Skip to main content
Log in

Evaluating a novel panel of sperm function tests for utility in predicting intracytoplasmic sperm injection (ICSI) outcome

  • Technological Innovations
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The objective of this study was to evaluate a panel of three sperm function tests; tests known to assess different aspects of sperm functionality and genomic integrity, the: 1) Sperm DNA Accelerated Decondensation (SDADTM) Test, 2) Sperm DNA Decondensation (SDDTM) Test, and 3) Sperm Penetration Assay (SPA), determining if positive and negative test scores correlated with failed and successful ICSI outcomes, respectfully.

Methods

A prospective, double blinded, cohort study was performed. One study sample (ejaculated semen) was collected by each of the 60 male partners of the 60 couples enrolled in the study; males whose female partners were found to have no major female factor issues. The sperm from each male was analyzed in the SPA, and SDAD and SDD Tests, and used for ICSI (1 ICSI cycle per couple).

Results

The ICSI cycle pregnancy rate for this study was 50 %, with a delivery rate = 40 % (n = 60 ICSI cycles). The SPA and SDD Test scores did not significantly predict ICSI outcome when used as stand-alone tests (p> > 0.05). However, when the SPA and SDD Test scores were used together, ICSI outcomes for a subgroup of 10 (16.7 %) males, were significantly predicted (p = 0.03), with 1 live birth, and 9 negatives where the transferred embryos did not implant. In total, 38.4 % of the couples in this study were found to have a very poor chance for a successful ICSI cycle.

Conclusion

SDAD Test scores alone, and SPA and SDD Test scores used together, significantly predicted failed ICSI outcomes. This indicates that the scores obtained when analyzing patients’ sperm using a panel of sperm function tests; specifically, the SPA, and SDAD and SDD Tests, can be used to identify infertile couples who should not be directed to ICSI.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update. 2003;9:331–45.

    Article  PubMed  CAS  Google Scholar 

  2. Agarwal A. Current and future perspectives on intracytoplasmic sperm injection: a critical commentary. Reprod BioMed Online. 2007a;15:719–27.

    Article  Google Scholar 

  3. Agarwal A, Prabakaran S. Clinical relevance of oxidative stress in patients with male factor infertility; evidence-based analysis. Am Urol Assoc Updat Ser. 2007b;26:1–11.

    Google Scholar 

  4. 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;89:124–8.

    Article  PubMed  Google Scholar 

  5. Aitken RL, Buckingham D, West K, Wu FC, Zikopoulos K, Richardson DW. Differential contribution of leucocytes and spermatozoa to the high levels of reactive oxygen species recorded in the ejaculates of oligozoospermic patients. J Reprod Fertil. 1992;94:451–462.

    Google Scholar 

  6. Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, et al. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod. 1998;59:1037–46.

    Article  PubMed  CAS  Google Scholar 

  7. Aitken RJ. Whither must spermatozoa wander? The future of laboratory seminology. Asian J Androl. 2010;12:99–103.

    Article  PubMed  Google Scholar 

  8. Anderson AN, Goossens V, Ferraretti AP, et al. Assisted reproductive technology in Europe. Hum Reprod. 2008;23:1158–76.

    Article  Google Scholar 

  9. Bar-Charma N, Lamb DJ. Evaluation of sperm function. What is available in the modern andrology laboratory. Urol Clin N Am. 1994;21:433–46.

    Google Scholar 

  10. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care. Hum Reprod. 2007;22:1506–12.

    Article  PubMed  Google Scholar 

  11. Bonde JPE, Ernst E, Jensen TK, et al. Relation between semen quality and fertility: a population-based study of 430 first-pregnancy planners. Lancet. 1998;352:1172–7.

    Article  PubMed  CAS  Google Scholar 

  12. Brown DB, Blake E, Wolgemuth D, Gordon K, Ruddle F. Chromatin decondensation and DNA synthesis in human sperm activated in vitro by using Xenopus laevis egg extracts. J Exp Zool. 1987;242:215–31.

    Article  PubMed  CAS  Google Scholar 

  13. Brown DB, Nagamani M. Use of Xenopus laevis frog egg extract in diagnosing human male unexplained infertility. Yale J Biol Med. 1992;65:29–38.

    PubMed  CAS  Google Scholar 

  14. Brown DB, Hayes EJ, Uchida T, Nagamani M. Some cases of human male infertility are explained by abnormal in vitro human sperm activation. Fertil Steril. 1995;64:612–22.

    PubMed  CAS  Google Scholar 

  15. Brown DB, Gelman KM, Whitman-Elia GF, Witt MA, Kordus RJ, Roseff SJ. Comparing the sperm decondensation (SDDTM) and sperm DNA accelerated decondensation (SDADTM) tests’ capacity for identifying infertile males likely to benefit from anti-oxidant treatment. Fertil Steril. 2010;94 Suppl 4:S238.

    Article  Google Scholar 

  16. Bungum M, Spano M, Humaidan P, Eleuteri P, Rescia M, Giwercman A. Sperm chromatin structure assay parameters measured after density gradient centrifugation are not predictive for the outcome of ART. Hum Reprod. 2008;23:4–10.

    Article  PubMed  CAS  Google Scholar 

  17. Bungum M (2012) Sperm DNA integrity assessment: a new tool in diagnosis and treatment of fertility. Obstet Gynecol Int doi:10.1155/2012/531042.

  18. Cohen J, Edwards RG, Fehilly CB, Fishel SB, Hewitt J, Rowland G, et al. Treatment of male infertility by in vitro fertilization: factors affecting fertilizations and pregnancy. Acta Eur Fertil. 1984;15:455–65.

    PubMed  CAS  Google Scholar 

  19. Davies MJ, Moore VM, Willson KJ, Van Essen P, Priest K, Scott H, et al. Reproductive technologies and the risk of birth defects. N Engl J Med. 2012;366:1803–13.

    Article  PubMed  CAS  Google Scholar 

  20. Dunson DB, Baird DD, Colombo B. Increased infertility with age in men and women. Obstet Gynecol. 2004;103:51–6.

    Article  PubMed  Google Scholar 

  21. Evenson DP, Darzynkiewicz Z, Melamed MR. Relation of mammalian sperm chromatin heterogeneity to fertility. Science. 1980;210:1131–3.

    Article  PubMed  CAS  Google Scholar 

  22. Evenson DP, Jost LK, Marshall D, 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.

    Article  PubMed  CAS  Google Scholar 

  23. Gandlnl L, Lombardo F, Paoli D, et al. Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage. Hum Reprod. 2004;19:1409–17.

    Article  Google Scholar 

  24. Gomez E, Irvine DS, Aitken RJ. Evaluation of a spectrophotometric assay for the measurement of malondialdehyde and 4-hydroxyalkenals in human spermatozoa: relationships with semen quality and sperm function. Int J Androl. 1998;21:81–94.

    Article  PubMed  CAS  Google Scholar 

  25. Greco E., Lacobelli M, Ferrero S, Baroni E, Minasi MG, Ubaldi F, et al. ICSI in cases of sperm DNA damage: beneficial effect of oral anti-oxidant treatment. J Androl. 2005;20:2590–2594.

    Google Scholar 

  26. Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, et al. Sperm morphology, motility and concentration in infertile and fertile men. N Engl J Med. 2001;345:1388–93.

    Article  PubMed  CAS  Google Scholar 

  27. Johnson AR, Bassham B, Lipshultz LI, Lamb DJ. Methodology for the optimized sperm penetration assay. In: Keel B, Webster B, editors. Handbook of the laboratory diagnosis and treatment of infertility. Boca Raton: CRC Press; 1990. p. 135–47.

    Google Scholar 

  28. Johnson A, Bassham B, Lipshultz LI, Lamb DJ. A quality control system for the optimized sperm penetration assay. Fertil Steril. 1995;64:832–7.

    PubMed  CAS  Google Scholar 

  29. Kemal Duru N, Morshedi M, Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril. 2000;74:287–91.

    Article  Google Scholar 

  30. Lamb DJ. Semen analysis in 21st century medicine: the need for sperm function testing. Asian J Androl. 2010;12:64–70.

    Article  PubMed  Google Scholar 

  31. Larson KL, DeJonge CJ, Barnes AM, Jost LK, Evenson DP. Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. Hum Reprod. 2000;15:1717–22.

    Article  PubMed  CAS  Google Scholar 

  32. Larson-Cook KL, Brannian JD, Hansen KA, Kasperson KM, Aamold ET, Evenson DP. Relationship between the outcomes of assisted reproductive techniques and sperm DNA fragmentation as measured by the sperm chromatin structure assay. Fertil Steril. 2003;80:895–902.

    Article  PubMed  Google Scholar 

  33. Longo FJ, Kunkle M. Transformation of sperm nuclei upon insemination. Curr Top Dev Biol. 1978;12:149–84.

    Article  PubMed  CAS  Google Scholar 

  34. Matsumoto K, Nagata K, Miyaji-Yamaguchi M, Kikuchi A, Tsujimoto M. Sperm chromatin decondensation by template activating factor I through direct interaction with basic proteins. Mol Cell Biol. 1999;19:6940–52.

    PubMed  CAS  Google Scholar 

  35. Merryman DC, Stringfellow SE, Yancey CA, Houserman VL, Long CA, Honea KL. Does in vitro fertilization (IVF) with intracytoplasmic sperm injection compensate for impaired sperm function as predicted by the sperm penetration assay (SPA)? Fert Steril. 2001;76 Suppl 1:S215.

    Article  Google Scholar 

  36. Merryman DC, Stringfellow SE, Dalton KE, Houserman VL, Long CA, Honea KL. Sperm capacitation index (SCI) predicts pregnancy outcome with controlled ovarian hyperstimulation (COH) + intrauterine insemination (IUI). Fertil Steril. 2007;88 Suppl 1:S118–9.

    Google Scholar 

  37. Merryman DC, Rivnay B, Honea KL, Brown DB. Sperm DNA decondensation and sperm penetration assay with gradient preparation are not predictive of pregnancy outcome in in vitro fertilization cycles with intracytoplasmic sperm injection. Fertil Steril. 2007;88 Suppl 1:S380–1.

    Article  Google Scholar 

  38. Misro MM, Choudbury L, Upreti K, Gautam D, Chaki SP, Mahaian AS, et al. Use of hydrogen peroxide to assess the sperm susceptibility to oxidative stress in subjects presenting a normal semen profile. Int J Androl. 2004;27:82–7.

    Article  PubMed  CAS  Google Scholar 

  39. Muratori M, Marchiani S, et al. Markers of human sperm functions in the ICSI era. Front Biosci. 2011;16:1344–63.

    Article  PubMed  CAS  Google Scholar 

  40. Natali A, Turek PJ. An assessment of new sperm tests for male infertility. Urology. 2011;77:1027–34.

    Article  PubMed  Google Scholar 

  41. Ochsendorft FR. Infections in the male genital tract and reactive oxygen species. Hum Reprod. 1999;5:399–420.

    Article  Google Scholar 

  42. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340:17–8.

    Article  PubMed  CAS  Google Scholar 

  43. Payne JF, Raburn DJ, Couchman GM, Price TM, Jamison MG, Walmer DK. Redefining the relationship between sperm deoxyribonucleic acid fragmentations as measured by the sperm chromatin structure assay and outcomes of assisted reproductive tehniques. Fertil Steril. 2005;84:356–64.

    Article  PubMed  Google Scholar 

  44. Philpott A, Leno GH, Laskey RA. Sperm decondensation in Xenopus egg cytoplasm is mediated by nucleoplasmin. Cell. 1991;65:569–78.

    Article  PubMed  CAS  Google Scholar 

  45. Philpott A, Leno GH. Nucleoplasmin remodels sperm chromatin in Xenopus egg extracts. Cell. 1992;69:759–67.

    Article  PubMed  CAS  Google Scholar 

  46. Rogers BJ, Van Campen H, Ueno M, Lambert H, Bronson R, Hanson RW. Analysis of human spermatozoa fertilizing ability using zona-free ova. Fertil Steril. 1979;32:664–70.

    PubMed  CAS  Google Scholar 

  47. Sawyer DE, Brown DB. Diminished decondensation and DNA synthesis in activated sperm from rats treated with cyclophosphamide. Toxicol Lett. 2000;114:19–26.

    Article  PubMed  CAS  Google Scholar 

  48. Sawyer DE, Brown DB. The use of a in vivo sperm activation assay to detect chemically-induced damage of human sperm nuclei. Reprod Toxicol. 1995;9:351–7.

    Article  PubMed  CAS  Google Scholar 

  49. Sawyer DE, Hillman GR, Uchida T, Brown DB. Altered nuclar activation parametersof Rat sperm treated in vitro with chromatin damaging agents. Toxicol Sci. 1998;44:52–62.

    PubMed  CAS  Google Scholar 

  50. Sigman M. Medications that impair male fertility. Sex Reprod Menopause. 2007;5:11–6.

    Google Scholar 

  51. Sigman M, Zini A. Semen analysis and sperm function assays: what do they mean? Semin Reprod Med. 2009;27:115–23.

    Article  PubMed  Google Scholar 

  52. Tirado EE, Sharma R, Sawyer DE, Awasthi YC, Brown DB. Effects of oxidative stress on human sperm activation. Fertil Steril. 2003;80 Suppl 3:S240.

    Article  Google Scholar 

  53. Turkyilmaz Z, Gulen S, Sonmez K, Karabulut R, Dincer S, Can Basaklar A, et al. Increased nitric oxide is accompanied by lipid oxidation in adolescent varicocele. Int J Androl. 2004;27:183–7.

    Article  PubMed  Google Scholar 

  54. World Health Organization. Towards more objectivity in diagnosis and management of male infertility. Int J Androl. 1987;7:1–53.

    Google Scholar 

  55. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press; 2010.

    Google Scholar 

  56. Yanagimachi R, Yanagimachi H, Rogers BJ. The use of zona-free animal ova as a test system for the assessment of the fertilizing capacity of human spermatozoa. Biol Reprod. 1976;15:471–6.

    Article  PubMed  CAS  Google Scholar 

  57. Yanagimachi R. Mechanisms of fertilization in mammals. In: Mastrioni, Biggers J, editors. Fertilization and embryonic development. New York: Plenum Press; 1981. p. 81–187.

    Chapter  Google Scholar 

  58. Yanagimachi R. Problems of sperm fertility: A reproductive biologist’s view. Systems Boil Reprod Med doi:10.3109/19396368.2010.507860.

  59. The Practice Committee of the American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing: a guideline. Fertil Steril. 2013;99:673–677.

    Google Scholar 

  60. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors wish to acknowledge Olivera Vragovic, MBA (Research Manager, Dept. of Ob/Gyn, Boston University School of Medicine), for her invaluable help with the statistical analyses performed during the course of this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David B. Brown.

Additional information

Capsule

A Panel of physiologically relevant sperm function tests was shown to have significant clinical utility when used to predict ICSI outcome.

David B. Brown and Deborah C. Merryman contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brown, D.B., Merryman, D.C., Rivnay, B. et al. Evaluating a novel panel of sperm function tests for utility in predicting intracytoplasmic sperm injection (ICSI) outcome. J Assist Reprod Genet 30, 461–477 (2013). https://doi.org/10.1007/s10815-013-9960-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-013-9960-x

Keywords

Navigation