How to evaluate azoospermia?

Evaluation of Azoospermia

The initial evaluation for azoospermia should include a physical examination performed by an examiner with appropriate training and expertise, a reproductive history, and at least two properly performed semen analyses. 1

Initial Diagnostic Approach

Semen Analysis

• Perform at least two semen analyses at least one month apart to confirm azoospermia 1
• Patients should abstain from sexual activity for 2-3 days before collection 1
• Specimens should be kept at room or body temperature during transport and examined within one hour of collection 1
• Centrifugation of the specimen is necessary to confirm complete absence of sperm 2

Physical Examination

• Evaluate testicular size and consistency (testicular long axis >4.6 cm suggests obstructive azoospermia) 3
• Assess for presence of vasa deferentia (congenital bilateral absence can be diagnosed by physical examination) 1
• Check for varicocele, hydrocele, or other scrotal abnormalities 1
• Evaluate secondary sex characteristics, including hair distribution and breast development 1
• Perform digital rectal examination to assess prostate 1

Hormonal Evaluation

• Measure serum testosterone and follicle-stimulating hormone (FSH) levels 1
• FSH levels are negatively correlated with the number of spermatogonia 1
• FSH >7.6 mIU/mL suggests non-obstructive azoospermia 3
• Consider measuring luteinizing hormone (LH) as part of basic hormonal workup 1
• Some experts recommend anti-Müllerian hormone (AMH) testing as lower levels may predict better sperm retrieval outcomes 1

Distinguishing Obstructive vs. Non-obstructive Azoospermia

Indicators of Obstructive Azoospermia

• Normal FSH levels (≤7.6 mIU/mL) 3
• Normal testicular size (long axis >4.6 cm) 3
• Low ejaculate volume (<1.5 mL) may suggest ejaculatory duct obstruction or congenital bilateral absence of vas deferens 1

Indicators of Non-obstructive Azoospermia

• Elevated FSH levels (>7.6 mIU/mL) 3
• Small testicular size (long axis ≤4.6 cm) 3
• History of cryptorchidism, testicular trauma, or chemotherapy 2

Additional Testing

Post-ejaculatory Urinalysis

• Indicated when ejaculate volume is <1 mL (except in patients with bilateral vasal agenesis or hypogonadism) 1
• Helps diagnose retrograde ejaculation 1, 4

Imaging Studies

• Transrectal ultrasonography (TRUS) is indicated in azoospermic patients with palpable vasa and low ejaculate volumes to evaluate for ejaculatory duct obstruction 1
• Scrotal ultrasonography is indicated when physical examination of the scrotum is difficult or inadequate, or when a testicular mass is suspected 1

Genetic Testing

• Karyotype testing is recommended for patients with azoospermia or severe oligospermia (<5 million/mL) 1, 4
• Y-chromosome microdeletion analysis is mandatory for those with azoospermia or sperm concentration <1 million/mL 1
• Cystic fibrosis transmembrane conductance regulator (CFTR) gene testing should be offered to female partners of men with congenital bilateral absence of vas deferens 1

Testicular Biopsy

• Isolated diagnostic testicular biopsy is rarely indicated in modern practice 3
• Therapeutic testicular biopsy with sperm extraction is preferred for men with presumed non-obstructive azoospermia who accept advanced reproductive treatment 3
• Microdissection testicular sperm extraction (mTESE) has shown higher sperm retrieval rates compared to conventional TESE 4

Important Considerations

• FSH levels alone cannot definitively predict sperm retrieval success in all cases, as men with maturation arrest on histology can have normal FSH despite severe spermatogenic dysfunction 1, 5
• Genetic abnormalities are more common in men with severe spermatogenic dysfunction, with potential implications for offspring 4
• Before proceeding with intracytoplasmic sperm injection (ICSI), patients should be informed about potential genetic abnormalities associated with azoospermia 1, 4
• Testosterone replacement therapy should be avoided in men desiring fertility as it can suppress spermatogenesis 4, 5