Global Andrology Forum (GAF) Clinical Guidelines on the Management of Non-obstructive Azoospermia: Bridging the Gap between Controversy and Consensus

Abstract

Purpose: Non-obstructive azoospermia (NOA), defined as the absence of sperm in the ejaculate due to testicular failure, is observed in 5% to 15% of infertile men and accounts for two-thirds of azoospermia cases. The management of NOA is marked by significant controversy and global variation in diagnostic and therapeutic approaches, highlighting the crucial need for well-designed and standardized clinical practice guidelines. We present comprehensive graded clinical practice recommendations and statements for diagnosing and treating NOA, aiming to establish standardized strategies that can globally help guide practitioners in their practice.

Materials and methods: A comprehensive literature review was conducted to gather evidence on the epidemiological, diagnostic, and therapeutic aspects of NOA. The Global Andrology Forum (GAF) recommendations were developed through the collaboration of a global panel of experts using the Delphi method and surveys to achieve consensus. Statements were graded according to the Oxford Centre for Evidence-Based Medicine "GRADE" classification as either "Strong" or "Weak." Statements receiving at least 80% expert consensus were graded as "Strong," while others were categorized as "Weak."

Results: The GAF has formulated a total of 49 recommendations and statements on the diagnosis and treatment of NOA, including 21 for diagnosis and 28 for treatment. The recommendations and statements were evaluated and graded by a panel of 48 GAF experts from 25 countries worldwide. The majority of experts (60.5%) had more than 10 years of clinical experience in managing NOA.

Conclusions: The GAF guidelines address discrepancies in NOA management across diverse clinical settings and provide comprehensive graded recommendations to guide clinicians in its diagnosis and treatment. Developed and graded by a large worldwide panel of experts, the current guidelines present simplified, high-standard strategies that can be seamlessly integrated into the daily global practice, offering practitioners a clear framework for managing NOA.

Keywords: Azoospermia; Guideline; Infertility; Pregnancy; Semen; Sperm retrieval.

Fig. 1. Algorithm for the evaluation and diagnosis of azoospermia. OA: obstructive azoospermia, NOA: non-obstructive azoospermia, CFTR: cystic fibrosis transmembrane conductance regulator, ART: assisted reproductive techniques, TRUS: transrectal ultrasonography, MRI: magnetic resonance imaging, SSR: Surgical sperm retrieval, CBAVD: congenital bilateral absence of vas deferens, EDO: ejaculatory duct obstruction; FSH: follicle stimulating hormone, LH: luteinizing hormone, T: testosterone. ^*If the biopsy shows spermatogenesis defect, continue as NOA.

Fig. 2. Treatment algorithm of NOA. NOA: non-obstructive azoospermia, LH: luteinizing hormone, FSH: follicle stimulating hormone, T: testosterone, T/E ratio: testosterone/estradiol ratio, AZF: azoospermia factor, hCG: Human chorionic gonadotropin, mTESE: microsurgical testicular sperm extraction, FNA: fine needle aspiration, ICSI: intracytoplasmic sperm injection, AI: aromatase inhibitor, SSR: surgical sperm retrieval.