Controversies Surrounding the 2010 World Health Organization Cutoff Values for Human Semen Characteristics and Its Impact on Unexplained Infertility

Chapter

Abstract

In 2010, the World Health Organization (WHO) published new reference criteria for human semen characteristics. Important methodological issues, including patient selection and methods for semen assessments, elucidate why reference values are markedly lower than those earlier reported. The validity of the new criteria as a representation of the semen quality of fertile men has been questioned as they have been generated from a small group of recent fathers of restricted geographic regions. The 2010 WHO criteria are likely to have a significant clinical effect as more men will be classified as having unexplained male infertility. This may lead to a deferment of referral and could delay the definitive diagnosis and management of the infertile couple. Due to the several inherent limitations of semen analysis as a surrogate marker of male infertility, physicians should exercise caution when interpreting results. Semen analysis alone is usually insufficient for the diagnosis, as it does not account for sperm dysfunction, such as immature chromatin, oxidative stress (OS), and DNA damage. A male infertility evaluation must go far beyond a simple semen analysis, as it has to be complemented with a proper physical examination, a comprehensive history taking, and relevant endocrine, genetic, and other investigations.

Keywords

Unexplained male infertility Semen analysis Andrology Diagnosis Treatment Spermatozoa World Health Organization Laboratory manuals Reference values 

References

  1. 1.
    World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 2nd ed. Cambridge: Cambridge University Press; 1987. p. 80.Google Scholar
  2. 2.
    World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 3rd ed. Cambridge: Cambridge University Press; 1992. p. 107.Google Scholar
  3. 3.
    World Health Organization. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 4th ed. Cambridge: Cambridge University Press; 1999. p. 128.Google Scholar
  4. 4.
    World Health Organization. WHO laboratory manual for the examination and processing of human semen, 5th ed. Geneva: World Health Organization; 2010. p. 271.Google Scholar
  5. 5.
    Christopher LR, Barratt CLR, Mansell S, Beaton C, Tardif S, Oxenham SK. Diagnostic tools in male infertility—the question of sperm dysfunction. Asian J Androl. 2011;13:53–8.CrossRefGoogle Scholar
  6. 6.
    Esteves SC, Zini A, Aziz N, Alvarez JG, Sabanegh ES Jr, Agarwal A. Critical appraisal of World Health Organization’s new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology. 2012;79(1):16–22.PubMedCrossRefGoogle Scholar
  7. 7.
    Haidl G. New WHO-reference limits-revolution or storm in a teapot? Asian J Androl. 2011;13(2):208–11.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Murray KS, James A, McGeady JB, Reed ML, Kuang WW, Nangia AK. The effect of the new 2010 World Health Organization criteria for semen analyses on male infertility. Fertil Steril. 2012;98(6):1428–31.PubMedCrossRefGoogle Scholar
  9. 9.
    Yerram N, Sandlow JI, Brannigan RE. Clinical implications of the new 2010 WHO reference ranges for human semen characteristics. J Androl. 2012;33(3):289–90.PubMedCrossRefGoogle Scholar
  10. 10.
    Esteves SC, Hamada A, Kondray V, Pitchika A, Agarwal A. What every gynecologist should know about male infertility: an update. Arch Gynecol Obstet. 2012;286(1):217–29.PubMedCrossRefGoogle Scholar
  11. 11.
    Esteves SC, Miyaoka R, Agarwal A. An update on the clinical assessment of the infertile male. [corrected]. Clinics (Sao Paulo). 2011;66:691–700. (Erratum in: Clinics (Sao Paulo). 2012;67:203).CrossRefGoogle Scholar
  12. 12.
    Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C, Carson SA, Cisneros P, Steinkampf MP, Hill JA, Xu D, Vogel DL, National Cooperative Reproductive Medicine Network. Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2001;345(19):1388–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Moghissi KS, Wallach EE. Unexplained infertility. Fertil Steril 1983; 39: 5–21.PubMedGoogle Scholar
  14. 14.
    van der Steeg JW, Steures P, Eijkemans MJ, F Habbema JD, Hompes PG, Kremer JA, et al. Role of semen analysis in subfertile couples. Fertil Steril. 2011;95:1013–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Álvarez C, Castilla JA, Martínez L, Ramírez JP, Vergara F, Gaforio JJ. Biological variation of seminal parameters in healthy subjects. Hum Reprod. 2003;18(10):2082–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Castilla JA, Alvarez C, Aguilar J, González-Varea C, Gonzalvo MC, Martínez L. Influence of analytical and biological variation on the clinical interpretation of seminal parameters. Hum Reprod. 2006;21(4):847–51.PubMedCrossRefGoogle Scholar
  17. 17.
    Keel BA. Within- and between-subject variation in semen parameters in infertile men and normal semen donors. Fertil Steril. 2006;85(1):128–34.PubMedCrossRefGoogle Scholar
  18. 18.
    Poland ML, Moghissi KS, Giblin PT, Ager JW, Olson JM. Variation of semen measures within normal men. Fertil Steril. 1985;44(3):396–400.PubMedGoogle Scholar
  19. 19.
    Jequier AM. Is quality assurance in semen analysis still really necessary? A clinician’s viewpoint. Hum Reprod. 2005;20:2039–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Baker HW, Kovacs GT. Spontaneous improvement in semen quality: regression towards the mean. Int J Androl. 1985;8(6):421–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Berman NG, Wang C, Paulsen CA. Methodological issues in the analysis of human sperm concentration data. J Androl. 1996;17(1):68–73.PubMedGoogle Scholar
  22. 22.
    Carlsen E, Petersen JH, Andersson AM, Skakkebaek NE. Effects of ejaculatory frequency and season on variations in semen quality. Fertil Steril. 2004;82(2):358–66.PubMedCrossRefGoogle Scholar
  23. 23.
    Sánchez-Pozo MC, Mendiola J, Serrano M, Mozas J, Björndahl L, Menkveld R, Lewis SEM, Mortimer D, Jørgensen N, Barratt CLR, Fernández MF, Castilla JA. Proposal of guidelines for the appraisal of SEMen QUAlity studies (SEMQUA). Hum Reprod. 2013;28(1):10–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Hamada A, Esteves SC, Nizza M, Agarwal A. Unexplained male infertility: diagnosis and management. Int Braz J Urol. 2012;38:576–94.PubMedCrossRefGoogle Scholar
  25. 25.
    Samplaski MK, Agarwal A, Sharma R, Sabanegh E. New generation of diagnostic tests for infertility: review of specialized semen tests. Int J Urol. 2010;17:839–47.PubMedCrossRefGoogle Scholar
  26. 26.
    Kovac JR, Pastuszak AW, Lamb DJ. The use of genomics, proteomics, and metabolomics in identifying biomarkers of male infertility. Fertil Steril. 2013;99:998–1007.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Sullivan EA, Zegers-Hochschild F, Mansour R, Ishihara O, de Mouzon J, Nygren KG, Adamson GD. International Committee for Monitoring Assisted Reproductive Technologies (ICMART) world report: assisted reproductive technology 2004. Hum Reprod. 2013;28:1375–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol. 2008;59(1):2–11.PubMedCrossRefGoogle Scholar
  29. 29.
    Esteves SC, Agarwal A. Novel concepts in male infertility. Int Braz J Urol. 2011;37(1):5–15.PubMedCrossRefGoogle Scholar
  30. 30.
    Ashwood-Smith MJ, Edwards RG. DNA repair by oocytes. Mol Hum Reprod. 1996;2:46–51.PubMedCrossRefGoogle Scholar
  31. 31.
    Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril. 1997;68(3):519–24.PubMedCrossRefGoogle Scholar
  32. 32.
    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(1):43–50.PubMedCrossRefGoogle Scholar
  33. 33.
    Zini A, Bielecki R, Phang D, Zenzes MT. Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men. Fertil Steril. 2001;75(4):674–77.PubMedCrossRefGoogle Scholar
  34. 34.
    Agarwal A, Sigman M. Is sperm DNA integrity assessment useful? Opposing views. J Urol. 2013;90:1645–7.CrossRefGoogle Scholar
  35. 35.
    Zini A, Sigman M. Are tests of sperm DNA damage clinically use.ful? Pros and cons. J Androl. 2009;30(3):219–29.PubMedCrossRefGoogle Scholar
  36. 36.
    Snow-Lisy D, Sabanegh E Jr. What does the clinician need from an andrology laboratory? Front Biosci (Elite Ed). 2013;5:289–304.Google Scholar
  37. 37.
    Keel BA, Sternbridge TW, Pineda G, Serafy NT. Lack of standardisation in performance of the semen analysis among laboratories in the United States. Fertil Steril. 2002;78:603–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Riddell D, Pacey A, Whittington K. Lack of compliance in UK andrology laboratories to World Health Organisation recommendations for sperm morphology assessment. Hum Reprod. 2005;20:3441–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Alvarez C, Castilla JA, Ramírez JP, et al. External quality control program for semen analysis: Spanish experience. J Assist Reprod Genet. 2005;22:379–87.PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Cooper TG, Björndahl L, Vreeburg J, et al. Semen analysis and external quality control schemes for semen analysis need global standardization. Int J Androl. 2002;25:(3)6–11.Google Scholar
  41. 41.
    Esteves SC, Agarwal A. Ensuring that reproductive laboratories provide high-quality services. In: Bento FC, Esteves SC, Agarwal A. Quality management in ART clinics: a practical guide, 1st ed. New York: Springer US 2013;129–46.CrossRefGoogle Scholar
  42. 42.
    Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16:231–245.PubMedCrossRefGoogle Scholar
  43. 43.
    Stewart TM, Liu DY, Garrett C, Jørgensen N, Brown EH, Baker HW. Associations between andrological measures, hormones and semen quality in fertile Australian men: inverse relationship between obesity and sperm output. Hum Reprod. 2009;24(7):1561–8.PubMedCrossRefGoogle Scholar
  44. 44.
    Slama R, Eustache F, Ducot B, Jensen TK, Jørgensen N, Horte A, et al. Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities. Hum Reprod. 2002;17(2):503–15.PubMedCrossRefGoogle Scholar
  45. 45.
    Swan SH, Brazil C, Drobnis EZ, Liu F, Kruse RL, Hatch M, Redmon JB, Wang C, Overstreet JW, Study for Future Families Research Group. Geographic differences in semen quality of fertile U.S. males. Environ Health Perspect. 2003;111(4):414–20.PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Jensen TK, Slama R, Ducot B, Suominen J, Cawood EH, Andersen AG, et al. Regional differences in waiting time to pregnancy among fertile couples from four European cities. Hum Reprod. 2001;16(12):2697–704.PubMedCrossRefGoogle Scholar
  47. 47.
    Haugen TB, Egeland T, Magnus O. Semen parameters in Norwegian fertile men. J Androl. 2006:27:66–71.PubMedCrossRefGoogle Scholar
  48. 48.
    Auger J, Eustache F, Andersen AG, Irvine DS, Jørgensen N, Skakkebaek NE. Sperm morphological defects related to environment, lifestyle and medical history of 1001 male partners of pregnant women from four European cities. Hum Reprod. 2001;16(12):2710–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Handelsman DJ. Estrogens and falling sperm counts. Reprod Fertil Dev. 2001;13:317–24.PubMedCrossRefGoogle Scholar
  50. 50.
    Sadeu JC, Hughes CL, Agarwal S, Foster WG. Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications. Crit Rev Toxicol. 2010;40(7):633–52.PubMedCrossRefGoogle Scholar
  51. 51.
    Carlsen E, Giwercman A, Keiding N, et al. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992;305:609–13.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    American Urological Association. Best practice statement on the optimal evaluation of the infertile male (revised 2010). http://www.auanet.org/content/media/optimalevaluation2010.pdf. Accessed 5 Oct 2013.
  53. 53.
    Dohle GR, Diemer T, Giwercman A, et al. Chapter 2: Investigations. In: Dohle GR, Diemer T, Giwercman A, et al. Guidelines on male infertility. European Association of Urology. 2010. http://www.uroweb.org/gls/pdf/Male%20Infertility%202010.pdf. Accessed 5 Oct 2013.
  54. 54.
    The Male Infertility Best Practice Policy Committee of the American Urological Association. Practice Committee of the American Society for Reproductive Medicine. Report on varicocele and infertility. Fertil Steril. 2004;82:S142–5.Google Scholar
  55. 55.
    Dohle GR, Diemer T, Giwercman A, et al. Chapter 6: Varicocele. In: Dohle GR, Diemer T, Giwercman A, et al. (eds). Guidelines on male infertility. European Association of Urology; 2010. http://www.uroweb.org/gls/pdf/Male%20Infertility%202010.pdf. Accessed 5 Oct 2013.
  56. 56.
    Sociedade Brasileira de Urologia & Colégio Brasileiro de Radiologia; Projeto Diretrizes da Associação Médica Brasileira: Varicocele. http://www.projetodiretrizes.org.br/8_volume/40-Varicocele.pdf. Accessed: 5 Oct 2013.
  57. 57.
    Practice Committee of the American Society for Reproductive Medicine: Report on varicocele and infertility: a committee opinion. Fertil Steril. 2014;102:1556-60.Google Scholar
  58. 58.
    Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S, et al. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril. 1988;49:112–7.PubMedGoogle Scholar
  59. 59.
    Coetzee K, Kruge TF, Lombard CJ. Predictive value of normal sperm morphology: a structured literature review. Hum Reprod Update. 1998;4:73–82.PubMedCrossRefGoogle Scholar
  60. 60.
    Van Waart J, Kruger TF, Lombard CJ, Ombelet W. Predictive value of normal sperm morphology in intrauterine insemination (IUI): a structured literature review. Hum Reprod Update. 2001;7:495–500.PubMedCrossRefGoogle Scholar
  61. 61.
    World Health Organization. WHO laboratory manual for the examination and processing of human semen, 5th ed. Geneva: World Health Organization; 2010. Appendix 6, p. 252.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2015

Authors and Affiliations

  1. 1.ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male ReproductionSão PauloBrazil

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