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Medicina
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Advances in the Management of Male Infertility: Innovative Strategies and...
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Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Urology & Nephrology".

Deadline for manuscript submissions: 2 June 2024 | Viewed by 10492

Special Issue Editors

Dr. Aris Kaltsas

E-Mail Website
Guest Editor
Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece
Interests: male infertility; azoospermia; varicocele; male hypogonadism
Prof. Dr. Nikolaos Sofikitis

E-Mail Website
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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce a special issue of Medicina focused on "Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment". Male infertility is a complex problem affecting millions of men worldwide. Although it is widespread, many aspects of male infertility remain poorly understood, and effective treatment options are limited. This special issue of Medicina highlights recent advances in the treatment of male infertility, focusing on innovative strategies and new technologies for improved diagnosis and treatment. We welcome original research articles, reviews, and perspectives that cover a range of topics related to male infertility, including but not limited to:

  • New diagnostic methods for male infertility, such as genetic testing and imaging
  • New technologies for the treatment of male infertility, e.g., gene therapy and stem cell therapy
  • Innovative treatment strategies for male infertility, including surgical interventions, pharmacological therapies, and assisted reproductive technologies.
  • Advances in understanding the causes of male infertility, including genetic and environmental factors
  • The role of diet and nutritional supplements in male infertility
  • The impact of male infertility on mental health and quality of life
  • Emerging technologies for male infertility management, such as genomics, proteomics, and metabolomics
  • The future of male infertility treatment, including the potential of personalized medicine and precision therapies.

We also welcome submissions on other topics related to the management of male infertility. All submissions will be subject to a rigorous peer-review process, and accepted papers will be published in a special issue of Medicina. Please submit your manuscript online through the Medicina’s submission system, indicating that your paper is intended for the special issue on "Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment". We look forward to receiving your submissions and to publishing a comprehensive overview of recent development in the management of male infertility.

Sincerely,

Dr. Aris Kaltsas
Prof. Dr. Nikolaos Sofikitis
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 100 words) can be sent to the Editorial Office for announcement on this website.

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-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly 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 1800 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
  • diagnosis
  • treatment
  • assisted reproductive technologies
  • pharmacological interventions

Published Papers (6 papers)

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Research

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14 pages, 836 KiB  
Article
Effects of the Neuropeptides Pituitary Adenylate Cyclase Activating Polypeptide and Vasoactive Intestinal Peptide in Male Fertility
by Roba Bdeir, Maha S. Al-Keilani and Khaldoun Khamaiseh
Medicina 2024, 60(4), 652; https://doi.org/10.3390/medicina60040652 - 18 Apr 2024
Viewed by 491
Abstract
Background and Objectives: The neuroendocrine system plays a crucial role in regulating various bodily functions, including reproduction, with evidence suggesting its significant involvement in male fertility and sperm development. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are expressed [...] Read more.
Background and Objectives: The neuroendocrine system plays a crucial role in regulating various bodily functions, including reproduction, with evidence suggesting its significant involvement in male fertility and sperm development. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are expressed in both male and female reproductive tissues, influencing penile erection and regulating steroidogenesis in males. Therefore, our study aimed to compare the protein levels of VIP and PACAP in seminal plasma between healthy controls and sub-fertile patients. Additionally, we sought to correlate the levels of these biomarkers with clinical, functional, and laboratory findings in the participants. Materials and Methods: The study included a total of 163 male participants for analysis. The participants were further stratified into subgroups of fertile and sub-fertile men of four subgroups according to the 2021 WHO guidelines. Seminal plasma concentrations of the neuropeptides VIP and PACAP were measured using human enzyme-linked immunosorbent assay technique. Results: The findings showed statistically significant differences in total sperm count, sperm concentration, total motility, and vitality (p < 0.001) between the fertile group and the sub-fertile group. Specifically, significant differences found between healthy males and oligoasthenospermic patients (p = 0.002), and between asthenospermic and oligoasthenospermic patients (p = 0.039). An ROC analysis showed associated sensitivity and specificity values of 62.2% and 55.6%, respectively, to PACAP seminal levels differentiated between sub-fertile patients from fertile males (p = 0.028). No significant difference in seminal levels of VIP was found between the sub-fertile and fertile groups. Conclusions: Previous research leads to the point of PACAP active involvement in spermatogenesis. In accordance to our study, in human semen samples, we have seen a significance change in PACAP levels amongst patients with low sperm count or with both low sperm count and low motility, hinting at its contribution and acting as a possible factor in this complex process. Thus, alterations in the levels or actions of these neuropeptides have been associated with certain reproductive disorders in males. Full article
(This article belongs to the Special Issue Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment)
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Review

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14 pages, 338 KiB  
Review
Impact of GLP-1 Agonists on Male Reproductive Health—A Narrative Review
by Alexandra Aponte Varnum, Edoardo Pozzi, Nicholas Allen Deebel, Aymara Evans, Nathalie Eid, Hossein Sadeghi-Nejad and Ranjith Ramasamy
Medicina 2024, 60(1), 50; https://doi.org/10.3390/medicina60010050 - 27 Dec 2023
Cited by 1 | Viewed by 3089
Abstract
Background and objective—Obesity is a prevalent health concern that notably impairs male fertility through hormonal disruptions and other pathophysiological alterations. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can significantly reduce weight. This narrative review synthesizes the existing literature discussing the impact of glucagon-like [...] Read more.
Background and objective—Obesity is a prevalent health concern that notably impairs male fertility through hormonal disruptions and other pathophysiological alterations. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can significantly reduce weight. This narrative review synthesizes the existing literature discussing the impact of glucagon-like peptide-GLP-1 RAs on the male reproductive system, particularly on the hypothalamic–pituitary–gonadal axis and spermatogenesis, highlighting their potential impact on male fertility. Material and methods—PubMed database was used for the retrieval of English-language articles published up to November 2023. This non-systematic literature review predominantly concentrates on both pre-clinical and clinical studies pertaining to GLP-1 RAs, specifically exploring their impact on male reproductive hormones and sperm parameters. Results—GLP-1 receptors have been identified within the male reproductive system according to the existing literature. While the exact mechanisms are not well understood, they appear to be involved in glucose homeostasis and energy metabolism, both vital processes in spermatogenesis. Multiple clinical trials have demonstrated the efficacy of GLP-1 RAs for promoting weight loss. Recent studies show that the use of GLP-1 RAs in obese males may enhance sperm metabolism, motility, and insulin secretion in vitro, along with positive effects on the human Sertoli cells. Recent clinical trials discussed in this review demonstrate weight loss associated with GLP-1 RAs is correlated with improvements in sperm count, concentration, and motility. However, the direct impact of GLP-1 RAs on male reproductive hormones remains unclear, necessitating further research to confirm their potential role in treating male infertility. Conclusions—This narrative review summarizes the existing literature discussing the potential impact of GLP-1 RA on the male reproductive system, emphasizing their potential therapeutic role in addressing idiopathic infertility in obese men. Despite numerous studies exploring the influence of GLP-1 and GLP-1 RAs on reproductive hormones, testicular function, and spermatogenesis, further clinical trials are crucial to validate initial evidence. Longer follow-up periods are essential to address uncertainties regarding the long-term repercussions and outcomes of GLP-1 RA use. While this holds true, the current literature suggests that GLP-1RAs show promise as a potential therapeutic approach for improving sperm parameters in obese men. Full article
(This article belongs to the Special Issue Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment)
12 pages, 449 KiB  
Review
Next-Generation Sequencing to Elucidate the Semen Microbiome in Male Reproductive Disorders
by Rhianna Davies, Suks Minhas and Channa N. Jayasena
Medicina 2024, 60(1), 25; https://doi.org/10.3390/medicina60010025 - 22 Dec 2023
Viewed by 863
Abstract
Mean sperm counts are declining at an accelerated rate and infertility is increasingly becoming a public health concern. It is now understood that human semen, previously considered to be sterile, harbours its own specific microbiome. Via activated leucocytes and the generation of reactive [...] Read more.
Mean sperm counts are declining at an accelerated rate and infertility is increasingly becoming a public health concern. It is now understood that human semen, previously considered to be sterile, harbours its own specific microbiome. Via activated leucocytes and the generation of reactive oxygen species, bacteria have the capability of evoking an immune response which may lead to sperm damage. Men with infertility have higher rates of both reactive oxygen species and sperm DNA damage. Due to the lack of sensitivity of routine culture and PCR-based methods, next-generation sequencing technology is being employed to characterise the seminal microbiome. There is a mounting body of studies that share a number of similarities but also a great range of conflicting findings. A lack of stringent decontamination procedures, small sample sizes and heterogeneity in other aspects of methodology makes it difficult to draw firm conclusions from these studies. However, various themes have emerged and evidence of highly conserved clusters of common bacteria can be seen. Depletion or over-representation of specific bacteria may be associated with aberrations in traditional and functional seminal parameters. Currently, the evidence is too limited to inform clinical practice and larger studies are needed. Full article
(This article belongs to the Special Issue Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment)
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27 pages, 1803 KiB  
Review
From Diagnosis to Treatment: Comprehensive Care by Reproductive Urologists in Assisted Reproductive Technology
by Aris Kaltsas, Fotios Dimitriadis, Dimitrios Zachariou, Athanasios Zikopoulos, Evangelos N. Symeonidis, Eleftheria Markou, Dung Mai Ba Tien, Atsushi Takenaka, Nikolaos Sofikitis and Athanasios Zachariou
Medicina 2023, 59(10), 1835; https://doi.org/10.3390/medicina59101835 - 15 Oct 2023
Viewed by 2079
Abstract
Infertility is a global health concern, with male factors playing an especially large role. Unfortunately, however, the contributions made by reproductive urologists in managing male infertility under assisted reproductive technology (ART) often go undervalued. This narrative review highlights the important role played by [...] Read more.
Infertility is a global health concern, with male factors playing an especially large role. Unfortunately, however, the contributions made by reproductive urologists in managing male infertility under assisted reproductive technology (ART) often go undervalued. This narrative review highlights the important role played by reproductive urologists in diagnosing and treating male infertility as well as any barriers they face when providing services. This manuscript presents a comprehensive review of reproductive urologists’ role in managing male infertility, outlining their expertise in diagnosing and managing male infertility as well as reversible causes and performing surgical techniques such as sperm retrieval. This manuscript investigates the barriers limiting urologist involvement such as limited availability, awareness among healthcare professionals, and financial constraints. This study highlights a decrease in male fertility due to lifestyle factors like sedentary behavior, obesity, and substance abuse. It stresses the significance of conducting an evaluation process involving both male and female partners to identify any underlying factors contributing to infertility and to identify patients who do not require any interventions beyond ART. We conclude that engaging urologists more effectively in infertility management is key to optimizing fertility outcomes among couples undergoing assisted reproductive technology treatments and requires greater education among healthcare providers regarding the role urologists and lifestyle factors that could have an effect on male fertility. Full article
(This article belongs to the Special Issue Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment)
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Other

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12 pages, 1418 KiB  
Systematic Review
Current Updates on Involvement of Artificial Intelligence and Machine Learning in Semen Analysis
by Manesh Kumar Panner Selvam, Ajaya Kumar Moharana, Saradha Baskaran, Renata Finelli, Matthew C. Hudnall and Suresh C. Sikka
Medicina 2024, 60(2), 279; https://doi.org/10.3390/medicina60020279 - 06 Feb 2024
Cited by 1 | Viewed by 1284
Abstract
Background and Objectives: Infertility rates and the number of couples undergoing reproductive care have both increased substantially during the last few decades. Semen analysis is a crucial step in both the diagnosis and the treatment of male infertility. The accuracy of semen [...] Read more.
Background and Objectives: Infertility rates and the number of couples undergoing reproductive care have both increased substantially during the last few decades. Semen analysis is a crucial step in both the diagnosis and the treatment of male infertility. The accuracy of semen analysis results remains quite poor despite years of practice and advancements. Artificial intelligence (AI) algorithms, which can analyze and synthesize large amounts of data, can address the unique challenges involved in semen analysis due to the high objectivity of current methodologies. This review addresses recent AI advancements in semen analysis. Materials and Methods: A systematic literature search was performed in the PubMed database. Non-English articles and studies not related to humans were excluded. We extracted data related to AI algorithms or models used to evaluate semen parameters from the original studies, excluding abstracts, case reports, and meeting reports. Results: Of the 306 articles identified, 225 articles were rejected in the preliminary screening. The evaluation of the full texts of the remaining 81 publications resulted in the exclusion of another 48 articles, with a final inclusion of 33 original articles in this review. Conclusions: AI and machine learning are becoming increasingly popular in biomedical applications. The examination and selection of sperm by andrologists and embryologists may benefit greatly from using these algorithms. Furthermore, when bigger and more reliable datasets become accessible for training, these algorithms may improve over time. Full article
(This article belongs to the Special Issue Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment)
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23 pages, 1559 KiB  
Systematic Review
Traditional, Complementary and Alternative Medicines in the Treatment of Ejaculatory Disorders: A Systematic Review
by Kristian Leisegang, Chinyerum Sylvia Opuwari, Faith Moichela and Renata Finelli
Medicina 2023, 59(9), 1607; https://doi.org/10.3390/medicina59091607 - 06 Sep 2023
Cited by 1 | Viewed by 1941
Abstract
Background and Objectives: Ejaculatory dysfunction (EjD) is a common male sexual disorder that includes premature ejaculation, delayed ejaculation, retrograde ejaculation, and anejaculation. Although psychological and pharmacological treatments are available, traditional, complementary, and alternative medicine (TCAM) is reportedly used. However, the clinical evidence [...] Read more.
Background and Objectives: Ejaculatory dysfunction (EjD) is a common male sexual disorder that includes premature ejaculation, delayed ejaculation, retrograde ejaculation, and anejaculation. Although psychological and pharmacological treatments are available, traditional, complementary, and alternative medicine (TCAM) is reportedly used. However, the clinical evidence for TCAM in EjD remains unclear. Therefore, this study aims to systematically review human clinical trials investigating the use of TCAM to treat EjD. Materials and Methods: A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted by searching Scopus and PubMed databases. Controlled clinical trials investigating a cohort of male patients diagnosed primarily with EjD and undergoing any TCAM intervention compared to any comparison group were included. Quality of the studies was assessed using the Cochrane Risk of Bias tool for randomized controlled trials. Results: Following article screening, 22 articles were included. Of these, 21 investigated TCAM in premature ejaculation, and only 1 investigated TCAM in retrograde ejaculation. Different TCAM categories included studies that investigated lifestyle, exercise and/or physical activities (n = 7); herbal medicine supplements (n = 5); topical herbal applications (n = 4); acupuncture or electroacupuncture (n = 3); vitamin, mineral and/or nutraceutical supplements (n = 1); hyaluronic acid penile injection (n = 1); and music therapy (n = 1). Only 31.8% (n = 7) of the included studies were found to have a low risk of bias. The available studies were widely heterogenous in the TCAM intervention investigated and comparison groups used. However, the included studies generally showed improved outcomes intra-group and when compared to placebo. Conclusions: Different TCAM interventions may have an important role particularly in the management of PE. However, more studies using standardized interventions are needed. Full article
(This article belongs to the Special Issue Advances in the Management of Male Infertility: Innovative Strategies and Emerging Technologies for Improved Diagnosis and Treatment)
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