Micro-TESE in Non-Obstructive Azoospermia: Phenotype-Guided Hormonal Optimization and Testosterone Response—Prognostic Biomarker or Therapeutic Target?

Non-obstructive azoospermia (NOA) is the most severe phenotype of male-factor infertility and reflects impaired spermatogenesis rather than ductal obstruction. Microdissection testicular sperm extraction (micro-TESE) is the primary sperm retrieval method, but sperm retrieval rates remain at approximately 40–60% and vary with etiology, genetics, histopathology, surgical expertise, and endocrine phenotype. This narrative review synthesizes major international and regional guidelines and contemporary evidence on preoperative hormonal optimization, with particular emphasis on endogenous testosterone dynamics. Exogenous testosterone is contraindicated in fertility-seeking men because it suppresses gonadotropins and intratesticular testosterone. By contrast, selective estrogen receptor modulators, aromatase inhibitors, human chorionic gonadotropin, and follicle-stimulating hormone aim to preserve or augment endogenous Leydig- and Sertoli-cell function. Low-certainty, predominantly observational evidence suggests an association between hormonal pretreatment and higher sperm retrieval in selected normogonadotropic or hypogonadal men, but not consistently in hypergonadotropic NOA. A larger testosterone rise during stimulation has been positively associated with retrieval and may reflect residual Leydig-cell reserve, although causality and transferable thresholds remain unproven. Preoperative endocrine therapy should therefore remain individualized, phenotype-guided, off-label, closely monitored, and preferably investigated within clinical trials; the testosterone response is best regarded as a candidate prognostic biomarker rather than a validated therapeutic target or decision rule.