Histological, Genetic, and Endocrine Markers of Non-Obstructive Azoospermia

Azoospermia is defined as the absence of spermatozoa in the ejaculate after centrifugation. This condition represents one of the most severe causes of male infertility. The prevalence of azoospermia is up to 1% among men in the general population and up to 10–15% among patients with impaired fertility (Kaltsas et al., 2024). Azoospermia is not an independent disease but rather a symptom complex indicating profound disturbances in the male reproductive system, and identifying the causes of this condition in each individual case may become a tool for its correction. In terms of its pathogenesis, the non-obstructive form of this condition (NOA) is prognostically unfavorable. Spermatozoa are not produced because of hormonal or genetic abnormalities. Assessment of sex hormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, in patients with NOA is clearly insufficient for predicting the retrieval of autologous spermatozoa during testicular biopsy. Therefore, the identification of reliable markers of NOA is one of the key challenges in cell biology and andrology. The aim of this review is to systematize current data on the histological patterns of NOA, their cellular and endocrine mechanisms, and to evaluate their association with existing and emerging predictors of successful testicular biopsy.