What are the latest guidelines for ordering and interpreting semen analysis in the evaluation of male infertility?

Guidelines for Ordering and Interpreting Semen Analysis

Order two semen analyses at least one month apart as the initial screening for male infertility evaluation, combined with a reproductive history and physical examination by a trained examiner. 1, 2

When to Order Semen Analysis

Timing of Initial Evaluation:

• Order after 12 months of unprotected intercourse without conception 1
• Order earlier if male risk factors exist (history of cryptorchidism, prior testicular surgery, known varicocele) 1
• Order earlier if female partner is over 35 years old 1
• Order for any man concerned about his fertility status, even without a current partner 1

Collection Instructions (Critical for Valid Results)

Pre-Collection Requirements:

• Instruct patient to abstain from sexual activity for 2-3 days before collection 1, 2
• Inadequate abstinence period significantly affects volume and concentration, invalidating results 2

Collection Method:

• Collect by masturbation or intercourse using specialized semen collection condoms (not regular condoms) 1, 2
• If collected at home, keep specimen at room or body temperature during transport 1, 2
• Examine within one hour of collection—delayed analysis affects motility assessment 1, 2

Standard Reference Values for Interpretation

Use these WHO-based lower reference limits: 2

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

How Many Tests to Order

Initial Assessment:

• A single properly performed semen analysis is sufficient for initial evaluation if results are normal 1, 2
• If any abnormalities are detected, order a second confirmatory analysis at least one month after the first 1, 2
• Perform tests at least one month apart to account for the 74-day spermatogenic cycle 1

Interpretation Algorithm

Step 1: Assess Volume and pH

• Low volume (<1.4 mL) with acidic pH (<7.0) suggests ejaculatory duct obstruction or absent seminal vesicles 2
• Low volume (<1 mL) regardless of pH: order post-ejaculatory urinalysis to rule out retrograde ejaculation 1, 2

Step 2: Identify Specific Patterns

• Azoospermia (no sperm): Centrifuge sample and examine pellet for rare sperm; differentiate obstructive vs. non-obstructive causes 2
• Severe oligospermia (<5 million/mL): Order genetic testing (karyotype and Y-chromosome microdeletion analysis) 1, 2
• Oligozoospermia (low concentration): Combined with other abnormalities significantly reduces fertility potential 2
• Asthenozoospermia (reduced motility): Assess in combination with other parameters 2
• Teratozoospermia (abnormal morphology): Remember that even fertile men have <4% normal forms 2

Step 3: Evaluate Multiple Parameters Together

• Assessment of combined parameters is a better predictor of fertility than any single parameter 1
• Do not over-rely on a single parameter when evaluating fertility potential 2
• The substantial overlap in semen parameters between fertile and infertile men means results cannot definitively determine fertility status except in extreme cases 1

Mandatory Additional Workup Based on Results

Order endocrine evaluation if: 1

• Sperm concentration <10 million/mL
• Sexual function is impaired
• Clinical findings suggest endocrinopathy
• Minimum tests: serum testosterone and follicle-stimulating hormone (FSH)

Order genetic testing if: 1, 2

• Severe oligospermia (<5 million/mL) or azoospermia: karyotype testing
• Severe oligospermia: Y-chromosome microdeletion testing (found in 5% of males with 0-1 million/mL)

Order post-ejaculatory urinalysis if: 1, 2

• Ejaculate volume <1 mL (except in bilateral vasal agenesis or hypogonadism)

Essential Components of Complete Evaluation

Reproductive History Must Include: 1

• Frequency and timing of intercourse
• Duration of infertility and prior fertility
• Childhood illnesses (especially cryptorchidism, mumps orchitis)
• Systemic illnesses and previous surgeries
• Sexual history including sexually transmitted diseases
• Gonadal toxin exposure (heat, chemicals, radiation)
• Prescription and non-prescription drug use (especially testosterone/anabolic steroids)
• Family reproductive history

Physical Examination Must Assess: 1

• Penis examination including urethral meatus location
• Testicular size (measurement) and consistency
• Presence and consistency of vas deferens and epididymides
• Presence of varicocele
• Body habitus and secondary sex characteristics
• Digital rectal examination

Critical Pitfalls to Avoid

• Laboratory quality: Many laboratories do not adhere to WHO standardized methods, leading to high variability and unreliable results 1, 2
• Improper collection technique: Invalidates all results 2
• Single parameter focus: Fertility assessment requires evaluation of the entire profile 2
• Assuming normal semen analysis equals fertility: 25% of infertility cases remain unexplained despite normal conventional parameters 1
• Ignoring the female partner: Concurrent evaluation is essential as infertility often involves multiple factors 1

When to Refer for Specialist Evaluation

Refer to urologist or male reproduction specialist if: 1

• Abnormal physical examination findings
• Abnormal reproductive or sexual history
• Any abnormal semen analysis parameters
• Unexplained infertility despite normal initial screening
• Persistent infertility after treatment of female factors