Azoospermia: etiology, pathogenesis, prevalence of forms and algorithm for differential diagnostics
Abstract
Introduction . Azoospermia, defined as the absence of spermatozoa in the ejaculate after centrifugation, is one of the leading causes of male infertility, affecting approximately 1,0 % of men in the general population and up to 15,0 % of infertile patients. Timely differentiation between obstructive (ОА) and non-obstructive (NOA) azoospermia is critical for selecting appropriate treatment strategies, determining prognosis, and applying assisted reproductive technologies (ART). Aim : to investigate the prevalence of different azoospermia forms of azoospermia in infertile men, within the context of real-world clinical practice at a non-specialized endocrine outpatient department, including personal observations, with consideration of/in comparison with the results of international and Russian epidemiological studies. Materials and Methods . A comprehensive analysis of literature, clinical guidelines, and original data was performed. The study included 450 men aged 25–45 years with confirmed azoospermia. All patients underwent a comprehensive examination, including collection of anamnesis (reproductive, somatic, surgical); physical examination with assessment of secondary sexual characteristics, size and consistency of the testicles; double examination of ejaculate (centrifugation, microscopy); examination of blood hormone levels (follicle-stimulating hormone, luteinizing hormone, total testosterone, prolactin, anti-Müllerian hormone, sex hormone-binding globulin, inhibin B; if indicated – estradiol, thyroid-stimulating hormone, thyroxine); scrotum ultrasound examination with Doppler ultrasonography; genetic testing – karyotyping, testing for microdeletions of Y chromosome azoospermia factor ( AZF ) of the Y chromosome, CFTR (cystic fibrosis transmembrane conductance regulator) gene testing; when indicated, testicular sperm extraction (TESE) biopsy was performed. Results . NOA and OA were identified in 63.3 % and 30 % of patients, respectively. Among NOA cases, the leading causes were idiopathic forms (19.6 %), Klinefelter syndrome (8.4 %), Y-chromosome microdeletions (5.8 %), and hypogonadotropic hypogonadism (6.7 %). Varicocele was associated with NOA in 12 % of cases. These findings are consistent with global data, although minor ethnic and methodological differences were observed. Conclusion . Azoospermia is a clinically and etiologically heterogeneous condition. Timely differentiation between its forms and the inclusion of genetic testing improve diagnostic accuracy and help optimizing management strategies. Standardization of diagnostic algorithms and a personalized approach increase ART effectiveness and the likelihood of fertility restoration.