The document discusses the new WHO standards for semen analysis from 2010. It provides the following key points: 1. The new standards are based on semen samples from 1,953 men in committed relationships whose partners conceived within 12 months. 2. Reference values were established using the 5th percentile cut-off of semen parameters from these men across multiple studies in different world regions. 3. While the new standards provide a global reference, the studies used were not evenly distributed worldwide and some regions were under-represented.

1. Training Program in Assisted Reproductive Technology 2011 Cleveland Clinic Reproductive Research CenterNew WHO Standards for Semen Analysis: Highlights and ImplicationsSandroEsteves, MD, PhDDirectorANDROFERTCenter for Male Reproduction and InfertilityCampinas, BRAZIL

2. Learning ObjectivesEsteves, 2

3. Semen AnalysisEsteves, 3

4. Cut-off reference values for semen characteristics as published in consecutive WHO manuals*Strict (Tygerberg) criterion

5. New WHO StandardsHow they were obtained 1,953 semen samples of recent fathersTime to pregnancy (TTP) ≤ 12 mo5 studies in 7 countries on 3 continentsLaboratories with QC onlyMorphology by strict criterion (Kruger)Progressive and non-progressive motilityLower reference limits (5th centile)Esteves, 5

6. Percentile distribution of semen characteristics values of recent fathers whose partners had a TTP ≤ 12 months, used to establish the reference limits in the 2010 WHO manualCooper et al: World Health Organization reference values for human semen characteristics. Hum Reprod Update 16: 231-245, 2010Esteves, 6

7. New WHO StandardsHow they were obtained Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker H, Behre H, Haugen T, Kruger T, Wang C, Mibzvo MT, Vogelsong KWorld Health Organization reference values for human semen characteristics. Hum Reprod Update 16: 231-245, 2010. “Studies were conducted in different regions of the world with some areas over-represented, such as Northern Europe, and others, such as Africa, parts of Europe and Central and South America, under-represented”“The values presented are considered to represent global semen characteristics of fertile men”Esteves, 7

8. New WHO Standards

9. New WHO references valuesCritical Appraisal FINLAND(Turku)NORWAY(Oslo)DENMARK (Copenhagen)UK(Edinburgh)USA(Columbia, NYC, Minneapolis, LA)?FRANCE(Paris)?????AUSTRALIA (Melbourne)Esteves, 9

10. Studies used to establish the new standards for human semen characteristics in the 5th ed. WHO ManualEsteves, 10

11. New WHO StandardsCritical Appraisal - SummaryEsteves, 11

12. Female Partner Influence on the Potential Fertility of a ManEsteves, 12

13. Referrals for male partner evaluationNew WHO StandardsImplications for Clinical PracticeVaricocele treatmentIndications for assisted reproductive techniquesEsteves, 13

14. Implications for PracticeReferrals for male partner evaluationEsteves, 14

15. Implications for PracticeReclassification of semen analysis reportsCouples (N=987) with infertility duration > 12 monthsMorphology results accounted for 53% of reclassificationSource: ANDROFERT, BrazilEsteves, 15

16. Male Infertility Evaluation – much more than a simple semen analysis - Esteves, 16

17. Implications for PracticeVaricocele treatmentEsteves, 17

18. Implications for PracticeVaricocele treatmentKamal KM, Jarvi K, Zini A: Microsurgical varicocelectomy in the era of assisted reproductive technology: influence of initial semen quality on pregnancy rates. FertilSteril 75: 1013-1016, 2001.Richardson I, Grotas AB, Nagler HM: Outcomes of varicocelectomy treatment: an updated critical analysis. UrolClin North Am 35:191-209, 2008.

19. P=0.003P<0.001Mori et al. Does varicocele grade determine extent of alteration to spermatogenesis in adolescents? FertilSteril 90: 1769-1773, 2008.Esteves, 19

20. ICSISevere male factor infertilitySemen analysis results fall below new reference limits Implications for PracticeIndications for ART

21. < 5% strict morphology thresholds currently used

22. Indications unlike to change due to new WHO reference valuesEsteves, 20

23. IUIMild male factor infertility

24. Unexplained male infertilityImplications for PracticeIndications for ART

25. Impact of new WHO reference values likely to be minimalEsteves, 21