INTERPRETATION OF SEMEN ANALYSIS: A CLINICAL PROBLEM

DR SERAJODDIN VAHIDI , ANDROLOGY RESEARCH CENTER,

YAZD REPRODUCTIVE SCIENCE INSTITUTE, YAZD , IRAN

INTRODUCTION: ROLE OF MALE PARTNER IN COUPLES INFERTILITY TRENDS OF MALE FACTOR INFERTILITY, AN IMPORTANT CAUSE OF INFERTILITY: A REVIEW OF LITERATURE, KUMAR ET AL, 2015

About 8-12% of couples suffer from infertility worldwide

It varies across regions of the world

Of all infertility cases, approximately 40–50% is due to “male

factor” infertility

Reproduction is a probabilistic system

More viable sperm: greater chance for fertilization

No sperm: absolutely sterile

HISTORY:

John Macleod 1951

First statistical assessment on semen analysis: fertile and infertile

men

(Count, motility and morphology):

Largely overlapping

Substantial range of values (for the aforementioned parameters):

does not discriminate fertile and infertile men

If the parameters is lower than the threshold: probable male

infertility

The converse is not necessary true

Fertility

Infertility

Health Fertility ART success

Disease Infertility ART failure

APPROACH TO MALE INFERTILITY: HOW? BEST PRACTICE GUIDELINES FOR MALE INFERTILITY DIAGNOSIS AND MANAGEMENTS, KIM AND BENTON, 2020.

1- comprehensive past medical history /physical examination

2- Two semen analysis (one month apart)

3- hormonal evaluation (in specific condition)

4- post-ejaculatory urine sample/ TRUS / scrotal sono (based on case

evaluation)

5- Genetic test

WHY TWO SEMEN ANALYSIS? ARE WHO RECOMMENDATIONS TO PERFORM 2 CONSECUTIVE SEMEN ANALYSES FOR RELIABLE DIAGNOSIS OF MALE INFERTILITY STILL VALID? BLICKENSTORFER ET AL 2019

After finding normozoospermia on the initial analysis 27% of the

second semen analyses were pathological

The recommended abstinence for semen collection:

WHO 1999, WHO 2010, WHO 2021: Two – seven days

Campbell urology: one- two days

INTRAINDIVIDUAL VARIATION IN SEMEN QUALITY: PREDICTION OF MALE INFERTILITY BY THE WORLD HEALTH ORGANIZATION LABORATORY MANUAL FOR ASSESSMENT OF SEMEN ANALYSIS: A SYSTEMATIC REVIEW, PATEL ET AL. 2017

Many studies described fluctuations of semen measurement values within the

same individual (day to day)

Cagnacci and colleagues demonstrates the diurnal variation of semen quality:

higher sperm count in the afternoon

Zhang and co-workers discussed that semen quality in the midsummer was found

to be significantly lower when compared to other periods of the year (Seasonal)

DIFFERENT LAB AND DIFFERENT TECHNICIAN:

COMPARISON LOWER REFERENCE LIMITS FOR CHARACTERISTICS BETWEEN WHO 1999, WHO 2010 AND WHO 2021

Parameter WHO 1999 WHO 2010 WHO 2021

Volume <2 ml <1.5 ml <1.5 ml

Sperm

concentration

<20 x 106 /ml <15 x 106 /ml <10 x 106/ml

Total sperm

count

<40 x 106 / per

eja

<39 x 106 / per

eja

<20x 106 / per

eja

Progressive

motility

(rapid+ slow)

<50% <32%

<35%

Rapid motility <25% - <25%

Total motility

(PR+NP)

-

<40%

<40%

Morphology <15% <4% <4%

Viability <50% <58% <40%

NORMAL VALUE: NORMAL THRESHOLD LIMITATIONS OF SEMEN ANALYSIS AS A TEST OF MALE FERTILITY AND ANTICIPATED NEEDS FROM NEWER TESTS, WANG ET AL, 2014

collected data from >4500 men in 14 countries

men with proven fertility whose partners had a time to

pregnancy of < 12 month: reference ranges for semen

parameters

lower reference limit of the 5th percentile= lower threshold

SEMEN ANALYSIS: INDICATOR OF MALE INFERTILITY?

1- Probable male infertility

2- Absolute male infertility

TIME TO PREGNANCY: PROBABLE MALE INFERTILITY SEMEN QUALITY AND TIME TO PREGNANCY: THE LONGITUDINAL INVESTIGATION OF FERTILITY AND THE ENVIRONMENT STUDY, BUCK LOUIS ET AL., 2013

Sperm count, motility and morphology are associated with time to

pregnancy

Abnormal seminal character may lead to increased time to pregnancy

Time to pregnancy is the surrogate marker for fecundity (means absolute

infertility???)

SEMEN ANALYSIS AND ABSOLUTE INFERTILITY:

1- Azoospermia

2- absolute immotile sperms (primary ciliary dyskinesia)

3- Uniform Teratozoospermia: Globozoospermia

ADVANCED SPERM FUNCTIONAL TEST: EXAMPLES DIAGNOSTIC VALUE OF ADVANCED SEMEN ANALYSIS IN EVALUATION OF MALE INFERTILITY, BARBAROSIE ET AL., 2021

1- Sperm DNA fragmentation assessment / ROS MEASURMENT

2- Sperm capacitation assessment

3- Acrosomal reaction

4- Sperm–zona pellucida binding tests

5- Hemi-zona assay

6- Sperm–oocyte penetration assay

7- SPERM ULTRASTRUCTURAL ASSESSMENTS ( MSOME)

IMPORTANCE OF SPERM DNA FRAGMENTATION : PREVALENCE OF HIGH DNA FRAGMENTATION INDEX IN MALE PARTNERS OF UNEXPLAINED INFERTILE COUPLES, OLESZCUK ET AL. 2013

In couples with unexplained infertility (male assessed with semen

analysis), about 25% of male partner may have increased sperm

DFI above 20%.

SPERM DNA FRAGMENTATION: A NEW GUIDELINE FOR CLINICIANS, AGARWAL ET AL, 2020

SPERM DNA FRAGMENTATION ASSESSMENT: THE TESTS SPERM DNA FRAGMENTATION: A NEW GUIDELINE FOR CLINICIANS, AGARWAL ET AL, 2020

1- Tests for DNA injury

TUNEL , SCSA , SCD , COMET

2- Tests for Chromatin compaction evaluation

SCSA , AB , TB , CMA3

REFERRAL TO THE UROLOGIST: INDICATIONS REASONS THAT SHOULD PROMPT A REFERRAL TO A REPRODUCTIVE UROLOGIST: GUIDELINES FOR THE GYNECOLOGIST AND REPRODUCTIVE ENDOCRINOLOGIST, FARBER ET AL, 2019

1- Azoospermia: primary or secondary testicular failure / vasal obstruction

2- oligozoospermia: primary or secondary testicular failure (beginning) /

partial vasal obstruction

3- abnormal motility or morphology: varicocele, hydrocele, other testicular

pathology (testicular tumors)

4- Leukocytospermia: needs for chronic prostatitis assessment and

treatment

5- recurrent pregnancy loss or ART failure ( Sperm DFI?)

REASONS THAT SHOULD PROMPT A REFERRAL TO A REPRODUCTIVE UROLOGIST: GUIDELINES FOR THE GYNECOLOGIST AND REPRODUCTIVE ENDOCRINOLOGIST, FARBER ET AL, 2019

Male factor infertility :barometer for general health.

Particularly in cases of idiopathic infertility, an underlying comorbid

condition may be responsible for impaired spermatogenesis

A literature review by Choy and Eisenberg even posits a link between male

infertility and various other oncologic, metabolic, and auto-immune

processes (22% in infertile men in comparison with 9% fertile man)

CONCLUSION

SEMEN ANALYSIS IS THE CORNER STONE TEST IN ANDROLOGY CLINICS

BUT IT HAS SOME SHORTCOMINGS:

1- DIFFERENT STANDARDS

2- DIFFERENT LAB AND TECHNICIAN

3- INTRAINDIVIDUAL , DIURNAL, INTERSEASONAL VARIATION

4- INSUFFICIENCY FOR INTERPRETATION OF SPERM FUNCTIONS

5- INABILITY TO DIFFERENTIATE BETWEEN FERTILITY AND INFERTILITY

SEMEN ANALYSIS ONCE WAS THE CORNER STONE IN ANDROLOGY CLINICS , NOW HAS BEEN SUPPLANTED WITH MORE ADVANCE SPERM FUNCTIONAL TESTS IN SPECIFIC CONDITIONS

Thanks for your attention