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Advances in Male Infertility: Diagnosis, Management and ART Integration
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Advances in Male Infertility: Diagnosis, Management and ART Integration

A Special Issue of Journal of Clinical Medicine (ISSN 2077-0383) belonging to the section "Reproductive Medicine & Andrology".

Deadline for manuscript submissions: 20 January 2027 | Viewed by 2013

Editors

Dr. Despoina Mavrogianni

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Guest Editor
First Department of Obstetrics and Gynecology, Alexandra Hospital, Medical School, National and Kapodistrian University of Athens, 115 28 Athens, Greece
Interests: reproductive medicine; early pregnancy; recurrent pregnancy loss; recurrent implantation failure; gynecological ultrasound; infertility
Special Issues, Collections and Topics in MDPI journals
Dr. Sofoklis Stavros

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Guest Editor
Third Department of Obstetrics and Gynecology, University General Hospital “ATTIKON”, Athens, Greece
Interests: reproductive medicine; assisted reproduction techniques; early pregnancy; recurrent pregnancy loss; recurrent implantation failure; infertility
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, significant progress has been made in the field of male infertility, leading to improvements in diagnostic precision, therapeutic interventions, and the application of assisted reproductive technologies (ARTs). This Special Issue, entitled "Advances in Male Infertility: Diagnosis, Management and ART Integration," seeks to highlight cutting-edge research and clinical innovations that are transforming our understanding and treatment of male reproductive dysfunction.

The Special Issue will explore breakthroughs in genetic and epigenetic testing, hormonal profiling, and advanced semen analysis, offering novel insights into the identification of both overt and subclinical etiologies, including chromosomal abnormalities, Y-chromosome microdeletions, and mitochondrial dysfunction. Emphasis will be placed on the role of personalized treatment strategies, such as hormone modulation, antioxidant therapy, and surgical sperm retrieval techniques, including microdissection testicular sperm extraction (micro-TESE).

A key focus will be on the evolving integration of intracytoplasmic sperm injection (ICSI) and its impact on fertility outcomes in cases of severe male factor infertility. Additionally, the Special Issue will address emerging sperm selection and preservation techniques, including the use of microfluidics, magnetic-activated cell sorting (MACS), and cryopreservation innovations.

Importantly, this Special Issue will also welcome contributions on emerging frontiers, such as stem cell therapy, exosome-based diagnostics, and the potential of gene editing to restore spermatogenesis. By fostering a multidisciplinary perspective—bridging urology, andrology, endocrinology, genetics, and reproductive medicine—this Special Issue aims to promote a more integrated and translational approach to male infertility care.

Dr. Despoina Mavrogianni
Dr. Sofoklis Stavros
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • male infertility
  • assisted reproductive technologies (ART)
  • intracytoplasmic sperm injection (ICSI)
  • genetic testing
  • hormonal profiling
  • seminal biomarkers
  • sperm retrieval techniques
  • sperm selection
  • stem cell therapy
  • gene editing
  • reproductive endo-crinology
  • early pregnancy
  • implantation failure
  • recurrent miscarriage

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Published Papers (2 papers)

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Research

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14 pages, 1751 KB  
Article
Expression Levels of miR-99a and miR-143 in Women Diagnosed with Recurrent Pregnancy Loss
by Konstantina Kouvoutsaki, Eleni Nazou, Despoina Mavrogianni, Emmanouela Liokari, Ismini Anagnostaki, Maria Tzeli, Ioannis Arkoulis, Sofoklis Stavros, Alexandros Rodolakis, Peter Drakakis and Ekaterini Domali
J. Clin. Med. 2026, 15(15), 5955; https://doi.org/10.3390/jcm15155955 - 30 Jul 2026
Viewed by 402
Abstract
Background: Miscarriage is defined as the spontaneous loss of a pregnancy before fetal viability and includes all pregnancy losses occurring from conception until 24 weeks of gestation. Recurrent pregnancy loss (RPL) is traditionally defined as three or more consecutive miscarriages. Emerging evidence [...] Read more.
Background: Miscarriage is defined as the spontaneous loss of a pregnancy before fetal viability and includes all pregnancy losses occurring from conception until 24 weeks of gestation. Recurrent pregnancy loss (RPL) is traditionally defined as three or more consecutive miscarriages. Emerging evidence suggests that both miR-99a and miR-143 may serve as promising biomarkers for recurrent pregnancy loss. Methods: A total of 42 women of reproductive age (18–45 years) were enrolled in this study. The control group consisted of 13 women with no history of recurrent miscarriage, whereas the study group included 29 women diagnosed with spontaneous miscarriages/recurrent implantation failure. Results: Both miR-99a and miR-143 showed significantly lower relative expression in women with recurrent miscarriage/recurrent implantation failure compared with the control group. Conclusions: Despite the relatively small sample size, statistically significant differences in the expression of miR-99a and miR-143 were observed between the case and control groups, with lower relative expression of both miRNAs in the case group. These findings suggest that both microRNAs may be associated with molecular pathways involved in reproductive failure. Furthermore, investigating the expression patterns of miR-99a and miR-143 may contribute to a better understanding of the molecular mechanisms underlying recurrent miscarriage/recurrent implantation failure. Such insights may facilitate the development of genetic risk profiles for women with unexplained pregnancy loss and implantation failure, as well as support the identification of potential therapeutic targets. Further studies are required to determine their potential value as molecular markers and to clarify their functional relevance in reproductive failure. Full article
(This article belongs to the Special Issue Advances in Male Infertility: Diagnosis, Management and ART Integration)
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Review

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18 pages, 759 KB  
Review
Application of Whole-Exome Sequencing in Identifying the Molecular Basis of Idiopathic Male Infertility
by Filip Koszałka, Aleksandra Gałan, Oliwier Bułdak, Małgorzata Świąder, Jagoda Góra, Iga Kuliniec, Izabela Zakrocka, Przemysław Mitura and Wojciech Załuska
J. Clin. Med. 2026, 15(18), 7281; https://doi.org/10.3390/jcm15187281 (registering DOI) - 19 Sep 2026
Abstract
Male infertility represents a major clinical challenge. Despite standard genetic testing (karyotyping, Y-chromosome azoospermia factor (AZF) microdeletion testing, and CFTR variant analysis), the molecular cause remains unidentified in a substantial proportion of patients. These patients are consequently diagnosed with idiopathic male infertility. This [...] Read more.
Male infertility represents a major clinical challenge. Despite standard genetic testing (karyotyping, Y-chromosome azoospermia factor (AZF) microdeletion testing, and CFTR variant analysis), the molecular cause remains unidentified in a substantial proportion of patients. These patients are consequently diagnosed with idiopathic male infertility. This review provides a comprehensive overview of the current evidence regarding the application of whole-exome sequencing (WES) in the molecular diagnosis and clinical management of idiopathic male infertility. WES can identify pathogenic variants associated with quantitative spermatogenic defects, qualitative abnormalities of sperm motility and morphology, and pre-testicular causes related to hypogonadotropic hypogonadism. When defining the cohort strictly as patients with true idiopathic non-obstructive azoospermia (NOA) who remain undiagnosed after standard testing, the pooled diagnostic yield of WES is approximately 10–15%. Estimates vary due to differences in cohort selection, variant interpretation, and the range of genes analysed. Establishing a precise molecular diagnosis improves genetic counselling, helps predict the likelihood of successful sperm retrieval via testicular sperm extraction (TESE) or microdissection TESE (micro-TESE), and informs treatment planning for assisted reproductive technologies. However, routine clinical implementation remains limited by the high frequency of variants of uncertain significance, the absence of standardised diagnostic pipelines, unequal access to testing, and ethical concerns. Emerging “all-in-one” diagnostic strategies, multi-omics integration, and whole-genome or long-read sequencing hold promise for improving genomic diagnostics. However, broader adoption will ultimately require ongoing standardisation and functional validation of identified variants. Full article
(This article belongs to the Special Issue Advances in Male Infertility: Diagnosis, Management and ART Integration)
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