Search Results (39)

Background: Wolfram syndrome (WFS), also known as DIDMOAD, is a rare monogenic neurodegenerative disorder characterized by four key components: non-autoimmune insulin-dependent diabetes mellitus (DM), optic atrophy, sensorineural hearing loss, and diabetes insipidus. Although it significantly affects quality of life, gonadal dysfunction, particularly hypogonadism, remains underrecognized. Methods: In total, 45 patients (25 men, 20 women) with genetically confirmed WFS from a single tertiary-care center were prospectively followed to assess gonadal function. Men underwent hormonal evaluations, semen analysis, imaging tests, and testicular biopsies. In women, data on age at menarche, menstrual irregularities, and age at menopause were recorded. Hormonal analyses, including anti-Müllerian hormone (AMH) levels, and imaging tests were also conducted. Results: Hypogonadism was identified in 19 men (76.0%), of whom 17 (68.0%) had hypergonadotropic hypogonadism and 2 (8.0%) had hypogonadotropic hypogonadism. Testicular biopsies showed seminiferous tubule damage, Sertoli cell predominance, and reduced Leydig cells. Azoospermia was observed in 12 patients, whereas others presented with oligozoospermia, teratozoospermia, or asthenozoospermia. Most patients exhibited low testosterone levels along with elevated LH and FSH, suggesting primary testicular failure, except for two cases of hypogonadotropic hypogonadism. Correlations between biomarkers, onset age and severity have been analyzed and provide important insights regarding medical treatment. In women, menstrual irregularities were universal, with 20% experiencing premature menopause. Four patients had low AMH levels, with ovarian atrophy in three and a postmenopausal uterus in two, indicating early hypogonadism risk. Conclusions: Gonadal dysfunction is a significant yet overlooked feature of WFS, requiring systematic evaluation during puberty and beyond. Proper management is essential to mitigate metabolic disturbances and psychological impacts, including infertility distress, relationship challenges, and quality of life concerns. Addressing sexual health is crucial as WFS patients live longer and aspire to establish relationships or start families. Full article

Background: Sperm morphology is a key factor influencing fertilization and embryo development in assisted reproductive technology (ART). However, the predictive value of sperm deformity indices and selection techniques remains debated. This study evaluated the impact of teratozoospermia on fertilization, blastocyst formation, and embryo quality, comparing conventional and microfluidic sperm selection methods. Methods: A retrospective analysis was conducted on ART cycles involving patients with teratozoospermia. Sperm selection was performed using density gradient centrifugation (DGC) or microfluidic sperm sorting (MFSS). The correlations between the Sperm Deformity Index (SDI), Multiple Anomalies Index (MAI), and Teratozoopermia Index (TZI) with fertilization rates, blastocyst formation, and embryo quality were assessed. Statistical analysis included correlation tests, receiver operating characteristic (ROC) curves, and independent samples t-tests. Results: Patients with severe teratozoospermia exhibited lower fertilization rates (p < 0.01) and reduced blastocyst formation (p = 0.02). The SDI and MAI showed moderate negative correlations with fertilization (r = −0.15 and r = −0.25, respectively) and blastocyst development (r = −0.20 and r = −0.30, respectively), while the TZI had only weak associations (r = −0.10 and r = −0.15, respectively). ROC analysis demonstrated that the SDI and MAI were moderate predictors of embryo viability (AUC = 0.70 and 0.75, respectively). Patients who underwent microfluidic sperm selection had higher fertilization rates (p = 0.03) and improved blastocyst quality (p = 0.04) than those processed with DGC. Conclusions: Severe teratozoospermia negatively affects fertilization and blastocyst formation, with the SDI and MAI showing moderate predictive value for embryo development. The use of microfluidic sperm selection significantly improved embryo quality, supporting its clinical relevance in ART. Full article

Background/Objectives: Male infertility is becoming a serious problem affecting about 7% of all men worldwide and is a major or contributory factor in 50% of infertile couples overall. Men with abnormal semen parameters have a significantly increased risk of aneuploidy, presenting a serious concern in programmes of assisted reproductive technologies. Recently, the introduction of preimplantation genetic testing for aneuploidies (PGT-A) has increased the pregnancy rate and live births. We investigated the effect of PGT-A on the success of IVF treatment in couples with the male factor of infertility. Methods: Two experimental groups and one control group were studied: Group A (110 couples)—male partners with abnormal semen parameters, with PGT-A; Group B (110 couples)—male partners with abnormal semen parameters, without PGT-A; and Group C (105 couples)—control, male partners with normal spermograms, with PGT-A. A Day 3 blastomere biopsy was followed by FISH-based PGT-A. A total of 880 embryos from Group A and 890 embryos from Group C was analysed. Results: In patients with abnormal semen parameters, embryonic aneuploidy was twice as common compared to the control (13.6% vs. 5.8%, p < 0.001). Group B had the lowest clinical pregnancy rate (28.2%), with two out of three pregnancies ending in a miscarriage. Only 10% of IVF cycles in this group resulted in live birth compared with 35.5% for Group A and 49.5% for Group C. Conclusions: Our data demonstrate that PGT-A screening as part of IVF treatment drastically increases the clinical pregnancy rate and chances of live birth in couples where male partners have semen abnormality. Full article

Zinc plays a crucial role in spermatogenesis, sperm function, and fertilisation. Zinc homeostasis is regulated by ZIP and ZnT transporter proteins, which mediate Zn²⁺ influx and efflux across sperm cell membranes. This study analysed total Zn concentration in seminal plasma and serum of 10 normozoospermic and 32 teratozoospermic men involved in the process of infertility treatment, using inductively coupled plasma mass spectrometry. In addition, the expression of Zn transporters ZIP6 and ZIP14 in the sperm of two normozoospermic and two teratozoospermic men was analysed using immunofluorescence. Applying Student’s t test and the Mann–Whitney U test, we found no significant differences in Zn concentrations in seminal plasma and serum between groups. ZIP6 was mainly localised in the sperm head, with slightly higher immunopositivity in normozoospermic than teratozoospermic samples, but there was no statistically significant difference between the groups. ZIP14 was mainly found in the sperm head, and some teratozoospermic samples showed immunopositivity in the tail, although there were no significant differences in ZIP14 immunopositivity between normozoospermic and teratozoospermic samples. The results suggest that Zn concentrations in seminal plasma and serum, and the expression of ZIP6 and ZIP14, do not differ in normo- and teratozospermic samples, and emphasise the complex interplay of factors underlying male fertility. Full article

Objectives: Semen analysis is universally regarded as the gold standard for diagnosing male infertility, while ultrasonography plays a vital role as a complementary diagnostic tool. This study aims to assess the effectiveness of artificial intelligence (AI)-driven deep learning algorithms in predicting semen analysis parameters based on testicular ultrasonography images. Materials and Methods: This study included male patients aged 18–54 who sought evaluation for infertility at the Urology Outpatient Clinic of our hospital between February 2022 and April 2023. All patients underwent comprehensive assessments, including blood hormone profiling, semen analysis, and scrotal ultrasonography, with each procedure being performed by the same operator. Longitudinal-axis images of both testes were obtained and subsequently segmented. Based on the semen analysis results, the patients were categorized into groups according to sperm concentration, progressive motility, and morphology. Following the initial classification, each semen parameter was further subdivided into “low” and “normal” categories. The testicular images from both the right and left sides of all patients were organized into corresponding folders based on their associated laboratory parameters. Three distinct datasets were created from the segmented images, which were then augmented. The datasets were randomly partitioned into an 80% training set and a 20% test set. Finally, the images were classified using the VGG-16 deep learning architecture. Results: The area under the curve (AUC) values for the classification of sperm concentration (oligospermia versus normal), progressive motility (asthenozoospermia versus normal), and morphology (teratozoospermia versus normal) were 0.76, 0.89, and 0.86, respectively. Conclusions: In our study, we successfully predicted semen analysis parameters using data derived from testicular ultrasonography images through deep learning algorithms, representing an innovative application of artificial intelligence. Given the limited published research in this area, our study makes a significant contribution to the field and provides a foundation for future validation studies. Full article

Background/Objectives: Male infertility is a complex condition with various underlying genetic factors. microRNAs (miRNAs) play a crucial role in gene regulation, and their disruption can significantly impact fertility. This study aimed to identify variants within miRNA genes and elucidate their impact on male infertility. Methods: Whole genome sequencing was performed on blood samples from men with asthenozoospermia, oligozoospermia, and teratozoospermia, compared to normozoospermic controls. The analysis revealed a significant number of unique variants in each infertile group. We subsequently focused on variants in miRNA regions, followed by an in silico analysis to investigate the role of the identified variants and miRNAs in male infertility. Results: Focused analysis on miRNA genes identified 19 exclusive variants in teratozoospermic men, 24 in asthenozoospermic, and 27 in oligozoospermic, all mapping to pre-miRNAs or mature miRNAs. Functional analyses using Gene Ontology (GO) and KEGG pathways highlighted key biological processes and pathways disrupted by these variants and miRNA–mRNA interactions, including transcription regulation, signaling, and cancer-related pathways. Furthermore, six variants (rs17797090, rs1844035, rs7210937, rs451887, rs12233076, and rs6787734) were common across the infertile groups, suggesting their importance in male infertility or their potential as biomarkers. Common variants were also validated in another clinically relevant group of men. Some miRNAs with identified variants, such as hsa-miR-449b and hsa-miR-296, have been previously implicated in male infertility and exhibit differential expression between fertile and infertile men, according to the literature, too. Conclusion: These results provide new insights into the genetic basis of male infertility and open avenues for future research and therapeutic interventions. Full article

Infertility represents a significant global health challenge impacting millions of couples worldwide. Approximately half of all infertile couples exhibit compromised semen quality, indicative of diminished male fertility. While the diagnosis of male infertility traditionally relies on semen analysis, its limitations in providing a comprehensive assessment of male reproductive health have spurred efforts to identify novel biomarkers. Seminal plasma, a complex fluid containing proteins, lipids, and metabolites, has emerged as a rich source of such indicators. Reproduction depends heavily on seminal plasma, the primary transporter of chemicals from male reproductive glands. It provides a non-invasive sample for urogenital diagnostics and has demonstrated potential in the identification of biomarkers linked to illnesses of the male reproductive system. The abundance of seminal proteins has enabled a deeper understanding of their biological functions, origins, and differential expression in various conditions associated with male infertility, including azoospermia, asthenozoospermia, oligozoospermia, teratozoospermia, among others. The true prevalence of male infertility is understated due to the limitations of the current diagnostic techniques. This review critically evaluates the current landscape of seminal plasma biomarkers and their utility in assessing male infertility. Βy bridging the gap between research and clinical practice, the integrative assessment of seminal plasma biomarkers offers a multimodal approach to comprehensively evaluate male infertility. Full article

Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed. Full article

Background: The impact of sexual abstinence on sperm quality, particularly in pathological cases, is a subject of debate. We investigated the link between abstinence duration and semen quality in both normal and pathological samples. Methods: We analyzed semen samples from 4423 men undergoing fertility evaluation, comprising 1256 samples from healthy individuals and 3167 from those with conditions such as oligozoospermia, asthenozoospermia, teratozoospermia, or a combination of these factors, namely oligoasthenoteratozoospermia (OAT). Parameters including sperm concentration, the percentage of progressively motile spermatozoa, total motile sperm count, and the percentage of spermatozoa with normal morphology were assessed at various abstinence durations (each day, 0–2, 3–7, and >7 days). Results: Extended abstinence correlated with higher sperm concentration overall (p < 0.001), except in oligozoospermia. Longer abstinence reduced progressive motility in normal (p < 0.001) and teratozoospermic samples (p < 0.001). Shorter abstinence was linked to higher morphologically normal sperm in normal samples (p = 0.03), while longer abstinence did so in oligoasthenoteratozoospermic samples (p = 0.013). Conclusion: The findings suggest that a prolonged abstinence time is linked to higher sperm concentration, while optimal sperm motility is observed after shorter abstinence periods. However, results regarding morphology remain inconclusive. Recommendations on abstinence duration should be tailored based on the specific parameter requiring the most significant improvement. Full article

Teratozoospermia, a complex male fertility disorder affecting sperm morphology, has been linked to AURKC, SPATA16, and SUN5 gene defects. However, the sheer volume of SNPs in these genes necessitates prioritization for comprehensive analysis. This study focuses on the often-overlooked untranslated region (UTR) variants in these genes, aiming to assess their association with teratozoospermia and prioritize them. We employed a multi-step filtering process, including functional significance assessment (RegulomeDB, 3DSNP v2.0, SNPinfo (FuncPred)), evaluation of gene expression impacts in testis tissue using GTEx, and assessment of miRNA binding site effects (PolymiRTS Database 3.0, miRNASNP v3). Additionally, we used SNPnexus to evaluate their conservation and association with diseases. In AURKC, we identified six UTR SNPs (rs11084490, rs58264281, rs35582299, rs533889458, rs2361127, rs55710619), two of which influenced gene expression in testis, while others affected the binding sites of 29 miRNAs or were located in transcription-factor binding sites. Three of these SNPs were also found to be associated with spermatogenic failure according to previous studies indicating a potential regulatory role in teratozoospermia, too. For SPATA16, two 3′ UTR variants, rs146640459 and rs148085657, were prioritized, with the latter impacting miRNA binding sites. In SUN5, three 3′ UTR variants (rs1485087675, rs762026146, rs1478197315) affected miRNA binding sites. It should be noted that none of the above variants was identified in a conserved region. Our findings shed light on the potential regulatory roles of these SNPs in teratozoospermia and lay the foundation for future research directions in this area. Full article

Male infertility is a global health issue, affecting over 20 million men worldwide. Genetic factors are crucial in various male infertility forms, including teratozoospermia. Nonetheless, the genetic causes of male infertility remain largely unexplored. In this study, we employed whole-genome sequencing and RNA expression analysis to detect differentially expressed (DE) long-noncoding RNAs (lncRNAs) in teratozoospermia, along with mutations that are exclusive to teratozoospermic individuals within these DE lncRNAs regions. Bioinformatic tools were used to assess variants’ impact on lncRNA structure, function, and lncRNA–miRNA interactions. Our analysis identified 1166 unique mutations in teratozoospermic men within DE lncRNAs, distinguishing them from normozoospermic men. Among these, 64 variants in 23 lncRNAs showed potential regulatory roles, 7 variants affected 4 lncRNA structures, while 37 variants in 17 lncRNAs caused miRNA target loss or gain. Pathway Enrichment and Gene Ontology analyses of the genes targeted by the affected miRNAs revealed dysregulated pathways in teratozoospermia and a link between male infertility and cancer. This study lists novel variants and lncRNAs associated for the first time with teratozoospermia. These findings pave the way for future studies aiming to enhance diagnosis and therapy in the field of male infertility. Full article

(1) Background: While females start their gynecological examinations during puberty, only few men decide to be visited by urologists in their youth. Given the participation in the EcoFoodFertility research project, our department had the opportunity to screen young males that were supposedly healthy. (2) Results: from January 2019 to July 2020, we evaluated 157 patients with sperm, blood analysis, and uroandrological examinations. The inclusion criteria were age 18–40 and absence of previous urological disease (urology-naïve). The primary endpoint of the study was to record uroandrological diseases that are occasionally discovered during examination in asymptomatic young men. The average age was 26.9 years (range 18–40); average testicular volume was 15.7 mL (range 12–22 mL); and 45.2% reported abnormal semen analysis: 62 cases of teratozoospermia, 27 asthenozoospermia, 18 oligozoospermia, and 2 azoospermia were discovered respectively; 4/157 patients were diagnosed with hypogonadism; 2 cases with suspicious testicular mass resulted in testicular cancer; and 31 suspected varicoceles and 8 patients with mild sexual dysfunctions were managed. (3) Conclusions: an uroandrological evaluation of young asymptomatic males allowed for the prompt diagnosis of different urological conditions, including cancerous ones, in our series. Despite being debatable, combining urological counselling with physical examination, semen analysis, and a laboratory profile could be useful and cost-effective in order to ameliorate male health. Full article

Chromosomal polymorphisms are structural variations in chromosomes that define the genomic variance of a species. These alterations are recurrent in the general population, and some of them appear to be more recurrent in the infertile population. Human chromosome 9 is highly heteromorphic, and how its rearrangement affects male fertility remains to be fully investigated. In this study, we aimed to investigate the association between the polymorphic rearrangements of chromosome 9 and male infertility via an Italian cohort of male infertile patients. Cytogenetic analysis was carried out, along with Y microdeletion screening, semen analysis, fluorescence in situ hybridization, and TUNEL assays using spermatic cells. Chromosome 9 rearrangements were observed in six patients: three of them showed a pericentric inversion, while the others showed a polymorphic heterochromatin variant 9qh. Of these, four patients exhibited oligozoospermia associated with teratozoospermia, along with a percentage of aneuploidy in the sperm of above 9%, in particular, an increase in XY disomy. Additionally, high values for sperm DNA fragmentation (≥30%) were observed in two patients. None of them had microdeletions to the AZF loci on chromosome Y. Our results suggest that polymorphic rearrangements of chromosome 9 might be associated with abnormalities in sperm quality due to incorrect spermatogenesis regulation. Full article

Sperm separation plays a critical role in assisted reproductive technology. Based on migration, density gradient centrifugation and filtration, a properly selected sperm could help in increasing assisted reproductive outcomes in teratozoospermia (TZs). The current study aimed to assess the prognostic value of four sperm selection techniques: density gradient centrifugation (DGC), swim-up (SU), DGC-SU and DGC followed by magnetic-activated cell sorting (DGC-MACS). These were evaluated using spermatozoa functional parameters. A total of 385 infertile couples underwent the procedure of intracytoplasmic sperm injection (ICSI), with an isolated teratozoospermia in the male partner. Semen samples were prepared by using one of the mentioned sperm preparation techniques. The improvements in the percentage of normal mature spermatozoa, rate of fertilization, cleavage, pregnancy and the number of live births were assessed. The normal morphology, spermatozoa DNA fragmentation (SDF) and chromatin maturity checked by using chromomycin A3 (CMA3) with DGC-MACS preparation were better compared to the other three methods. Embryo cleavage, clinical pregnancy and implantation were better improved in the DGC-MACS than in the other tested techniques. The DGC-MACS technique helped in the selection of an increased percentage of normal viable and mature sperm with intact chromatin integrity in patients with teratozoospermia. Full article

Male infertility is a common and complex disease and presents as a wide range of heterogeneous phenotypes. Multiple morphological abnormalities of the sperm flagellum (MMAF) phenotype is a peculiar condition of extreme morphological sperm defects characterized by a mosaic of sperm flagellum defects to a total asthenozoospermia. At this time, about 40 genes were associated with the MMAF phenotype. However, mutation prevalence for most genes remains individually low and about half of individuals remain without diagnosis, encouraging us to pursue the effort to identify new mutations and genes. In the present study, an a cohort of 167 MMAF patients was analyzed using whole-exome sequencing, and we identified three unrelated patients with new pathogenic mutations in DNHD1, a new gene recently associated with MMAF. Immunofluorescence experiments showed that DNHD1 was totally absent from sperm cells from DNHD1 patients, supporting the deleterious effect of the identified mutations. Transmission electron microscopy reveals severe flagellum abnormalities of sperm cells from one mutated patient, which appeared completely disorganized with the absence of the central pair and midpiece defects with a shortened and misshapen mitochondrial sheath. Immunostaining of IFT20 was not altered in mutated patients, suggesting that IFT may be not affected by DNHD1 mutations. Our data confirmed the importance of DNHD1 for the function and structural integrity of the sperm flagellum. Overall, this study definitively consolidated its involvement in MMAF phenotype on a second independent cohort and enriched the mutational spectrum of the DNHD1 gene. Full article