What are the steps for a male infertility evaluation?

Male Infertility Evaluation

The initial evaluation of male infertility requires a reproductive history, focused physical examination, and two semen analyses performed at least one month apart, with endocrine evaluation indicated for abnormal results, particularly when sperm concentration is below 10 million/mL. 1, 2

When to Initiate Evaluation

• Perform evaluation after 12 months of unprotected intercourse without conception 1
• Initiate evaluation earlier if male risk factors exist (history of bilateral cryptorchidism, varicocele, prior surgeries, gonadotoxin exposure) 1
• Evaluate immediately if the female partner is over 35 years old 1
• Men concerned about fertility status without a current partner should undergo evaluation 1

Reproductive History Components

The history must specifically assess 1:

• Frequency and timing of intercourse (inadequate timing is a correctable factor)
• Prior fertility history and duration of current infertility
• Childhood illnesses and developmental history (cryptorchidism, delayed puberty)
• Systemic illnesses and previous surgeries (hernia repairs, orchiopexy)
• Sexual history including sexually transmitted diseases
• Gonadotoxin exposure: heat exposure (hot tubs, laptops), anabolic steroids, chemotherapy, radiation 1, 2
• Prescription and non-prescription drug use (testosterone products, antihypertensives, psychiatric medications)
• Family reproductive history

Physical Examination Specifics

The genital examination must include 1, 3:

• Penis examination: location of urethral meatus (hypospadias assessment)
• Testicular measurement and palpation: normal adult testes measure ≥20 mL volume or ≥4 cm length; small, firm testes suggest primary testicular failure 1, 4
• Vas deferens and epididymides: presence and consistency; absence indicates congenital bilateral absence of vas deferens (CBAVD), which can be definitively diagnosed on physical examination 1
• Varicocele assessment: palpable abnormality affecting sperm production, examined while standing with Valsalva maneuver 2
• Secondary sex characteristics: body habitus, hair distribution, breast development (gynecomastia suggests hormonal abnormalities) 1
• Digital rectal examination 1

Semen Analysis Protocol

Two semen analyses are mandatory, performed at least one month apart 1, 2:

Collection Instructions

• Abstain from sexual activity for 2-3 days before collection 1, 3
• Collect by masturbation or intercourse using semen collection condoms 1
• If collected at home, keep at room or body temperature during transport 1
• Examine within one hour of collection 1

Reference Parameters (WHO criteria) 1:

• Volume: 1.5-5.0 mL
• pH: >7.2
• Sperm concentration: >20 million/mL
• Total sperm number: >40 million per ejaculate
• Motility: >50%
• Forward progression: >2 (scale 0-4)
• Normal morphology (varies by WHO vs. Kruger criteria)

If semen analysis is normal, a single test is sufficient; if abnormal on at least two tests, further andrological investigation is indicated 1

Endocrine Evaluation Indications

Perform hormonal assessment when 1, 2:

• Sperm concentration <10 million/mL (mandatory threshold)
• Any abnormal semen parameters on two separate analyses
• Small testicular size on examination
• Clinical signs of hypogonadism

Minimum hormonal panel includes 4:

• Total testosterone
• Follicle-stimulating hormone (FSH)
• Luteinizing hormone (LH)

Genetic Testing Requirements

Mandatory genetic testing for 2:

• Azoospermia or severe oligospermia <5 million/mL: karyotyping and Y-chromosome microdeletion analysis required before considering intracytoplasmic sperm injection (ICSI)
• Congenital bilateral absence of vas deferens: cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation testing

Referral Criteria

Any abnormal semen parameters require referral to a male reproductive specialist for complete evaluation 2. This is critical because:

• Over 50% of male infertility cases stem from specific medical conditions with health implications beyond fertility 2, 3
• Men with abnormal semen parameters have significantly higher rates of testicular cancer and overall mortality compared to fertile men 2, 3
• Most cases of male infertility can be treated and reversed by medical or surgical interventions, avoiding unnecessary assisted reproductive technologies 5

Common Pitfalls to Avoid

• Do not rely on a single semen analysis for diagnosis; variability requires at least two samples 1, 2
• Do not assume semen analysis alone distinguishes fertile from infertile men; it provides important information but cannot definitively predict fertility 1
• Do not delay evaluation in couples where the female partner is over 35 years; time is critical for this population 1
• Do not overlook the broader health implications; male infertility evaluation is an opportunity to identify systemic diseases and cancer risk 2, 3