What is the next step in managing azoospermia (absence of sperm in the semen)?

Management of Azoospermia

The next step in managing azoospermia is to differentiate obstructive from non-obstructive causes through focused physical examination (testicular size/consistency, vas deferens palpation), hormonal evaluation (FSH, testosterone), and genetic testing (karyotype and Y-chromosome microdeletion analysis), which together provide >90% diagnostic accuracy and guide definitive treatment. 1, 2

Initial Diagnostic Differentiation

The critical first step is distinguishing between obstructive azoospermia (OA) and non-obstructive azoospermia (NOA), as these have fundamentally different etiologies and treatments 3, 4:

Physical Examination Findings

• Obstructive azoospermia: Normal-sized, fully descended testes with bilaterally dilated and/or indurated epididymides, palpable vas deferens, low ejaculate volume (<1.5 mL), and acidic semen pH (<7.0) 1, 2
• Non-obstructive azoospermia: Testicular atrophy (small, soft testes) with normal ejaculate volume and pH 2, 5

Hormonal Evaluation

• FSH >7.6 IU/L with testicular atrophy: Strongly suggests NOA (primary testicular failure) 1, 5
• Normal FSH with normal testicular size: Suggests OA 1, 5
• Measure serum testosterone and LH concurrently to identify hypogonadotropic hypogonadism, which is a treatable cause of NOA 1

Mandatory Genetic Testing

Before any sperm retrieval procedure or ICSI, obtain karyotype analysis and Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) for all azoospermic men 2, 6. This provides:

• Prognostic information for sperm retrieval success 3, 4
• Essential genetic counseling data 7
• Critical caveat: Complete AZFa and AZFb deletions have nearly zero likelihood of sperm retrieval and contraindicate testicular sperm extraction 1, 5

Management Based on Etiology

Obstructive Azoospermia Treatment

Microsurgical reconstruction is preferable to sperm retrieval when the female partner has normal fertility potential, as it can restore natural fertility 1, 2:

• Vasovasostomy or vasoepididymostomy for post-vasectomy or acquired obstruction 1, 4
• Transurethral resection of ejaculatory ducts (TURED) if ejaculatory duct obstruction is confirmed by transrectal ultrasound (seminal vesicle diameter >15 mm, ejaculatory duct >2.3 mm, dilated vasal ampulla >6 mm) or if seminal vesicle aspirate reveals sperm 1
• Alternative: Surgical sperm extraction (TESE, TESA, or percutaneous epididymal sperm aspiration) with IVF/ICSI if reconstruction is not feasible 1, 8

Important caveat: Avoid epididymal sperm retrieval if future microsurgical reconstruction might be pursued, as it risks epididymal scarring and obstruction 1

Non-Obstructive Azoospermia Treatment

Medical Management (When Applicable)

• Hypogonadotropic hypogonadism: Treat with hCG (500-2500 IU, 2-3 times weekly) followed by FSH when testosterone normalizes—this can restore spermatogenesis in 75% of men without surgery 2, 6
• Empiric hormonal therapy: The 2024 AUA/ASRM guidelines recognize that selective estrogen receptor modulators (SERMs), aromatase inhibitors, and gonadotropins may be tried before surgical intervention, though supporting data is limited 1, 2, 6
• Never prescribe exogenous testosterone to men desiring fertility—it suppresses spermatogenesis through negative feedback and can cause azoospermia requiring months to years for recovery 1, 6

Surgical Sperm Retrieval

Microdissection testicular sperm extraction (micro-TESE) is the gold standard for NOA, recovering sperm in 30-70% of cases even with elevated FSH 1, 2, 6:

• Micro-TESE is 1.5 times more successful than conventional TESE and 2 times more successful than testicular aspiration 1
• Causes less testosterone suppression than conventional TESE, though testosterone deficiency requiring replacement remains a risk 1, 6
• For NOA, some centers perform simultaneous sperm retrieval with ART because sperm numbers may be limited and may not survive cryopreservation 1
• For OA, cryopreserved and fresh sperm have similar ICSI success rates, allowing sperm retrieval prior to ART 1

Assisted Reproductive Technology Outcomes

Once sperm are retrieved, IVF/ICSI treatment typically achieves a 37% live birth rate per initiated cycle 1, 6:

• Critical prognostic factor: Female partner's age—success rates decline progressively beyond 35 years, which should guide treatment timing discussions 1, 6
• Approximately 12.5% of deliveries involve twins 1

Common Pitfalls to Avoid

• Do not perform routine testicular biopsy for diagnosis—clinical and laboratory findings provide >90% diagnostic accuracy 1, 3
• Do not skip genetic testing—it is mandatory before sperm retrieval or ICSI to provide prognostic information and genetic counseling 2, 6
• Do not use testicular sperm aspiration alone for NOA—micro-TESE has significantly higher success rates 1
• For congenital bilateral absence of vas deferens (CBAVD), test the female partner for CFTR mutations due to high risk of the male being a cystic fibrosis carrier 3, 7