New Insights of Target Therapy: Effects of Tyrosine Kinase Inhibitors on Male Gonadal Function: A Systematic Review.

The number of cancer patients undergoing chronic treatment with target therapy is increasing. Although much is known about the toxicity of conventional anticancer therapies, evidence on the effects of tyrosine kinase inhibitors (TKIs) on fertility is still lacking. Therefore, this review was undertaken to evaluate the effects of TKIs on male gonadal function. A comprehensive search of PubMed and Scopus databases was conducted, focusing on the effects of TKIs on spermatogenesis and testicular endocrine function. We included animal studies, observational studies, and case reports published up to December 31, 2023. Identified articles were reviewed and analyzed to evaluate the impact of TKIs on the male gonad. Their long-term effects, the reversibility of the observed changes, and the underlying molecular mechanisms involved were recorded. The findings emerging on the effects of TKIs on male gonadal function are conflicting. Although specific TKIs (imatinib, gefitinib, sorafenib, sunitinib, quizartinib, dasatinib, and nilotinib) have been identified as potentially as potential interfering with spermatogenesis and hormone production, the extent and severity of these effects may vary from patient to patient and between different drugs within this drug class. Experimental studies on mouse models have suggested a potential interference with spermatogenesis. Evidence also suggests that TKIs affects the hypothalamic-pituitary-testicular axis, decreasing serum testosterone and gonadotropin levels. The effects of TKIs on male gonadal function highlight the need for personalized treatment choices. Potential fertility concerns can help minimize adverse effects and improve patient outcomes. Addressing the potential impact of TKIs on male fertility helps optimize cancer treatment and survival outcomes.

Antioxidants for male infertility: therapeutic scheme and indications. A retrospective single-center real-life study.

BACKGROUND: This single-center real-life study was conducted to evaluate the most effective combination of nutraceuticals and the most appropriate indications for the treatment of male infertile patients. METHODS: Infertile patients aged 20-55 years were treated with a combination of antioxidants (Androlen®; Enfarma, Misterbianco, Catania, Italy) (group A), with Androlen® (Enfarma) and a mixture of fibrinolytic molecules (Lenidase®, Enfarma) (group B), or Androlen® (Enfarma) and other molecules different from those used for the patients of the group B (group C). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection. RESULTS: Forty-three patients were enrolled. In the overall analysis, only progressive motility significantly improved after therapy. Subgroup analysis showed a significant increase in progressive motility, total motile sperm count (TMSC), and in the percentage of alive spermatozoa after treatment in the group A. Progressive motility improved significantly in patients with varicocele, while the TMSC in patients with varicocele and those with idiopathic infertility. The percentage of alive spermatozoa increased in patients with testicular hypotrophy. CONCLUSIONS: Treatment with antioxidants increased progressive sperm motility, especially in patients with varicocele or idiopathic infertility.

Artificial Intelligence in Andrology: From Semen Analysis to Image Diagnostics.

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine.

Red Wine and Sexual Function in Men: An Original Point of View.

Red wine is a rich source of nutrients whose biological properties have inspired numerous scientific studies. Indeed, it has been widely reported that there is a correlation between the positive health effects of moderate consumption of red wine and its phenolic content, which, due to its antioxidant activity, has proved to be useful in the improvement of various diseases, such as cardiovascular diseases, metabolic syndrome, cognitive disorders, depression, and cancer. It is a common opinion that the antioxidant activity of red wine is to be ascribed to its entire content of polyphenols, which act synergistically and not as a single component. Furthermore, this health-promoting effect of red wine can also be linked to its ethanol content, which has shown a wide array of biological properties. Beyond this evidence, very little is known about a possible correlation between moderate consumption of red wine and male sexual function. This brief review aimed to evaluate the effects of moderate consumption of red wine on erectile function. To accomplish this, Pubmed and Google Scholar databases were searched to retrieve the most relevant studies on this topic. The evidence so far collected has shown that red wine, if consumed in moderation, can be potentially beneficial for patients with erectile dysfunction as well as can positively influence reproductive function through mechanisms that depend on the vasorelaxant properties of red wine and its antioxidant properties.

Productivity Index in Clinical Andrology: Research Directions on High-Impact Topics and in Particular on Male Infertility.

PURPOSE: Andrological diseases have an important social and economic impact as they cause a serious impairment of the quality of life of the affected patient. Epidemiologically, the impact of these disorders is progressively increasing, as demonstrated by the ever-growing prevalence of male infertility. This evidence justifies the rapid development of research in andrology that the scientific community has undertaken in recent decades. This study aims to evaluate the productivity index of the main andrological topics studied and reported in the literature. METHODS: The total number of published articles was extracted from the Scopus database by entering the following keywords and mesh terms: "Male Infertility", "Erectile Dysfunction", "Premature Ejaculation", "Male Hypogonadism", "Testicular Tumors", "Prostate Cancer", "Prostatic hyperplasia", "Prostate hyperplasia", "Prostatitis", "Prostate inflammation", and "Male Accessory Gland Infections". Furthermore, a list of the top 50 researchers sorted by productivity was created for each topic. For male infertility, a further search was performed by combining the search term "male infertility" with the above-mentioned terms. Thus, a list of the top 30 authors in order of productivity was also extracted. The graphs were created using Excel. RESULTS AND CONCLUSIONS: As could be expected, we observed that prostate cancer and male infertility were the two most investigated topics, followed by benign prostatic hyperplasia and erectile dysfunction, whose prevalence is set to increase given the progressive aging of the population. Less investigated is the inflammation of the accessory sexual glands. In conclusion, this study provides a ranking of the main andrological topics investigated in the literature, also presenting the top list of the most productive authors for each one.

DNA Methylation in Offspring Conceived after Assisted Reproductive Techniques: A Systematic Review and Meta-Analysis.

Background: In the last 40 years, assisted reproductive techniques (ARTs) have emerged as potentially resolving procedures for couple infertility. This study aims to evaluate whether ART is associated with epigenetic dysregulation in the offspring. Methods. To accomplish this, we collected all available data on methylation patterns in offspring conceived after ART and in spontaneously conceived (SC) offspring. Results. We extracted 949 records. Of these, 50 were considered eligible; 12 were included in the quantitative synthesis. Methylation levels of H19 CCCTC-binding factor 3 (CTCF3) were significantly lower in the ART group compared to controls (SMD -0.81 (-1.53; -0.09), I2 = 89%, p = 0.03). In contrast, H19 CCCTC-binding factor 6 (CTCF6), Potassium Voltage-Gated Channel Subfamily Q Member 1 (KCNQ1OT1), Paternally-expressed gene 3 (PEG3), and Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) were not differently methylated in ART vs. SC offspring. Conclusion: The methylation pattern of the offspring conceived after ART may be different compared to spontaneous conception. Due to the lack of studies and the heterogeneity of the data, further prospective and well-sized population studies are needed to evaluate the impact of ART on the epigenome of the offspring.

Complete Androgen Insensitivity Syndrome: From the Relevance of an Accurate Genetic Diagnosis to the Challenge of Clinical Management. A Case Report.

Introduction: Androgen insensitivity syndrome (AIS), an X-linked recessive disorder of sex development (DSD), is caused by variants of the androgen receptor (AR) gene, mapping in the long arm of the X chromosome, which cause a complete loss of function of the receptor. Case presentation: We report a patient diagnosed with complete AIS (CAIS) at birth due to swelling in the bilateral inguinal region. Transabdominal ultrasound revealed the absence of the uterus and ovaries and the presence of bilateral testes in the inguinal region. The karyotype was 46,XY. She underwent bilateral orchiectomy at 9 months and was given estrogen substitutive therapy at the age of 11 years. Genetic analysis of the AR gene variants was requested when, at the age of 20, the patient came to our observation. Methods: The genetic testing was performed by next-generation sequence (NGS) analysis. Results: The genetic analysis showed the presence of the c.2242T>A, p.(Phe748Ile) variant in the AR gene. To the best of our knowledge, this variant has not been published so far. Furthermore, the patient has a heterozygous c.317A>G, p.(Gln106Arg) variation of the gonadotropin-releasing hormone receptor (GNRHR) gene, a heterozygous c.2273G>A, p.Arg758His variation of the chromodomain helicase DNA binding protein 7 (CHD7) gene, and compound heterozygous c.875A>G, p.Tyr292Cys, and c.8023A>G, p.Ile2675Val variations of the Dynein Axonemal Heavy Chain 11 (DNAH11) gene. Conclusions: The case herein reported underlines the importance of an accurate genetic analysis that has to include karyotype and AR gene variant analysis. This is useful to confirm a clinical diagnosis and establish the proper management of patients with CAIS. Numerous variants of the AR gene have not yet been identified. Moreover, several pitfalls are still present in the management of these patients. More studies are needed to answer unresolved questions, and common protocols are required for the clinical follow-up of patients with CAIS.

The penile duplex ultrasound: How and when to perform it?

BACKGROUND: Because it is a superficial structure, the penis is ideally suited to ultrasound imaging. A number of disease processes, including Peyronie's disease, penile fractures and tumors, are clearly visualized with ultrasound. Baseline and dynamic assessment of cavernosal arterial changes after pharmaco-stimulation with alprostadil allows standardized diagnosis of arterial and venogenic causes of erectile dysfunction (ED). OBJECTIVE: To illustrate how to correctly perform flaccid and dynamic penile duplex ultrasound (D-PDU) and in which patients to recommend it. MATERIALS/METHODS: An extensive search of the literature was carried out on Pubmed with the insertion of the following Medical Subjects Headings (MeSH) terms and keywords "penile color Doppler ultrasound" "peak systolic velocity" "end-diastolic velocity", "acceleration time", "resistance index". EVIDENCE: In our experience, arterial erectile dysfunction is identified after standardized intracavernous injection (ICI) of alprostadil (10 mcg) when values of peak systolic velocity (PSV) are <35 cm/s and, in the most severe forms, for values <25 cm/s. Arterial insufficiency can also be identified by increased acceleration time (AT) values (>110 ms) and/or by a lack of visualization of helicine arteries at power Doppler mode along with incomplete achievement of penile rigidity. The veno-occlusive incompetence is determined when end-diastolic velocity (EDV) values are >4.5-5 cm/s or in the case of resistance index (RI) values <0.75. The assessment of additional surrogate markers of endothelial dysfunction, that is, intima-media thickness, mean platelet volume (MPV), endothelial progenitor cells (EPC), endothelial cell specific molecule-1(endocan) are also useful in assessing the patient's cardiovascular risk but are still considered investigational in the interpretation of D-PDU results. CONCLUSION: D-PDU scan after ICI with vasoactive drugs is a safe procedure and represents the gold standard for the diagnostics of penile pathologies and should be performed in men with ED not responding to oral conventional therapies and/or in those requiring accurate stratification of cardiovascular risk.

The Role of Resveratrol in Human Male Fertility.

Resveratrol (RSV) (3,4',5 trihydroxystilbene) is a natural non-flavonoid polyphenol widely present in the Mediterranean diet. In particular, RSV is found in grapes, peanuts, berries, and red wine. Many beneficial effects of this molecule on human health have been reported. In fact, it improves some clinical aspects of various diseases, such as obesity, tumors, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, and diabetes mellitus. However, little is known about the relationship between this compound and male fertility and the few available results are often controversial. Therefore, this review evaluated the effects of RSV on human male fertility and the mechanisms through which this polyphenol could act on human spermatozoa.

Seminal Plasma Proteomic Biomarkers of Oxidative Stress.

The prevalence of idiopathic male infertility is high, up to 75% of patients with abnormal sperm parameters. Hence, the research of its causes is mandatory. Oxidative stress (OS) can be responsible for male infertility in 30-80% of cases. In recent years, seminal plasma (SP) proteomics has developed as a useful tool to provide biomarkers of specific diseases. This systematic review aims to collect the available evidence on the changes of SP proteome in patients exposed to OS to provide possible SP biomarkers of sperm OS. To accomplish this, the following keyterms "seminal fluid proteome", "seminal plasma proteome", "oxidative stress", and "sperm oxidative stress" were used and 137 records were found. Among these, 17 were finally included. Nine proteins involved with OS were found overexpressed in patients with OS. Twenty-three proteins were found differentially expressed in patients with clinical conditions associated with OS, such as varicocele, male accessory gland infection/inflammation, cigarette smoke, and obesity. These proteins do not seem to overlap among the clinical conditions taken into account. We speculate that specific SP proteins may mediate OS in different clinical conditions. Altogether, these results suggest that proteomics could help to better understand some of the molecular mechanisms involved in the pathogenesis of infertility. However, further studies are needed to identify potential biomarkers of male infertility with valuable clinical significance.