Y Chromosome and Male Fertility: The AZF Genes and Their Deletion

AZFc deletions yield sperm retrieval in 58.85% of azoospermic men; complete AZFa/b deletions are essentially futile for TESE.

Journal: Annales d'endocrinologie | Published: 2026-05-07 | Type: Review | PMID: 42103583 Authors: Krausz Csilla, Abrardo Chiara, Bonini Viola (University of Florence); Vargha Judit, Kopa Zsolt (Semmelweis University, Budapest) Funding/COI: Funding not listed; authors declare no competing interests

Summary

The Y chromosome's long arm harbors three AZoospermia Factor (AZF) regions — a, b, and c — whose deletions are the most common known genetic cause of impaired sperm production. This review from two established andrology centers synthesizes the literature on testicular sperm extraction (TESE) outcomes by deletion type and adds the authors' own data. The headline number: men with complete AZFc deletions had sperm retrieved 58.85% of the time, making TESE a reasonable option; men with complete AZFa or AZFb deletions had essentially zero viable TESE outcomes, while partial deletions in those regions are a messier, phenotype-variable story.

Claims

• Complete AZFc deletion: 58.85% overall TESE success rate (pooled from literature + authors' data); men may have severely reduced sperm counts or azoospermia but retain some spermatogenic potential
• Complete AZFa deletion: near-zero TESE success; associated with Sertoli-cell-only syndrome
• Complete AZFb deletion: near-zero TESE success; associated with spermatogenic arrest
• Partial AZFa and AZFb deletions: semen and testicular phenotypes "vary considerably" — some partial deletions leave fertility intact, others do not; accurate deletion mapping is essential before counseling patients
• AZF screening is currently the only available pre-TESE predictive test — no other genetic or hormonal marker reliably forecasts sperm retrieval success in azoospermic men with Y deletions
• Genetic counseling implications: sons of men who father children via TESE will inherit the deletion and likely face the same fertility challenges

Study Quality

This is a narrative/structured review, not a systematic review or meta-analysis, which limits its evidentiary weight. The 58.85% figure is a pooled summary across multiple studies plus the authors' own institutional data, but the review does not report the total N contributing to that figure, nor does it appear to weight studies by quality or account for heterogeneity in TESE protocols across centers. That's a meaningful gap — TESE success rates vary substantially by surgical technique, surgeon experience, and patient selection, none of which are controlled for here.

The authors are from two recognized andrology centers (Florence and Semmelweis), and Krausz Csilla is one of the most cited researchers in Y chromosome genetics, lending credibility to the clinical interpretation. However, including "original data" without a clear description of that dataset's size, design, or selection criteria in the abstract raises questions about how much the authors' own results are driving the pooled figure.

Red Flags

• No systematic search strategy described — this is a narrative review, subject to selection bias in which studies the authors chose to include
• The 58.85% TESE success rate lacks a reported denominator (total N) in the abstract; readers cannot assess whether this pools 50 patients or 5,000
• "Original data" contribution is opaque — unclear how it was integrated or what weight it carries
• Funding not listed; while COI is declared clean, absence of funding disclosure is a minor transparency gap
• Partial AZFa/b deletions are described as variable without providing a quantitative breakdown of outcomes — this is the clinically murkiest category and gets the least rigorous treatment

Strengths

• Clinically actionable framework: clear stratification of complete vs. partial deletions with direct implications for TESE counseling
• Addresses a genuine gap — most patients and many clinicians conflate all Y microdeletions as equivalent; this review correctly disaggregates them
• Integrates genetic counseling implications, including the hereditary transmission risk to male offspring
• Authors have substantial domain expertise in Y chromosome genetics

Verdict

This review is a useful clinical reference for stratifying TESE candidacy in azoospermic men by AZF deletion type, and the 58.85% AZFc TESE success rate is a concrete, citable figure. But it's a narrative review, not a meta-analysis, so treat it as an expert synthesis rather than definitive evidence. The partial AZFa/b section — arguably the most clinically vexing category — gets the thinnest quantitative treatment. Worth reading for the AZFc data and the genetic counseling framework; don't cite it as if it were a pooled systematic analysis.