Search Results (89)

Male infertility is a multifactorial condition often associated with disruptions in sperm metabolism and mitochondrial function, yet traditional semen analysis provides limited insight into these molecular mechanisms. Understanding sperm bioenergetics and metabolic dysfunctions is crucial for improving the diagnosis and treatment of conditions such as asthenozoospermia and azoospermia. This systematic review synthesizes recent literature, focusing on advanced tools and techniques—including omics technologies, advanced imaging, spectroscopy, and functional assays—that enable comprehensive molecular assessment of sperm metabolism and development. The reviewed studies highlight the effectiveness of metabolomics, proteomics, and transcriptomics in identifying metabolic biomarkers linked to male infertility. Non-invasive imaging modalities such as Raman and magnetic resonance spectroscopy offer real-time metabolic profiling, while the seminal microbiome is increasingly recognized for its role in modulating sperm metabolic health. Despite these advances, challenges remain in clinical validation and implementation of these techniques in routine infertility diagnostics. Integrating molecular metabolic assessments with conventional semen analysis promises enhanced diagnostic precision and personalized therapeutic approaches, ultimately improving reproductive outcomes. Continued research is needed to standardize biomarkers and validate clinical utility. Furthermore, these metabolic tools hold significant potential to elucidate the underlying causes of previously misunderstood and unexplained infertility cases, offering new avenues for diagnosis and treatment. Full article

Background/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive a first child) and secondary male infertility (which occurs when a man who has already fathered a child faces difficulty conceiving again) remain poorly understood at the genetic level. This study explored the role of single-nucleotide polymorphisms (SNPs) in mitochondrial genes (MT-ND3, MT-ND4L, and MT-ND4) in primary and secondary male infertility. Methods: This study analyzed the genotype distributions of SNPs in 68 infertile males (49 with primary infertility and 19 with secondary infertility) using Sanger sequencing. Results: Key findings revealed that studied SNPs were significantly associated with infertility type. Specifically, rs2857285 (T>C,G) in the ND4 gene showed a significant correlation (p = 0.023) with the TT genotype, which is prominent in primary infertility. Another SNP, rs28358279 (T>A,C) in the ND4L gene, also demonstrated a significant correlation (p = 0.046) with the TT genotype, being more common in primary infertility. In addition, rs869096886 (A>G) in the ND4 gene had a borderline correlation (p = 0.051), indicating a possible association between this SNP and reproductive duration. Conclusions: This study emphasizes the potential relevance of mitochondrial malfunction in male infertility, specifically the effects of studied SNPs on sperm survival and function over time. These findings suggest that certain mitochondrial SNPs might be potential biomarkers for infertility risk. Larger studies are needed to confirm these associations and examine the functional effects of these SNPs. Combining genetic analysis with environmental and lifestyle factors could enhance our understanding of male infertility and improve diagnostic and therapeutic strategies. Full article

The epigenetic landscape plays a pivotal role in regulating the functions of both germ and somatic cells (Sertoli and Leydig cells) within the testis, which are essential for male fertility. While somatic cells support germ cell maturation and testosterone synthesis, the epigenetic regulation of germ cells is critical for proper spermatogenesis and function. Epigenetic modifications such as DNA methylation, histone modifications, chromatin remodeling, and non-coding RNAs (ncRNAs) are crucial for regulating gene expression that is essential for spermatogenesis and reproductive function. Although numerous studies have highlighted the significance of the epigenome and its implications for male reproductive health, a comprehensive overview of the existing literature and knowledge is lacking. This review aims to provide an in-depth analysis of the role of epigenetics in spermatogenesis and reproductive health, with a specific focus on DNA methylation, histone remodeling, and small noncoding RNAs (sncRNAs). Additionally, we examine the impact of lifestyle and environmental factors, such as diet, smoking, physical activity, and exposure to endocrine-disrupting chemicals, on the sperm epigenome. We emphasize how these factors influence fertility, embryonic development, and potential transgenerational inheritance. This review underscores how recent advances in the understanding of the epigenetic modulation of testicular function can inform the pathophysiology of male infertility, thereby paving the way for the development of targeted diagnostic and therapeutic strategies. Full article

Infertility is a complex and common problem in reproductive medicine consultations. Three factors must be examined during the preconception phase: breeding management, the fertility of the bitch, and the fertility of the stud dog. Among these factors, improper breeding management remains the main cause of reproductive failure, with accurate recognition of ovulation being crucial for successful mating. Artificial insemination allows for a thorough evaluation of semen quality compared to natural mating. In addition, genetic selection, nutritional factors, and reproductive health management can either impair or improve the fertility of females and males. Idiopathic infertility can occur in bitches, but it is important to rule out other possible causes first. In bitches with irregular estrus cycles, ovarian dysfunction and endocrine imbalances should be investigated. In bitches with regular cycles, uterine disorders such as cystic endometrial hyperplasia, endometritis or congenital anomalies may be the cause. Both mating-related and chronic endometritis are recognized as contributing factors to infertility. Infectious agents, particularly Brucella spp. and Mycoplasma spp., should also be evaluated, although interpretation of Mycoplasma test results requires caution. In males presenting with poor semen quality, potential causes include infectious diseases (with brucellosis always requiring exclusion), hormonal imbalances, and the impact of exogenous treatments. The article underscores the critical role of comprehensive diagnostic protocols, proactive health surveillance, and data-driven breeding strategies in systematically addressing this multifaceted challenge. Full article

Standard semen parameters remain the cornerstone of male infertility evaluation, though they often poorly reflect the likelihood of success in assisted reproductive technology (ART). This study evaluates sperm DNA fragmentation (SDF) as a diagnostic tool for male infertility and predictive biomarker for ART success. Semen samples were collected from 20 fertile donors and 40 infertile patients with abnormal semen parameters. A fraction of each sample was used for SDF assessment via TUNEL assay and flow cytometry, while the remaining portion was processed for conventional semen analysis and ART. Infertile patients exhibited higher SDF levels (32.77 ± 13.61%) compared to donors (22.19 ± 8.37%; p < 0.01), a difference that remained statistically significant across all subgroups stratified by semen parameters. Additionally, significant correlations were obtained between the percentage of SDF and sperm count (r = −0.4036), motility (r = −0.6377), and morphology (r = −0.2783). Regarding ART outcomes, patients with low-quality embryos exhibited higher SDF levels compared to those with high-quality embryos (30.02 ± 12.52% vs. 23.16 ± 8.41%; p = 0.0036). Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUC) above 0.7 for the classification of male infertility as well as the assessment of embryo quality. Overall, our results support the utility of SDF as both a diagnostic biomarker for male infertility and a predictive indicator of embryo quality in ART, particularly in the presence of an oocyte-related female factor. Full article

Male infertility is an under-recognized global health burden. Accumulating evidence position the intestinal microbiota as a pivotal regulator of testicular function, underpinning the emerging gut microbiota–testis axis. This narrative review introduces the conceptual term “androbactome”, referring to gut microorganisms and microbial genes that are hypothesized to influence androgen biosynthesis, spermatogenesis, and broader reproductive endocrinology. The documented worldwide decline in sperm concentration heightens the urgency of clarifying microbe-mediated influences on male reproductive capacity. The synthesis of preclinical and clinical findings reveals four principal pathways by which dysbiosis compromises fertility: systemic inflammation, oxidative stress, endocrine disruption, and epigenetic alteration. Lipopolysaccharide-driven cytokinaemia, reactive oxygen species generation, hypothalamic–pituitary–gonadal axis suppression, and aberrant germ cell methylation collectively impair sperm quality and hormonal balance. Short-chain fatty acids, secondary bile acids, and indole derivatives emerge as pivotal messengers within this crosstalk. Therapeutic approaches targeting the androbactome, namely dietary optimization, probiotic or prebiotic supplementation, and fecal microbiota transplantation, have demonstrated encouraging improvements in sperm parameters and testosterone levels, yet the causal inference is constrained by predominantly cross-sectional designs and limited long-term safety data. Recognizing the androbactome as a modifiable determinant of male fertility may open new avenues for personalized diagnosis, risk stratification, and adjunctive therapy in regard to idiopathic infertility. The integration of multi-omics platforms to characterize microbial and metabolomic signatures promises to enrich diagnostic algorithms and guide precision interventions, but rigorously controlled longitudinal and interventional studies are required to secure a translational impact. Full article

Introduction: Fertility is fundamental to human well-being, significantly impacting both individual lives and societal development. In particular, sperm morphology—referring to the shape, size, and structural integrity of sperm cells—is a key indicator in diagnosing male infertility and selecting viable sperm in assisted reproductive technologies such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI). However, traditional manual evaluation methods are highly subjective and inconsistent, creating a need for standardized, automated systems. Objectives: This study aims to develop a robust and fully automated sperm morphology classification framework capable of accurately identifying a wide range of morphological abnormalities, thereby minimizing observer variability and improving diagnostic support in reproductive healthcare. Methods: We propose a novel ensemble-based classification approach that combines convolutional neural network (CNN)-derived features using both feature-level and decision-level fusion techniques. Features extracted from multiple EfficientNetV2 variants are fused and classified using Support Vector Machines (SVM), Random Forest (RF), and Multi-Layer Perceptron with Attention (MLP-Attention). Decision-level fusion is achieved via soft voting to enhance robustness and accuracy. Results: The proposed ensemble framework was evaluated using the Hi-LabSpermMorpho dataset, which contains 18 distinct sperm morphology classes. The fusion-based model achieved an accuracy of 67.70%, significantly outperforming individual classifiers. The integration of multiple CNN architectures and ensemble techniques effectively mitigated class imbalance and enhanced the generalizability of the model. Conclusions: The presented methodology demonstrates a substantial improvement over traditional and single-model approaches in automated sperm morphology classification. By leveraging ensemble learning and multi-level fusion, the model provides a reliable and scalable solution for clinical decision-making in male fertility assessment. Full article

Phospholipase C zeta (PLCζ) has emerged as a pivotal sperm-specific factor responsible for triggering oocyte activation, a process essential for successful fertilization and early embryogenesis. A narrative review was conducted to examine the molecular architecture and biochemical features of PLCζ, with particular emphasis on how its distinctive structural domains facilitate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP₂) and the induction of calcium (Ca²⁺) oscillations in the oocyte. Notably, PLCζ exhibits unique sensitivity to basal Ca²⁺ levels and the capacity to sustain repetitive intracellular Ca²⁺ transients that drive meiotic progression and block polyspermy. Clinically, PLCζ deficiency—whether caused by genetic mutations, reduced expression, or improper localization—represents a unifying explanation for certain forms of male infertility, including total fertilization failure (TFF) following intracytoplasmic sperm injection (ICSI). Globozoospermia is a prime example; this condition is characterized by round-headed sperm devoid of acrosomes and exhibiting significantly reduced or absent PLCζ and often results in fertilization failure. Diagnostic methods such as immunofluorescence, Western blotting, and the mouse oocyte-activation test collectively support the identification and characterization of PLCζ-related defects, while genetic testing for mutations in the PLCZ1 gene has proven valuable for identifying hereditary causes of sperm-borne oocyte-activation deficiency (OAD). Therapeutic approaches range from assisted oocyte activation (AOA) with calcium ionophores to emerging interventions that introduce functional PLCζ protein or mRNA directly into the oocyte. These advancements demonstrate the rapid translation of foundational discoveries into clinically actionable interventions. Future investigations are poised to refine diagnostic assays, standardize measurement protocols, and explore the potential of gene therapy or CRISPR/Cas9-mediated correction for heritable PLCζ abnormalities. By addressing both the molecular basis and translational applications of PLCζ, recent findings underscore its indispensable role in fertility care and lay out a path toward further innovation in assisted reproductive technologies. Full article

Background and Purpose: Undescended testes (UDT) is recognized as the most prevalent anomaly of the male genitalia and presents a significant risk factor for long-term complications, including infertility and testicular cancer. Currently, there is no consensus on the necessity of imaging in the management of UDT, nor is there agreement on which imaging modality is preferred or to what extent these tests offer real added value in the clinical setting. This review aims to evaluate the various imaging options available in the management of cryptorchidism, discussing their utility, advantages, and disadvantages compared to exploratory laparoscopy. Methods: We conducted a PubMed search using the following search terms: [“undescended testis”] OR [(“cryptorchidism”) OR (“diagnostic imaging”)] OR [(“Ultrasound”), OR (“CT scan”) OR (“MRI”)] AND [“laparoscopy”]. We analyzed 90 full articles, excluding irrelevant ones, and, in total, 18 publications were included in this review. Results: Ultrasound (US) is the most commonly used technique due to its non-invasive nature and absence of ionizing radiation. It is particularly beneficial in cases of non-palpable UDT. However, its main limitation lies in the difficulty in accurately locating UDT, especially when they are situated outside the inguinal region. Computed tomography (CT) scans serve as a crucial diagnostic tool, particularly for testes located below the internal inguinal ring. While CT exhibits comparable accuracy in detecting UDT, the need for sedation or general anesthesia, along with the costs and potential risks of secondary malignancy due to radiation exposure, does not favor its routine use. Magnetic resonance imaging (MRI) offers higher sensitivity than US and does not utilize ionizing radiation or intravascular contrast agents. It allows for the generation of multiplanar images, thereby providing improved tissue characterization. However, limitations include prolonged scan durations, the potential for motion artifacts during imaging, the need for sedation, and higher costs. Laparoscopy has been shown to provide better accuracy, offering both diagnostic and therapeutic benefits, particularly in cases of non-palpable UDT. It is widely regarded as the gold standard in achieving clear diagnostic and definitive therapeutic procedures and has demonstrated its utility in determining the anatomical position of intra-abdominal testes, owing to its magnification capabilities and minimally invasive approach. Conclusions: Achieving a correct and comprehensive diagnosis of cryptorchidism requires the medical team to decide on the appropriate imaging studies, as these will not significantly influence or alter the therapeutic decision-making process. It is unlikely that medical practice will eliminate imaging studies before a surgical decision is made in the near future. Therefore, a multidisciplinary approach that includes clinical examination, imaging, and diagnostic laparoscopy remains essential for the accurate management of UDT. Full article

Male infertility is often linked to sperm quality issues; however, the mechanisms behind these alterations remain unclear in certain contexts. This study investigates the impact of anomalous Rho GTPase activation—a process triggered by bacterial toxins—on human sperm structure and function. Human spermatozoa were exposed in vitro to a Rho GTPase activator derived from Escherichia coli under both capacitating and non-capacitating conditions. The results showed increased RhoA GTPase activity in non-capacitating conditions, without affecting viability or mitochondrial membrane potential. However, progressive motility decreased across both conditions, while non-progressive motility and acrosome reaction rates increased. Additionally, intracellular calcium levels rose exclusively in non-capacitating conditions. Structural analysis revealed an increase in abnormal sperm morphology, particularly vacuoles in the sperm head. These findings highlight that anomalous Rho GTPase activation disrupts essential processes like motility and capacitation, which are crucial for successful fertilization. This study provides novel insights into how bacterial infections may induce sperm damage, proposing that Rho GTPase activity could serve as a biomarker for evaluating sperm quality in cases of infertility linked to urogenital infections. Understanding these mechanisms may improve diagnostic and therapeutic approaches for male infertility associated with bacterial pathogens. Human spermatozoa were exposed in vitro to a Rho GTPase activator derived from Escherichia coli under both capacitating and non-capacitating conditions. Full article

MicroRNAs (miRNAs), a class of small noncoding RNAs, play a crucial role in spermatogenesis. However, their specific expression patterns in azoospermic patients, particularly in relation to sperm presence and pregnancy outcomes, remain underexplored. We performed small RNA sequencing on forty testicular tissue samples from idiopathic azoospermic and cryptozoospermic patients who underwent testicular sperm extraction (TESE). Differentially expressed (DE) miRNAs were identified across groups with high, rare, or no spermatozoa presence, as well as between individuals with successful and unsuccessful pregnancies following assisted reproduction. Functional enrichment analyses were conducted to assess the biological relevance of miRNA alterations. Our findings revealed distinct miRNA expression patterns linked to sperm presence and pregnancy outcomes. Samples with high sperm presence exhibited reduced miRNA expression, while those with impaired spermatogenesis demonstrated upregulated miRNAs associated with cell survival and differentiation pathways. Several regulatory pathways were also disrupted in samples leading to unsuccessful pregnancies, including the estrogen signaling receptor (ESR) pathway, interleukin-4 and interleukin-13 signaling, and transcription networks. This study highlights miRNA-mediated regulatory differences in azoospermic patients, identifying potential biomarkers for sperm retrieval success and fertility outcomes. Future validation and multi-omics approaches are needed to confirm these findings and enhance male infertility diagnostics. Full article

Retrograde ejaculation (RE) is a condition where the forward expulsion of seminal fluid is impaired, leading to infertility and psychological distress in affected individuals. This narrative review examines the etiology, pathophysiology, diagnosis, and management of RE, emphasizing its impact on male fertility. RE may result in the partial or complete absence of the ejaculate. Causes of RE include anatomical, neurological, pharmacological, and endocrine factors, with common triggers such as diabetes, spinal cord injury, and prostate surgery. Diagnosis primarily involves the patient history, a laboratory analysis of post-ejaculatory urine samples, and advanced imaging techniques. Management strategies for RE include pharmacological interventions, surgical approaches, and assisted reproductive technologies (ARTs). Sympathomimetic and parasympatholytic agents have demonstrated some success but are limited by side effects and variability in outcomes. ARTs, particularly with sperm retrieved from post-ejaculatory urine, offer a viable alternative for conception, with techniques such as urine alkalization and advanced sperm processing showing promising results. Despite these advancements, treatment efficacy remains inconsistent, with many studies relying on small sample sizes and lacking robust clinical trials. Future research should focus on refining diagnostic tools, optimizing ART protocols, and developing minimally invasive treatments. By addressing these gaps, healthcare providers can improve fertility outcomes and the quality of life for patients with RE. Full article

Background/Objectives: Male infertility is a complex, multifactorial condition influenced by infectious, inflammatory, and autoimmune components. Immunological factors, though implicated in reproduction, remain poorly understood. This study aims to deepen the understanding of infections, inflammation, and autoimmune factors in male infertility, with a focus on immune-related disorders affecting the testes and epididymis—immunologically privileged but vulnerable sites. These factors can impair sperm quality through oxidative stress (ROS) and antisperm antibodies (ASA), further compromising fertility. Methods: A narrative review was conducted by analyzing scientific literature from the past 10 years conducted on PubMed using keywords such as “male infertility”, “autoimmunity”, and “inflammatory disease”. Studies focusing on testicular and epididymal disorders, immunological impacts, and therapeutic approaches were included. Results: Our research highlights that conditions like epididymitis, vasectomy, testicular trauma, and previous surgeries can trigger inflammatory responses, leading to ASA formation and oxidative stress. ASA, particularly sperm-immobilizing antibodies, inhibits sperm motility and migration in the female reproductive tract. Infections caused by sexually transmitted bacteria or urinary pathogens frequently induce epididymo-orchitis, a primary contributor to male infertility. While standardized methodologies for ASA testing remain elusive, assisted reproductive treatments such as intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and intrauterine insemination (IUI) show promise in overcoming immune-mediated infertility. Conclusions: This review underscores the critical role of infection, inflammation, and autoimmune responses in male infertility. It highlights the necessity of improving diagnostic methods, understanding immune-pathological mechanisms, and addressing medicolegal issues associated with male infertility. This knowledge could pave the way for innovative therapies, ultimately enhancing fertility outcomes, and mitigating the societal and legal repercussions of infertility. Full article

A eutopic endometrium in endometriosis shows altered immune responses, including abnormalities of NK cells and expression of plasma cells, related to reproductive issues. This study investigated the counts of CD56-positive NK cells and CD138-positive plasma cells in the basal decidua of term placentas in singleton pregnancies after endometriosis-related infertility conceived by assisted reproductive technology (ART). This single-center, case-control study involved immunohistochemical analysis of CD56-positive NK cells and CD138-positive plasma cells in basal decidua using primary monoclonal mouse antibodies, followed by secondary antibodies using a standardized protocol. CD56 and CD138 immunohistochemically positive cells were reported as the total cell count for each studied antibody expressed per 1 mm² of basal decidua (Olympus BX46 and Olympus Image Analyzer). Placental samples containing basal decidua from 36 participants with endometriosis-related infertility who conceived by ART, 31 participants with male factor infertility who conceived by ART and 40 healthy controls were included. Endometriosis decidua showed the lowest median count of CD56-positive NK cells (11.5 / mm², p = 0.039) in BD compared to male factor group (25 / mm²) and healthy controls (24.5 / mm²). No differences were found for CD138-positive plasma cells counts between study groups. Basal decidua in pregnancies after endometriosis-related infertility showed reduced total count of CD56-positive NK cells, without differences in the CD138-positive plasma cell counts compared to control groups. Future studies should investigate how changes in NK cells throughout pregnancy affect the development of perinatal complications and placental pathologies in women with endometriosis, which could uncover potential diagnostic and therapeutic targets. Full article

Background and Objective: Unexplained infertility is a major challenge in reproductive medicine and requires advanced diagnostic approaches to identify the underlying factors accurately. This study aims to evaluate the utility of risk factor analysis and a gene panel in diagnosing unexplained infertility using the next-generation sequencing (NGS) technology. Our study aimed to characterize and identify risk and genetic factors associated with unexplained infertility. Materials and methods: A cohort of patients with unexplained infertility was comprehensively screened for risk factors and genetic variations using a targeted gene panel (10 couples with unexplained infertility (UI) and 36 fertile couples). 108 articles were selected (58 on female infertility and 50 on male infertility) presenting genes that may be associated with unexplained infertility. A gene panel for unexplained infertility was compiled based on the literature data. A customized virtual panel was created from the exome sequencing data. Results: In the female group, controls had a higher mean age, while in the male patients, both groups were similar in terms of age. Both gender groups had comparable BMI values. No significant associations (p > 0.05) between risk factors and unexplained infertility were found when evaluating anthropometric parameters and other sociodemographic characteristics. In two male patients (20%), a molecular defect was detected in NGS variants classified aspossible benign and probably benign In particular, missense variants were identified in the UGT2B7 and CATSPER2 genes, A molecular defect classified as probably damaging was found in five female patients (50%). In particular, missense variants were identified in the CAPN10, MLH3, HABP2, IRS1, GDF9, and SLC19A1 genes. Conclusions: The study emphasizes that unexplained infertility is often related to mechanisms beyond causative mutations and highlights the need for integrative genomic research involving broader gene panels and multi-faceted approaches, including transcriptomics and epigenetics, to uncover latent genetic predispositions. Full article