Male Infertility Workup
Initiate evaluation after 12 months of unprotected intercourse in couples where the female partner is under 35 years, or after 6 months if she is 35 years or older—and critically, evaluate both partners simultaneously from the outset, as male factors contribute to 50% of infertility cases. 1, 2
Initial Assessment Components
Reproductive History (Required Elements)
Obtain the following specific information at the first visit:
- Sexual history: Frequency and timing of intercourse, prior fertility with current or previous partners, duration of current infertility 1
- Developmental history: Bilateral cryptorchidism, delayed puberty, childhood illnesses 1, 3
- Medical conditions: Systemic illnesses, previous surgeries (especially inguinal or scrotal), sexually transmitted diseases 1
- Gonadotoxin exposure: Anabolic steroid use (critical—causes azoospermia), heat exposure (saunas, hot tubs, laptops), occupational exposures, chemotherapy 1, 2
- Medications: Current prescription and non-prescription drugs, particularly testosterone products which completely suppress spermatogenesis 1, 4
- Family history: Reproductive disorders, genetic conditions 1
Physical Examination (Specific Findings to Document)
Perform a focused genital examination documenting:
- Penile examination: Location of urethral meatus, presence of hypospadias 1, 3
- Testicular assessment: Measure testicular volume (normal >15 mL), assess consistency and symmetry 1, 3
- Vas deferens and epididymides: Palpate for presence and consistency—congenital bilateral absence of vas deferentia can be diagnosed on physical examination alone 1, 3
- Varicocele detection: Check for palpable varicocele, which affects sperm production and quality 1, 2
- Secondary sex characteristics: Evaluate body habitus, hair distribution, breast development (gynecomastia suggests hormonal abnormalities) 1, 3
- Digital rectal examination: Assess prostate and seminal vesicles 1, 3
Semen Analysis Protocol
Order at least two semen analyses separated by one month to confirm persistent abnormalities, as semen parameters are highly variable biological measures. 1, 4
Collection Instructions
- Abstinence period: 2-3 days before collection 1, 4
- Collection method: Masturbation or intercourse using semen collection condoms (avoid vaginal lubricants as they reduce fertility) 1, 4
- Transport: Keep specimen at room or body temperature, examine within 1 hour of collection 1
- Location: Use specialized andrology laboratory—point-of-care and mail-in tests cannot substitute for comprehensive laboratory analysis 1
WHO Reference Values (5th Percentile Lower Limits)
- Volume: ≥1.5 mL 1
- pH: ≥7.2 1
- Sperm concentration: ≥20 million/mL (some sources use ≥15 million/mL) 1
- Total motility: ≥40% 1
- Progressive motility: ≥32% 1
- Normal morphology: ≥4% (strict criteria) 1
Critical caveat: Semen analysis alone cannot distinguish fertile from infertile men—clinical context is essential. 1, 3
Hormonal Evaluation
Measure serum FSH, LH, and total testosterone in all men with abnormal semen parameters to identify correctable endocrine causes. 1, 4, 5
Interpretation Algorithm
- Gonadotropin deficiency: Low testosterone with low or inappropriately normal LH/FSH—highly treatable with gonadotropin therapy 5
- Primary testicular failure: Low testosterone with elevated LH/FSH 5
- Spermatogenic failure: Normal testosterone and LH with elevated FSH 5
- Androgen resistance: High testosterone with elevated LH 5
Genetic Testing Indications
Order karyotype and Y-chromosome microdeletion analysis before considering ICSI in men with: 1, 2, 4, 5
- Azoospermia (no sperm in ejaculate)
- Severe oligospermia (<5 million/mL)
- Sperm concentration <10 million/mL
Test for cystic fibrosis transmembrane conductance regulator (CFTR) mutations in men with congenital bilateral absence of vas deferentia. 5
Additional Testing in Select Cases
Oxidative Stress Assessment
Consider oxidative stress evaluation in men with unexplained abnormal semen parameters, as it affects sperm DNA integrity and is associated with fertilization failure, poor embryo development, and miscarriage. 1 However, do not routinely measure reactive oxygen species (ROS) as no standardized testing methods exist. 3
Sperm DNA Fragmentation Testing
Consider in couples with:
- Failed assisted reproductive technology cycles 1
- Recurrent pregnancy losses (two or more) 1
- Unexplained infertility despite normal semen parameters 1
Imaging Studies
- Scrotal ultrasound: For suspected varicocele, testicular masses, or obstruction 1
- Transrectal ultrasound: For suspected ejaculatory duct obstruction in azoospermic men with low semen volume 1
Mandatory Specialist Referral Criteria
Refer to male reproductive specialist (urologist or andrologist) for: 2, 4
- Any abnormal semen parameters on two analyses
- Azoospermia or severe oligospermia (<5 million/mL)
- Sperm concentration <10 million/mL
- Palpable varicocele with abnormal semen parameters
- Abnormal hormonal profile
- Suspected obstruction
- Failed assisted reproductive technology cycles
Critical Health Implications Beyond Fertility
Men with abnormal semen parameters have significantly higher rates of testicular cancer and overall mortality compared to fertile men—over 50% of male infertility cases stem from specific medical conditions with health implications beyond fertility. 2, 3, 4 This makes thorough evaluation critical for the patient's overall health, not just reproductive potential.
Common Pitfalls to Avoid
- Never prescribe testosterone to men desiring fertility—it causes complete suppression of spermatogenesis through negative feedback and induces azoospermia 1, 4
- Do not rely on a single semen analysis—at least two samples one month apart are required due to high biological variability 1
- Never evaluate only one partner—simultaneous evaluation is mandatory as 50% of cases involve male factors 1
- Do not delay female partner evaluation while treating male factor, as female age critically impacts outcomes 4
- Avoid prolonged empiric medical therapy—if no improvement after 3-6 months, advance to assisted reproductive technologies 4
Lifestyle Modification Counseling
Discuss and document counseling on modifiable risk factors: 1, 4
- Smoking cessation: Impairs sperm quality and increases oxidative stress
- Alcohol limitation: Excessive intake reduces fertility
- Avoid recreational drugs: Cannabis, cocaine, and opioids impair spermatogenesis
- Heat avoidance: Limit hot tub use, saunas, and laptop placement on lap
- Weight optimization: Both obesity and extreme thinness reduce fertility rates
- Avoid vaginal lubricants: Most commercially available products reduce sperm motility