Novel Diagnostic Algorithm for Azoospermia: The Role of 17-Hydroxyprogesterone and Round Spermatids in Normogonadotropic Azoospermia

Normogonadotropic azoospermia (NOAN) represents a diagnostic and therapeutic challenge in male infertility, affecting men with normal gonadotropin levels but absent sperm in the ejaculate. Emerging evidence has identified 17-hydroxyprogesterone (17OHP) as a potential biomarker for detecting reduced intratesticular testosterone (ITT) levels, and the presence of round spermatids in ejaculate as an indicator of residual spermatogenic activity. This report synthesizes current evidence on a proposed hypothesis-generating diagnostic framework that utilizes these markers to guide hormonal treatment strategies. Specifically, patients with elevated 17OHP levels (>1.18 ng/mL) and detectable round spermatids may benefit from combined human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) therapy at doses lower than those used for hypogonadotropic hypogonadism. However, this cutoff has not been prospectively validated in NOAN-specific cohorts, and the evidence supporting this approach remains preliminary, derived from small heterogeneous cohorts. Alternative therapeutic strategies, including FSH monotherapy and non-hormonal pharmacological treatments, are also discussed. This framework requires rigorous prospective validation before clinical implementation.