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Semen analysis as per WHO 2010
and clinical implications Sandro C. Esteves, MD, PhD
Medical Director, ANDROFERT Campinas, Brazil
Andrology Workshop ISAR 2015 – Chennai
Agenda
Semen analysis overview
New WHO reference values
Implications to clinical management
Proposal of a new report template
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 2 2015
ANDROFERT
Semen analysis is the most used biomarker to predict fertility potential
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 3 2015
ANDROFERT
Routine Semen Analysis
l Physical characteristics of ejaculate l Sperm count l Sperm motility l Sperm morphology l Sperm vitality l Leukocyte count l Additional tests (fructose, etc)
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 4 2015
ANDROFERT
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION
S ESTEVES, 5 2015
ANDROFERT
l Standardization Pre-analytical Analytical Post-analytical
l Quality Control Certification, Validation
l Reference values WHO Manual
Where to do it?
l Pre-analytical Instructions for collection Rejection criteria Abstinence period
l Analytical Standard operating procedures
l Post-analytical Report
Is the lab good enough?
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 6 2015
ANDROFERT
SOP format -‐ Clinical and Laboratory Standards Institute (CLSI)
I. General informa3on: • Document number • Revision number and date • Effec3ve date of the document • Number of pages • Title, to include name of analyte, type of specimen, and method/assay and/or instrumenta3on • Principle and/or purpose • Scope II. Pre-‐analy3c informa3on: • Specimen requirements/collec3on methods III. Analy3c informa3on: • Reagents, standards, controls, and media used • Instrumenta3on, Calibra3on procedures • QC (nega3ve/posi3ve control if required) • Procedural steps • AMachments (e.g., product inserts)
IV. Post-‐analy3c informa3on: • Calcula3ons • Repor3ng results • Reference ranges/cri3cal values • Limita3ons • References V. Other: • Defini3ons • Distribu3on • Author • Approval signatures and dates • Document change history
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 7 2015
ANDROFERT
Report format - CLSI • Either the par3cipant’s name and/or a unique par3cipant iden3fier • Name and address of laboratory loca3on • Date and 3me of specimen receipt into the laboratory • Assay report date • Name of the test performed • Specimen source (e.g., semen) • Assay result and, if applicable, units of measurement and/or
interpreta3on • Reference ranges • Any informa3on regarding the condi3on and disposi3on of
specimens that do not meet • Laboratory's criteria for acceptability • Records and dates of all assays performed • The iden3ty of the personnel who performed the test(s)
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 8 2015
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WHO Manual: it is free!
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 10 2015
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1980 1987 1992 1999 Volume (mL) ND ≥2 ≥2 ≥2 Count (106/mL) 20-200 ≥20 ≥20 ≥20 Total count (106) ND ≥40 ≥40 ≥40 Motility (%) ≥ 60 ≥50 ≥50 ≥50 Progressive (%) ≥ 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); Esteves et al. Urology 2012
WHO reference values changed
2010 ≥1.5 ≥15 ≥39 ≥40
≥32% ≥58 ≥4* 1.0
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 11 2015
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Urology 2012; 79(1):16-22
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 12 2015
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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 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.
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 13 2015
ANDROFERT
Percentile 5% 50%* 95% Volume (mL) 1.5 3.7 6.8 Count (x106/mL) 15.0 73.0 213.0 Total count (x106) 39.0 255.0 802.0 % Motile 40 61 78 % Progressive motility 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 Reprod Update 16: 231-245, 2010
How the references were obtained
Critical Appraisal of the WHO New Reference Values for Human Semen and Impact on Diagnosis and Treatment of Subfertile Men
Esteves, Zini, Aziz et al, Urology, in press
Columbia USA
Melbourne Australia
Turku Finland
Oslo Norway
Edimburgh UK
Paris France
Copenhagen Denmark
Esteves, 15
WHO 2010: What changed?
• Percentile “5” to determine lower cutoff limits • Strict (Kruger) morphology • Single specimen per individual
Method
• Recent fathers (known TTP) • Limited geographic location
Studied population
Esteves et al. Critical Appraisal of the WHO New Reference Values for Human Semen and Impact on Diagnosis and Treatment of Subfertile Men. Urology 2012; 79(1):16-22.
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 16 2015
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How do the new references impact clinical management?
Referral
Treatment
ART
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 17 2015
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Parameters
Patient
Volume (mL) 2.3
Count (106/mL) 16.5 Progressive motility (%) 40
Vitality(%) 65
Morphology (%) 9
Referral Deferment
References
1999 2010
≥ 2 ≥ 1.5
≥ 20 ≥ 15
≥ 50 ≥ 32
≥ 75 ≥ 58
(14) ≥ 4
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 18 2015
ANDROFERT
987 couples with infertility duration > 12 months
Esteves, Int Braz J Urol 2014
53% reclassification due to morphology
Semen Analysis Report
Abnormal
results as per WHO 1999
38.7% Redefined as
“Normal” as per WHO 2010
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 19 2015
ANDROFERT
Cause of infertility in up to 35% men
Guidelines’ recommendation: Palpable (clinical) Abnormal semen parameters
Male Infertility Best Practice Policy Committee - AUA, 2004; European Association of Urology. Guidelines on Male Infertility, 2010.
Varicocele Treatment
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 20 2015
ANDROFERT
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? Fertil Steril 90: 1769-1773, 2008.
P=0.003 P<0.001
Varicocele
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 21 2015
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ICSI IVF & IUI
ART
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 22 2015
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Semen analysis alone should not be used to counseling or treatment indication
l Semen characteristics that discriminate fertile from infertile men not well defined
l Biological variability l Not account for sperm dysfunctions
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 23 2015
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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
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 24 2015
ANDROFERT
Frequency of elevated SDF in men with unexplained infertility
Elevated SDF
(27%)
Androfert; N=987
Elevated SDF (27%)
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 25 2015
ANDROFERT
Proposal for a new report template
Esteves, Int Braz J Urol 2014; 40:443-‐53
ANDROLOGY AND HUMAN REPRODUCTION CLINIC - REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 26 2015
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Thank you धन्यवाद Obrigado
hMp://www.slideshare.net/sandroesteves
