The document discusses interpreting semen analysis results and the implications of the 2010 WHO reference values. It summarizes the WHO reference values over time and how the 2010 values changed the parameters and reference populations. The new 2010 values result in many patients being reclassified and can impact referral for treatment, treatment recommendations, and eligibility for assisted reproduction. A comprehensive evaluation is necessary and semen analysis alone should not determine diagnosis or treatment.

1. Interpreting Semen Analysis Results
SandroC. Esteves, MD, PhD
ANDROFERT, Campinas, Brazil
Reproductive Andrology Surgery Workshop II
Reproductive Medicine Unit -JahraHospital -Kuwait 2014

2. Contents
Semen analysis overview
WHO reference values
Implications to clinical management
Proposal of a new report template
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 2
2014 December
ANDROFERT

3. Semen analysis is the most used biomarker to predict fertility potential
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 3
2014 December
ANDROFERT

4. Routine Semen Analysis
Physical characteristics of ejaculate
Sperm count
Sperm motility
Sperm morphology
Sperm vitality
Leukocyte count
Additional tests (fructose, etc)
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 4
2014 December
ANDROFERT

5. Standardization
Pre-analytical
Analytical
Post-analytical
Quality Control
Certification, Validation
Reference values
WHO Manual
Where to do it?
Esteves, 5

6. Pre-analytical
Instructions for collection
Rejection criteria
Abstinence period
Analytical
Standard operating procedures
Post-analytical
Report
Is the lab good enough?
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 6
2014 December
ANDROFERT

7. ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 8
2014 December
ANDROFERT
WHO Manual: it is free!

8. 1980
1987
1992
1999
Volume (mL)
ND
≥ 2
≥ 2
≥ 2
Sperm count (106/mL)
20-200
≥ 20
≥ 20
≥ 20
Totalsperm count (106)
ND
≥ 40
≥ 40
≥ 40
Motility(%)
≥ 60
≥ 50
≥ 50
≥ 50
Progressivemotility(%)
≥ 2
≥ 25%
≥ 25% (a)
≥ 25% (a)
Vitality(%)
ND
≥ 50
≥ 75
≥ 75
Morphology(%)
80,5
≥ 50
≥ 30
(14)*
Leukocytes(106/mL)
< 4.7
< 1.0
< 1.0
< 1.0
*Strict criteria(Tygerberg)
WHO Reference Values2010
≥ 1.5
≥ 15
≥ 39
≥ 40
≥ 32% (a+b)
≥ 58
≥ 4*
1.0
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 9
2014 December
ANDROFERT

9. Urology 2012; 79(1):16-22
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 10
2014 December
ANDROFERT

10. How the references were obtained
1953 specimens
Recent fathers (Time-to-Pregnancy; TTP) ≤ 12 mo.
Data extracted from 5 studies
Laboratories with QC
Morphology by Kruger’s method
Cooper TG, Noonan E, von EckardsteinS, Auger J, Baker H, BehreH, Haugen T, Kruger T, Wang C, MibzvoMT, VogelsongK
World Health Organization reference values for human semen characteristics.
Hum ReprodUpdate 16: 231-245, 2010.
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 11
2014 December
ANDROFERT

11. Percentile
5%
50%*
95%
Volume (mL)
1.5
3.7
6.8
Count (x106/mL)
15.0
73.0
213.0
Totalcount(x106)
39.0
255.0
802.0
% Motile
40
61
78
% Progressivemotility
32
55
72
% Normal(Kruger)
4
15
44
% Alive
58
79
91
Cooper et al: World Health Organization reference values for human semen characteristics.
Hum ReprodUpdate 16: 231-245, 2010
Esteves, 12
How the references were obtained

12. Critical Appraisal of the WHO New Reference Values for Human Semen and Impact on Diagnosis and Treatment of SubfertileMenEsteves, Zini, Aziz et al, Urology, in press
Columbia
USA
Melbourne
Australia
Turku
Finland
Oslo
Norway
Edimburgh
UK
Paris
France
Copenhagen
Denmark
Esteves, 13

13. WHO 2010: What changed?
•Percentile “5” to determine lower cutoff limits
•Strict (Kruger) morphology
•Single specimen per individual
Method
•Recent fathers (known TTP)
•Selection bias
Studied population
Esteveset al. Critical Appraisal of the WHO New Reference Values for Human Semen and Impact on Diagnosis and Treatment of SubfertileMen. Urology2012; 79(1):16-22.
Esteves, 14

14. How do the new references impact clinical management?
Referral
Treatment
ART
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 15
2014 December
ANDROFERT

15. ParametersPatient
Volume (mL)
2,3
Count (106/mL)16,5
Progressivemotility(%)40
Vitality(%)65
Morphology(%)9
Referral Deferment
References
1999
2010
≥ 2
≥ 1.5
≥ 20
≥ 15
≥ 50
≥ 32
≥ 75
≥ 58
(14)
≥ 4
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 16
2014 December
ANDROFERT

16. 987 couples with infertility duration > 12 months
Esteves, IntBrazJ Urol2014
53% reclassification
due to morphology
Semen Analysis Report
Esteves, 17
Abnormal results as per WHO 1999
38.7%
Redefined as “Normal” as per WHO 2010

17. Cause of infertility in up to 35% men
Guidelines’ recommendation:
Palpable (clinical)
Abnormal semen analysis results
Male Infertility Best Practice Policy Committee -AUA, 2004;
European Association of Urology. Guidelines on Male Infertility, 2010.
Varicocele Treatment
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 18
2014 December
ANDROFERT

18. 87.8
49.9
37.4
62.9
56
55.6
8.4
7.3
6.1
No varicocele
Grade 2 Varicocele
Grade 3 Varicocele
Adolescents with and without Varicocele
Count (million/mL)
Progressive motility (% a+b)
Morphology (%)
Mori et al. Does varicocele grade determine extent of alteration to spermatogenesis in adolescents? FertilSteril90: 1769-1773, 2008.
P=0.003
P<0.001
Varicocele
Esteves, 19

19. ICSI
IVF & IUI
ART
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 20
2014 December
ANDROFERT

20. Semen analysis alone should not be used to counseling or treatment indication
Semen characteristics that discriminate fertile from infertile men not well defined
Biological variability
Not account for sperm dysfunctions
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 21
2014 December
ANDROFERT

21. History taking, physical examination, endocrine profile and laboratory sperm function testing are minimum standards
Esteves, et al 2011; 2012; 2014
Male infertility evaluation goes far beyond a simple semen analysis
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 22
2014 December
ANDROFERT

22. Reporting: proposal for a new template

23. Thank You
شكرا
ANDROFERT
androfert.com.br
ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 24
2014 December
ANDROFERT