A, Bizzaro D, Dal Prato L, Coticchio G, et al. Anomalies in sperm chromatin packaging: implications for assisted reproduction techniques. Reprod Biomed Online. 2009;18:486–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Taylor DM, Ray PF, Ao A, Winston RM, Handyside AH. Paternal transcripts for glucose-6-phosphate dehydrogenase and adenosine deaminase are first detectable in the human preimplantation embryo at the three- to four-cell stage. Mol Reprod Dev. 1997;48:442–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Tesarik J, Greco E, Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Hum Reprod. 2004;19:611–5.PubMedCrossRefGoogle Scholar
  50. 50.
    Tomsu M, Sharma V, Miller D. Embryo quality and IVF treatment outcomes may correlate with different sperm comet assay parameters. Hum Reprod. 2002;17:1856–62.PubMedCrossRefGoogle Scholar
  51. 51.
    Valbuena D, Martin J, De Pablo JL, Remohi J, Pellicer A, Simon C. Increasing levels of estradiol are deleterious to embryonic implantation because they directly affect the embryo. Fertil Steril. 2001;76:962–8.PubMedCrossRefGoogle Scholar
  52. 52.
    Velez De La Calle JF, Muller A, Walschaerts M, Clavere JL, Jimenez C, Wittemer C, et al. 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. 2008;90:1792–9.PubMedCrossRefGoogle Scholar
  53. 53.
    Ward F, Rizos D, Corridan D, Quinn K, Boland M, Lonergan P. Paternal influence on the time of first embryonic cleavage post insemination and the implications for subsequent bovine embryo development in vitro and fertility in vivo. Mol Reprod Dev. 2001;60:47–55.PubMedCrossRefGoogle Scholar
  54. 54.
    Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008;23:2663–8.PubMedCrossRefGoogle Scholar
  55. 55.
    Zini A, Meriano J, Kader K, Jarvi K, Laskin CA, Cadesky K. Potential adverse effect of sperm DNA damage on embryo quality after ICSI. Hum Reprod. 2005;20:3476–80.PubMedCrossRefGoogle Scholar
  56. 56.
    Zini A, Sigman M. Are tests of sperm DNA damage clinically useful? Pros and cons. J Androl. 2009;30:219–29.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Armand Zini
    • 1
    • 5
  • Wael Jamal
    • 2
    • 3
  • Lisa Cowan
    • 4
  • Naif Al-Hathal
    • 1
  1. 1.Division of Urology, Department of SurgeryMcGill UniversityMontrealCanada
  2. 2.Department of Obstetrics and GynecologyUniversity of MontrealMontrealCanada
  3. 3.OVO Fertility ClinicMontrealCanada
  4. 4.The Victoria Fertility CentreVictoriaCanada
  5. 5.St. Mary’s HospitalMontrealCanada

Personalised recommendations