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Clinical Aspects of Male Infertility and Azoospermia

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Reproductive Medicine & Andrology".

Deadline for manuscript submissions: 20 October 2026 | Viewed by 463

Editor


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Guest Editor
Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Interests: male infertility; diagnosis of male infertility; varicocele; sperm function and quality; human spermatogenesis
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Special Issue Information

Dear Colleagues,

Male infertility affects a substantial proportion of couples worldwide, and the male factor contributes to roughly half of infertility cases. Azoospermia represents a particularly challenging clinical presentation because it includes diverse and sometimes reversible etiologies, ranging from hypogonadotropic hypogonadism and ejaculatory duct obstruction to primary testicular failure. Contemporary clinical practice increasingly relies on integrated phenotyping that combines endocrine assessment, genetic testing, imaging, and refined semen and sperm function evaluation to support accurate diagnosis, counseling, and individualized management.

At the same time, important gaps remain. These include variability in diagnostic workups, limited tools to predict sperm retrieval and reproductive outcomes in non obstructive azoospermia, inconsistent reporting of clinically meaningful endpoints such as pregnancy and live birth, and uneven adoption of transparent standards for study design and outcome reporting. Addressing these gaps is essential to align research with patient priorities and to support evidence-based decision making in clinical practice.

This Special Issue of the Journal of Clinical Medicine, entitled Clinical Insights into Male Infertility and Azoospermia, aims to provide an up to date and clinically actionable forum that spans evaluation and treatment across the full spectrum of male infertility. We welcome manuscripts that bridge guideline informed care with emerging clinical tools, including advances in genetic diagnostics and counseling, biomarker development, surgical and laboratory strategies for sperm retrieval and cryopreservation, and data driven approaches to risk stratification.

We particularly encourage well designed original clinical studies, pragmatic trials, and high-quality systematic reviews and meta-analyses that address real world decision points such as diagnostic algorithms, patient counseling, selection for medical therapy, selection for sperm retrieval procedures, and reporting of outcomes in a standardized manner. We look forward to contributions that will help clinicians and researchers refine care for men with infertility and azoospermia.

Prof. Dr. Nikolaos Sofikitis
Guest Editor

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Keywords

  • azoospermia
  • non obstructive azoospermia
  • obstructive azoospermia
  • microdissection testicular sperm extraction
  • varicocele
  • hypogonadotropic hypogonadism

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Published Papers (1 paper)

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Review

33 pages, 2067 KB  
Review
Micro-TESE in Non-Obstructive Azoospermia: Phenotype-Guided Hormonal Optimization and Testosterone Response—Prognostic Biomarker or Therapeutic Target?
by Aris Kaltsas
J. Clin. Med. 2026, 15(15), 5805; https://doi.org/10.3390/jcm15155805 - 24 Jul 2026
Viewed by 221
Abstract
Non-obstructive azoospermia (NOA) is the most severe phenotype of male-factor infertility and reflects impaired spermatogenesis rather than ductal obstruction. Microdissection testicular sperm extraction (micro-TESE) is the primary sperm retrieval method, but sperm retrieval rates remain at approximately 40–60% and vary with etiology, genetics, [...] Read more.
Non-obstructive azoospermia (NOA) is the most severe phenotype of male-factor infertility and reflects impaired spermatogenesis rather than ductal obstruction. Microdissection testicular sperm extraction (micro-TESE) is the primary sperm retrieval method, but sperm retrieval rates remain at approximately 40–60% and vary with etiology, genetics, histopathology, surgical expertise, and endocrine phenotype. This narrative review synthesizes major international and regional guidelines and contemporary evidence on preoperative hormonal optimization, with particular emphasis on endogenous testosterone dynamics. Exogenous testosterone is contraindicated in fertility-seeking men because it suppresses gonadotropins and intratesticular testosterone. By contrast, selective estrogen receptor modulators, aromatase inhibitors, human chorionic gonadotropin, and follicle-stimulating hormone aim to preserve or augment endogenous Leydig- and Sertoli-cell function. Low-certainty, predominantly observational evidence suggests an association between hormonal pretreatment and higher sperm retrieval in selected normogonadotropic or hypogonadal men, but not consistently in hypergonadotropic NOA. A larger testosterone rise during stimulation has been positively associated with retrieval and may reflect residual Leydig-cell reserve, although causality and transferable thresholds remain unproven. Preoperative endocrine therapy should therefore remain individualized, phenotype-guided, off-label, closely monitored, and preferably investigated within clinical trials; the testosterone response is best regarded as a candidate prognostic biomarker rather than a validated therapeutic target or decision rule. Full article
(This article belongs to the Special Issue Clinical Aspects of Male Infertility and Azoospermia)
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