What are the steps for male fertility testing and treatment?

Male Fertility Testing and Treatment: A Structured Approach

Initial Evaluation

Both partners should undergo concurrent fertility assessment when a couple has not achieved pregnancy after 12 months of unprotected intercourse (or 6 months if the female partner is over 35 years old). 1

Step 1: Reproductive History

The male evaluation must include a comprehensive reproductive history covering: 1

• Sexual history: Frequency and timing of intercourse, prior fertility history, duration of current infertility 1
• Medical history: Childhood illnesses (especially cryptorchidism), developmental history, systemic illnesses, previous surgeries, sexually transmitted diseases 1
• Medication and exposure history: Prescription and non-prescription drug use (particularly anabolic steroids which suppress spermatogenesis), gonadal toxin exposure including heat 1
• Family history: Family reproductive history to identify genetic factors 1

Step 2: Physical Examination

The physical examination should specifically assess: 1

• Penis: Location of urethral meatus 1
• Testes: Measurement and palpation for size and consistency 1
• Vasa deferentia and epididymides: Presence and consistency (congenital bilateral absence of vasa can be diagnosed definitively on physical exam) 1
• Varicocele: Presence or absence 1
• Secondary sex characteristics: Body habitus, hair distribution, breast development 1
• Digital rectal examination: To assess prostate and seminal vesicles 1

Step 3: Semen Analysis

At least one semen analysis is required for initial evaluation, with a second confirmatory analysis performed at least one month later if abnormalities are detected. 1, 2

Collection Requirements:

• Abstinence period: 2-3 days before collection 2
• Collection method: Masturbation or specialized semen collection condoms 2
• Transport: Keep at room or body temperature if collected at home 2
• Timing: Examine within one hour of collection 2

Reference Values (WHO Lower Limits):

• Volume: ≥1.4 mL (range 1.3-1.5 mL) 2
• pH: >7.2 1, 2
• Sperm concentration: ≥16 million/mL (range 15-18 million/mL) 2
• Total sperm number: ≥39 million per ejaculate (range 35-40 million) 2
• Progressive motility: ≥30% (range 29-31%) 2
• Total motility: ≥42% (range 40-43%) 2
• Normal morphology: ≥4.0% (range 3.9-4.0%) 2
• Vitality: ≥54% live spermatozoa (range 50-56%) 2

Important caveat: Point-of-care and mail-in semen tests may provide preliminary information, but specialized andrology laboratory testing remains the gold standard for comprehensive evaluation. 1

Advanced Testing: When to Refer to a Male Reproductive Expert

Men with one or more abnormal semen parameters should be evaluated by a male reproductive expert for complete history, physical examination, and directed testing. 1

Hormonal Evaluation

Obtain FSH and testosterone levels in men with: 1

• Impaired libido or erectile dysfunction 1
• Oligozoospermia (sperm concentration <16 million/mL) 1
• Azoospermia (absence of sperm) 1

Additional Testing Based on Findings:

For Low Volume Ejaculate (<1 mL):

• Post-ejaculatory urinalysis: To rule out retrograde ejaculation 1, 2
• Transrectal ultrasonography (TRUS): If azoospermic with palpable vasa and low volume, to assess for ejaculatory duct obstruction 1

For Azoospermia:

• Centrifuge ejaculate: Examine pellet for rare sperm 2
• Karyotype testing: For primary infertility with azoospermia or sperm concentration <5 million/mL when accompanied by elevated FSH or testicular atrophy 2
• Y-chromosome microdeletion testing: Found in 5% of males with sperm concentrations 0-1 million/mL 2

For Severe Oligospermia (<5-10 million/mL):

• Karyotyping and Y-chromosome analysis: Should be offered before intracytoplasmic sperm injection (ICSI) 1
• Genetic counseling: When genetic abnormality is suspected or detected 1

For Congenital Bilateral Absence of Vasa Deferentia:

• Cystic fibrosis gene mutation testing: In both male and female partners (about two-thirds of men with clinical cystic fibrosis have CFTR gene mutations) 1

For Failed ART Cycles or Recurrent Pregnancy Loss (≥2 losses):

• Karyotype testing: Abnormal karyotype linked to poor IVF outcomes 1
• Sperm DNA fragmentation testing: Elevated levels associated with increased miscarriage rates and poor ART outcomes 1

Note on DNA fragmentation: This should not be routinely performed in initial evaluation, but may be considered in specific clinical scenarios as some causes (anti-depressant use, genitourinary infection) are reversible. 1

Scrotal Ultrasonography

Indicated when: 1

• Physical examination of scrotum is difficult or inadequate 1
• Testicular mass is suspected 1

Health Counseling and Risk Factor Modification

Infertile men with abnormal semen parameters should be counseled about associated health risks, as they have higher rates of testicular cancer, overall cancer, and increased mortality compared to fertile men. 1

Lifestyle Factors to Address:

Discuss and counsel on modifiable risk factors, though acknowledge that data on most factors are limited: 1

• Diet: Lower fat and meat intake with more fruits and vegetables may be preferable 1
• Smoking: Low-quality evidence links smoking to small impacts on sperm concentration, motility, and morphology 1
• Obesity: Associated with increased prevalence of azoospermia and oligozoospermia 1
• Anabolic steroid use: Suppresses spermatogenesis and must be discontinued 1
• Heat exposure: Avoid excessive heat to testes 1
• Medication review: Consult specialized databases for reproductive effects of specific medications 1

Advanced Paternal Age Counseling

Couples with male partner age ≥40 years should be advised of increased risk of adverse health outcomes in offspring, including: 1

• De novo gene mutations 1
• Sperm aneuploidy and chromosomal aberrations 1
• Increased risk of schizophrenia and autism 1
• Birth defects and genetically-mediated conditions 1

Genetic counseling may be considered to discuss the low absolute risk but high relative risk of these conditions. 1

Common Pitfalls to Avoid

• Inadequate abstinence period: Significantly affects volume and concentration 2
• Improper collection technique: Can invalidate results 2
• Delayed analysis: Affects motility assessment 2
• Over-reliance on single parameter: Consider the entire semen profile when evaluating fertility potential 2
• Failure to follow WHO standardized procedures: Leads to high variability between laboratories 2
• Single semen analysis in borderline cases: At least 2 analyses one month apart are important when first analysis shows abnormal parameters 1