How should non-obstructive azoospermia be managed?

[Verified against AUA/ASRM Male Infertility Guideline 2021] Categorisation first. Azoospermic men should be clinically evaluated to differentiate genital tract obstruction from impaired sperm production, based initially on semen volume, physical examination and FSH (Expert Opinion). Small testes with elevated FSH and normal semen volume typically indicate NOA. Normal testis volume (length over 4.6 cm), FSH under 7.6 and semen volume under 0.5–1.0 mL suggests obstruction, particularly with an enlarged proximal epididymis or absent vasa. Diagnostic testicular biopsy should not routinely be performed to make this distinction (Expert Opinion). Genetic testing before any surgical plan. Karyotype and Y-microdeletion analysis (Expert Opinion). Complete AZFa and/or AZFb deletion means sperm have not been retrieved by TESE and surgical intervention is not indicated. This determination should precede offering retrieval, not follow it. Retrieval. Micro-TESE should be performed for men with NOA undergoing sperm retrieval (Moderate Recommendation, Grade C) — 1.5 times more successful than non-microsurgical TESE. Medical therapy before retrieval. SERMs, aromatase inhibitors and hCG have been used off-label to try to improve retrieval rates. The guideline is direct: for men with NOA, such medical interventions have limited, low-quality data available to support any treatment benefit. Studies have typically been uncontrolled, and it is unclear whether the drug, more careful examination of the centrifuged specimen, or simply repeated attempts accounted for apparent success. Before concluding azoospermia at all: extended search of the centrifuged pellet found at least rare sperm in up to 35% of men previously thought azoospermic. That is worth doing before any surgical discussion.