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Quantitative High-Frequency Ultrasound Identifies Spermatogenesis in Infertile Men with Non-Obstructive Azoospermia

T. Kohn, P. Coady, A. Oppenheimer, A. Walia, B. S. Hernández, J. Kohn, N. Parikh, M. Bazzi et al.

medRxiv, 2026

27 participants

Abstract

Objective: To determine whether quantitative ultrasound (QUS), which characterizes tissue microstructure using radiofrequency data, can identify regional heterogeneity within seminiferous tubules that corresponds to localized spermatogenesis in men with non-obstructive azoospermia (NOA). Design: Two-cohort study using a biological extremes cohort to establish plausibility of a QUS biomarker, followed by an independent NOA-biopsy cohort with site-matched imaging and tissue sampling. Setting: Academic male fertility referral center. Patients: The biological extremes cohort included fertile men with presumed intact spermatogenesis (n=15) and men with NOA and subsequent negative microdissection testicular sperm extraction (mTESE; n=10). The NOA-biopsy cohort consisted of 27 men with NOA undergoing site-matched testicular biopsy via testicular sperm aspiration (TESA) or testicular sperm extraction (TESE), yielding 12 sperm-positive and 36 sperm-negative biopsy sites. Interventions: High-frequency testicular ultrasound (36 MHz) with acquisition of raw radiofrequency data, allowing objective, quantitative analysis of tissue scattering patterns beyond conventional grayscale imaging. Regions of interest were manually annotated and, in the NOA-biopsy cohort, spatially matched to biopsy locations. Main Outcome Measures: Association between sperm presence at biopsy sites and a pre-specified QUS measure of local tissue heterogeneity: the 75th percentile of a sliding window coefficient of…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 27 participants or records.

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