International Urology and Nephrology

, Volume 47, Issue 9, pp 1441–1456 | Cite as

A systematic review of recent clinical practice guidelines and best practice statements for the evaluation of the infertile male

  • Sandro C. EstevesEmail author
  • Peter Chan
Urology - Review



We systematically identified and reviewed the methods and consistency of recommendations of recently developed clinical practice guidelines (CPG) and best practice statements (BPS) on the evaluation of the infertile male.


MEDLINE and related engines as well as guidelines’ Web sites were searched for CPG and BPS written in English on the general evaluation of male infertility published between January 2008 and April 2015.


Four guidelines were identified, all of which reported to have been recently updated. Systematic review was not consistently used in the BPS despite being reported in the CPG. Only one of them reported having a patient representative in its development team. The CPG issued by the European Association of Urology (EAU) graded some recommendations and related that to levels (but not quality) of evidence. Overall, the BPS issued respectively by the American Urological Association and American Society for Reproductive Medicine concurred with each other, but both differed from the EAU guidelines with regard to methods of collection, extraction and interpretation of data. None of the guidelines incorporated health economics. Important specific limitations of conventional semen analysis results were ignored by all guidelines. Besides variation in the methodological quality, implementation strategies were not reported in two out of four guidelines.


While the various panels of experts who contributed to the development of the CPG and BPS reviewed should be commended on their tremendous efforts aiming to establish a clinical standard in both the evaluation and management of male infertility, we recognized inconsistencies in the methodology of their synthesis and in the contents of their final recommendations. These discrepancies pose a barrier in the general implementation of these guidelines and may limit their utility in standardizing clinical practice or improving health-related outcomes. Continuous efforts are needed to generate high-quality evidence to allow further development of these important guidelines for the evaluation and management of males suffering from infertility.


Clinical practice guidelines Diagnosis Male infertility Standards Systematic review 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    World Health Organization (2000) WHO manual for the standardised investigation and diagnosis of the infertile male. Cambridge University Press, Cambridge. Accessed 4 April 2015
  2. 2.
    US Census Bureau (2011) Population estimates. US Census Bureau, Methodology and Standards Council. Accessed 31 July 2014
  3. 3.
    Right (2014) Statistics by country for infertility. Health Grades Inc. Accessed 17 July 2014
  4. 4.
    Vital and Health Statistics (2006) Center for Disease Control (CDC) Series 23, number 26. Accessed 31 July 2014
  5. 5.
    Practice Committee of the American Society for Reproductive Medicine (2008) Definitions of infertility and recurrent pregnancy loss [Committee opinion]. Fertil Steril 90:S60Google Scholar
  6. 6.
    Dorland WAN (2007) Dorland’s illustrated medical dictionary, 31st edn. Elsevier, New York, p 53Google Scholar
  7. 7.
    Esteves SC, Miyaoka R, Agarwal A (2011) An update on the clinical assessment of the infertile male [corrected]. Clinics (Sao Paulo) 66:691–700CrossRefGoogle Scholar
  8. 8.
    Hamada A, Esteves SC, Nizza M, Agarwal A (2012) Unexplained male infertility: diagnosis and management. Int Braz J Urol 38:576–594CrossRefPubMedGoogle Scholar
  9. 9.
    American Urological Association Education and Research, Inc. (2010) The optimal evaluation of the infertile male: AUA best practice statement. Linthicum (MD): American Urological Association Education and Research, Inc. Accessed 31 July 2014
  10. 10.
    Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6(7):e1000097PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Jungwirth A, Diemer T, Dohle GR, Giwercman A, Kopa Z, Tournaye H, Krausz C (2013) Guidelines on male infertility. European Association of Urology (EAU), Arnhem (The Netherlands), 362 references. Accessed 31 July 2014
  12. 12.
    American Urological Association Education and Research, Inc. (2011) The optimal evaluation of the infertile male: best practice statement reviewed and validity confirmed. Accessed 29 May 2015
  13. 13.
    Practice Committee of American Society for Reproductive Medicine (2015) Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril 103: e18–e25 Accessed 28 May 2015
  14. 14.
    National Collaborating Centre for Women’s and Children’s Health (2013) Fertility: assessment and treatment for people with fertility problems. National Institute for Health and Clinical Excellence (NICE), London (UK), 63 p (Clinical guideline; no. 156). Accessed 28 May 2015
  15. 15.
    Institute of Medicine (2011) In: Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E (eds) Clinical practice guidelines we can trust. National Academies Press, Washington (DC) 2p. Accessed 4 April 2015
  16. 16.
    World Health Organization (2010) WHO laboratory manual for the examination and processing of human semen, 5th edn. WHO press, Geneva. Accessed 4 April 2015
  17. 17.
    Jarow JP, Sharlip ID, Belker AM, Lipshultz LI, Sigman M, Thomas AJ, Schlegel PN, Howards SS, Nehra A, Damewood MD, Overstreet JW, Sadovsky R (2002) Male infertility best practice policy committee of the American Urological Association Inc., best practice policies for male infertility. J Urol 167:2138–2144CrossRefPubMedGoogle Scholar
  18. 18.
    World Health Organization (1999) WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction, 4th edn. Cambridge University Press, Cambridge. Accessed 31 July 2014
  19. 19.
    Esteves SC, Zini A, Aziz N, Alvarez JG, Sabanegh ES Jr, Agarwal A (2012) Critical appraisal of World Health Organization’s new reference values for human semen characteristics and effect on diagnosis and treatment of subfertile men. Urology 79:16–22CrossRefPubMedGoogle Scholar
  20. 20.
    Esteves SC (2014) Clinical relevance of routine semen analysis and controversies surrounding the 2010 World Health Organization criteria for semen examination. Int Braz J Urol 40:443–453CrossRefPubMedGoogle Scholar
  21. 21.
    Murray KS, James A, McGeady JB, Reed ML, Kuang WW, Nangia AK (2012) The effect of the new 2010 World Health Organization criteria for semen analyses on male infertility. Fertil Steril 98:1428–1431CrossRefPubMedGoogle Scholar
  22. 22.
    Guzick DS, Overstreet JW, Factor-Litvak P, Brazil CK, Nakajima ST, Coutifaris C et al (2001) Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med 345:1388–1393CrossRefPubMedGoogle Scholar
  23. 23.
    Moghissi KS, Wallach EE (1983) Unexplained infertility. Fertil Steril 39:5–21PubMedGoogle Scholar
  24. 24.
    van der Steeg JW, Steures P, Eijkemans MJ, Habbema JDF, Hompes PG, Kremer JA et al (2011) Role of semen analysis in subfertile couples. Fertil Steril 95:1013–1019CrossRefPubMedGoogle Scholar
  25. 25.
    Carlsen E, Petersen JH, Andersson AM, Skakkebaek NE (2004) Effects of ejaculatory frequency and season on variations in semen quality. Fertil Steril 82:358–366CrossRefPubMedGoogle Scholar
  26. 26.
    Castilla JA, Alvarez C, Aguilar J, González-Varea C, Gonzalvo MC, Martínez L (2006) Influence of analytical and biological variation on the clinical interpretation of seminal parameters. Hum Reprod 21:847–851CrossRefPubMedGoogle Scholar
  27. 27.
    Alvarez C, Castilla JA, Martínez L, Ramírez JP, Vergara F, Gaforio JJ (2003) Biological variation of seminal parameters in healthy subjects. Hum Reprod 18:2082–2088CrossRefPubMedGoogle Scholar
  28. 28.
    Keel BA (2006) Within- and between-subject variation in semen parameters in infertile men and normal semen donors. Fertil Steril 85:128–134CrossRefPubMedGoogle Scholar
  29. 29.
    Poland ML, Moghissi KS, Giblin PT, Ager JW, Olson JM (1985) Variation of semen measures within normal men. Fertil Steril 44:396–400PubMedGoogle Scholar
  30. 30.
    Baker HW, Kovacs GT (1985) Spontaneous improvement in semen quality: regression towards the mean. Int J Androl 8:421–426CrossRefPubMedGoogle Scholar
  31. 31.
    Berman NG, Wang C, Paulsen CA (1996) Methodological issues in the analysis of human sperm concentration data. J Androl 17:68–73PubMedGoogle Scholar
  32. 32.
    Agarwal A, Makker K, Sharma R (2008) Clinical relevance of oxidative stress in male factor infertility: an update. Am J Reprod Immunol 59:2–11CrossRefPubMedGoogle Scholar
  33. 33.
    Esteves SC, Sharma RK, Gosálvez J, Agarwal A (2014) A translational medicine appraisal of specialized andrology testing in unexplained male infertility. Int Urol Nephrol 46:1037–1052CrossRefPubMedGoogle Scholar
  34. 34.
    Clinical Laboratories Improvement Amendment 1988 (CLIA). Accessed 1 Aug 2014
  35. 35.
    Alvarez C, Castilla JA, Ramírez JP, Vergara F, Yoldi A, Fernández A et al (2005) External quality control program for semen analysis: Spanish experience. J Assist Reprod Genet 22:379–387PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    Cooper TG, Björndahl L, Vreeburg J, Nieschlag E (2002) Semen analysis and external quality control schemes for semen analysis need global standardization. Int J Androl 25:306–311CrossRefPubMedGoogle Scholar
  37. 37.
    Keel BA, Stembridge TW, Pineda G, Serafy NT Sr (2002) Lack of standardization in performance of the semen analysis among laboratories in the United States. Fertil Steril 78:603–608CrossRefPubMedGoogle Scholar
  38. 38.
    Riddell D, Pacey A, Whittington K (2005) Lack of compliance by UK andrology laboratories with World Health Organization recommendations for sperm morphology assessment. Hum Reprod 20:3441–3445CrossRefPubMedGoogle Scholar
  39. 39.
    Snow-Lisy D, Sabanegh E Jr (2013) What does the clinician need from an andrology laboratory? Front Biosci (Elite Ed) 5:289–304Google Scholar
  40. 40.
    Trost LW, Nehra A (2011) Guideline-based management of male infertility: Why do we need it? Indian J Urol 27:49–57PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Atkins D, Best D, Briss PA et al (2004) GRADE Working Group. grading quality of evidence and strength of recommendations. BMJ 2328(7454):1490Google Scholar
  42. 42.
    European Association of Urology (EAU) (2012). Guidelines office manual. Accessed 31 July 2014
  43. 43.
    Guyatt GH, Oxman AD, Vist GE et al (2008) GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 336(7650):924–926PubMedCentralCrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.ANDROFERT, Andrology and Human Reproduction ClinicCampinasBrazil
  2. 2.McGill University Health CenterMontrealCanada

Personalised recommendations