1. Training Program in Assisted Reproductive Technology 2011 Cleveland Clinic Reproductive Research Center New WHO Standards for Semen Analysis: Highlights and Implications SandroEsteves, MD, PhD Director ANDROFERT Center for Male Reproduction and Infertility Campinas, BRAZIL

2. Learning Objectives Esteves, 2

3. Semen Analysis Esteves, 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 fathers Time to pregnancy (TTP) ≤ 12 mo 5 studies in 7 countries on 3 continents Laboratories with QC only Morphology by strict criterion (Kruger) Progressive and non-progressive motility Lower 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 manual Cooper et al: World Health Organization reference values for human semen characteristics. Hum Reprod Update 16: 231-245, 2010 Esteves, 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 K World 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 Manual Esteves, 10

11. New WHO StandardsCritical Appraisal - Summary Esteves, 11

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

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

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

21. < 5% strict morphology thresholds currently used

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

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

28. Practical Points (1) Esteves, 24

29. Practical Points (2) Esteves, 25