Search Results (35)

Male infertility affects nearly 15% of couples worldwide, with chromosomal abnormalities representing a major underlying cause. This review explores how numerical and structural chromosomal anomalies, along with environmental exposures, lifestyle factors, and age-related genetic changes, disrupt spermatogenesis and contribute to infertility. It synthesizes findings from cytogenetic, molecular, and clinical studies, with particular focus on mechanisms such as meiotic nondisjunction, spindle assembly checkpoint dysfunction, and alterations in cohesin and synaptonemal complex proteins. Chromosomal abnormalities, both numerical and structural, emerge as key contributors to male infertility by impairing chromosomal segregation and recombination, often leading to azoospermia or oligospermia. Meiotic checkpoint failures and recombination errors further exacerbate the production of aneuploid sperm. Environmental toxins, oxidative stress, and poor nutrition disrupt hormonal balance and chromatin integrity, while advancing paternal age is associated with increased sperm aneuploidy and impaired meiotic control, with implications for assisted reproduction. Specific syndromes, including AZF deletions, Kallmann syndrome, and 46,XX testicular DSD, exemplify the direct genetic impact on male fertility. Overall, chromosomal abnormalities are central to the pathophysiology of male infertility, arising from intrinsic meiotic errors as well as extrinsic environmental and lifestyle factors. Integrating cytogenetic diagnostics, genetic counseling, and lifestyle interventions is essential for comprehensive fertility assessment and management. Further research into molecular biomarkers and targeted therapies could enhance diagnosis, improve treatment strategies, and lead to better reproductive outcomes. Full article

Reproductive strategies represent a fundamental aspect of life-history evolution and are shaped by environmental heterogeneity across geographic gradients. This study investigated geographic variation in reproductive traits of the swelled vent frog (Nanorana quadranus), a stream-breeding species in China’s Qinling–Daba Mountains. Male reproductive traits were assessed across 10 populations, including testicular asymmetry, relative testis size, sperm morphology, and sperm count. Female reproductive traits were examined in 12 populations, focusing on body mass and absolute fecundity. Results indicated no significant difference in bilateral testicular asymmetry (p > 0.05). Both relative testis size and sperm count increased with latitude. Sperm length correlated positively with testis size. Conversely, female body mass and age increased with altitude, while absolute fecundity was positively correlated with body mass. Environmental analysis revealed that sperm length exhibited significant positive correlations with aspect and seasonal evapotranspiration anomaly (SEA). Relative testis size was regulated by mean diurnal temperature range (Bio2) and precipitation of the wettest month (Bio13). Furthermore, female absolute fecundity correlated with the minimum temperature of the coldest month (Bio6). These findings demonstrate that reproductive strategies in N. quadranus adapt to geographic and environmental gradients, reflecting adaptive plasticity to local ecological pressures. This study advances understanding of amphibian reproductive adaptation and highlights the importance of incorporating environmental factors in life-history research. Full article

Background: Artificial intelligence (AI) and machine learning (ML) have been reshaping maternal, fetal, neonatal, and reproductive healthcare by enhancing risk prediction, diagnostic accuracy, and operational efficiency across the perinatal continuum. However, no comprehensive synthesis has yet been published. Objective: To conduct a scoping review of reviews of AI/ML applications spanning reproductive, prenatal, postpartum, neonatal, and early child-development care. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, and Scopus through April 2025. Two reviewers independently screened records, extracted data, and assessed methodological quality using AMSTAR 2 for systematic reviews, ROBIS for bias assessment, SANRA for narrative reviews, and JBI guidance for scoping reviews. Results: Thirty-nine reviews met our inclusion criteria. In preconception and fertility treatment, convolutional neural network-based platforms can identify viable embryos and key sperm parameters with over 90 percent accuracy, and machine-learning models can personalize follicle-stimulating hormone regimens to boost mature oocyte yield while reducing overall medication use. Digital sexual-health chatbots have enhanced patient education, pre-exposure prophylaxis adherence, and safer sexual behaviors, although data-privacy safeguards and bias mitigation remain priorities. During pregnancy, advanced deep-learning models can segment fetal anatomy on ultrasound images with more than 90 percent overlap compared to expert annotations and can detect anomalies with sensitivity exceeding 93 percent. Predictive biometric tools can estimate gestational age within one week with accuracy and fetal weight within approximately 190 g. In the postpartum period, AI-driven decision-support systems and conversational agents can facilitate early screening for depression and can guide follow-up care. Wearable sensors enable remote monitoring of maternal blood pressure and heart rate to support timely clinical intervention. Within neonatal care, the Heart Rate Observation (HeRO) system has reduced mortality among very low-birth-weight infants by roughly 20 percent, and additional AI models can predict neonatal sepsis, retinopathy of prematurity, and necrotizing enterocolitis with area-under-the-curve values above 0.80. From an operational standpoint, automated ultrasound workflows deliver biometric measurements at about 14 milliseconds per frame, and dynamic scheduling in IVF laboratories lowers staff workload and per-cycle costs. Home-monitoring platforms for pregnant women are associated with 7–11 percent reductions in maternal mortality and preeclampsia incidence. Despite these advances, most evidence derives from retrospective, single-center studies with limited external validation. Low-resource settings, especially in Sub-Saharan Africa, remain under-represented, and few AI solutions are fully embedded in electronic health records. Conclusions: AI holds transformative promise for perinatal care but will require prospective multicenter validation, equity-centered design, robust governance, transparent fairness audits, and seamless electronic health record integration to translate these innovations into routine practice and improve maternal and neonatal outcomes. Full article

Background and Objectives: Pregnancies resulting from assisted reproductive technology (ART) have been associated with placenta-related adverse outcomes. Uterine artery Doppler pulsatility index (UtA-PI) reflects placental function. This study aimed to examine whether second-trimester UtA-PI differs according to the conception method after adjusting for potential confounding factors. Materials and Methods: In this retrospective cohort study, we included data from February 2015 to August 2024, at the third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, on singleton pregnancies presenting for their routine antenatal care, including a second-trimester anomaly scan. Pregnancies conceived via ART, including those conceived via ovulation induction/intrauterine insemination (OI/IUI) or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), were compared to those conceived spontaneously. Multiple linear regression was employed to investigate the association between the mode of conception and log₁₀ UtA-PI values, adjusting for various confounders, including gestational age at the time of the scan, maternal weight, height, age, parity, mode of delivery, smoking status, pre-existing diabetes mellitus (type I or II), and pre-existing thyroid disease. Results: The study included 15,552 singleton pregnancies, of which 82 (0.5%) were conceived via OI/IUI and 690 (4.4%) were conceived via IVF/ICSI. The median UtA-PI values were 0.99 (IQR: 0.85–1.17) for spontaneous conception (SC), 1.00 (IQR: 0.86–1.16) for OI/IUI, and 0.90 (IQR: 0.76–1.12) for IVF/ICSI. The Kruskal–Wallis test indicated a statistically significant difference among these groups (p < 0.001). Pairwise comparisons using the Wilcoxon rank-sum test with Bonferroni correction revealed that UtA-PI values in IVF/ICSI pregnancies were significantly lower compared to both SC and OI/IUI pregnancies (p < 0.001 for both). No significant difference was observed between the SC and OI/IUI groups. In the multivariable linear regression model, IVF/ICSI conception was independently associated with lower log₁₀ UtA-PI values (estimate = −0.076, 95% CI: −0.096, −0.056) while no association was found for OI/IUI conception. Conclusions: Although ART has been associated with placental-related complications, mid-trimester UtA flow was found to be lower in IVF/ICSI pregnancies, suggesting better utero-placental flow in ART pregnancies and other possible mechanisms in the maternal–placental interplay for the development of pregnancy complications. Full article

Male reproductive aging proceeds gradually and involves complex alterations across germ cells, somatic cells, and the testicular niche. Multi-omics analyses highlight shifts in spermatogonial stem cell dynamics, diminished sperm quantity and quality, and reconfigured support from Sertoli and Leydig cells. These somatic cells show numerical declines and exhibit senescence-associated changes that amplify inflammatory signals and compromise blood–testis barrier integrity. Concurrently, fibrosis and heightened immune cell infiltration disrupt intercellular communication, contributing to further deterioration of spermatogenesis. Epigenetic remodeling—including DNA methylation drift, histone modification imbalances, and altered small non-coding RNA profiles—adds another dimension, reducing sperm integrity and potentially exerting transgenerational effects on offspring health. Observed hormonal changes, such as reduced testosterone and INSL3 production by aging Leydig cells, reflect the additional weakening of testicular function. These multifactorial processes collectively underlie the drop in male fertility and the increased incidence of adverse outcomes, such as miscarriages and developmental anomalies in the offspring of older fathers. Research into mitigation strategies, including interventions targeting senescent cells, oxidative stress, and inflammatory pathways, may slow or reverse key mechanisms of testicular aging. These findings underscore the importance of understanding the molecular hallmarks of male reproductive aging for preserving fertility and safeguarding offspring well-being. 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

Barth syndrome (BTHS) is a rare, infantile-onset, X-linked mitochondriopathy exhibiting a variable presentation of failure to thrive, growth insufficiency, skeletal myopathy, neutropenia, and heart anomalies due to mitochondrial dysfunction secondary to inherited TAFAZZIN transacetylase mutations. Although not reported in BTHS patients, male infertility is observed in several Tafazzin (Taz) mouse alleles and in a Drosophila mutant. Herein, we examined the male infertility phenotype in a BTHS-patient-derived D75H point-mutant knockin mouse (Taz^PM) allele that expresses a mutant protein lacking transacetylase activity. Neonatal and adult Taz^PM testes were hypoplastic, and their epididymis lacked sperm. Histology and biomarker analysis revealed Taz^PM spermatogenesis is arrested prior to sexual maturation due to an inability to undergo meiosis and the generation of haploid spermatids. Moreover, Taz^PM testicular mitochondria were found to be structurally abnormal, and there was an elevation of p53-dependent apoptosis within Taz^PM seminiferous tubules. Immunoblot analysis revealed that Taz^PM gamete genome integrity was compromised, and both histone γ-H2Ax and Nucleoside diphosphate kinase-5 protein expression were absent in juvenile Taz^PM testes when compared to controls. We demonstrate that Taz-mediated transacetylase activity is required within mitochondria for normal spermatogenesis, and its absence results in meiotic arrest. We hypothesize that elevated Taz^PM spermatogonial apoptosis causes azoospermia and complete infertility. Full article

Background and Objectives: Recurrent pregnancy loss (RPL) is a multifactorial condition, encompassing genetic, anatomical, immunological, endocrine, as well as infectious and environmental factors; however, the etiology remains elusive in a substantial number of cases. Genetic factors linked to RPL include parental karyotype abnormalities (e.g., translocations, inversions, copy number variants), an increase in sperm aneuploidy, fetal microchimerism, severe skewing of X chromosome inactivation, and various gene polymorphisms. Our study aims to explore the value of routine conventional parental karyotyping in couples with RPL. Materials and Methods: A total of 213 couples (426 individuals) with a history of RPL were enrolled in this retrospective study. The peripheral blood samples included in this study were referred to the Human Genomics Laboratory of the University of Medicine and Pharmacy in Craiova, Romania, for conventional cytogenetic analysis between January 2013 and December 2023, by the Outpatient Medical Genetics Clinic of the Emergency Clinical County Hospital of Craiova. Chromosome analysis was performed using standard protocols and karyotypes were reported according to ISCN. Results: Out of 426 patients provided with conventional G-banded chromosome analysis, 410 had a normal karyotype (96.2%) and 16 had chromosome abnormalities (3.8%). The most common chromosomal abnormalities were reciprocal and Robertsonian translocations, with chromosomes 8, 11, 14, and 21 being most frequently involved. A single numerical anomaly was detected (47,XYY). One or multiple chromosomal polymorphisms were identified in 104 subjects (24.4%). In addition, we conducted a stratified analysis of the unselected group and detected chromosome abnormalities in only four cases (0.94%). Conclusions: Our results are consistent with recommendations for paternal karyotyping after an individual risk assessment in instances such as a previous live birth with congenital anomalies and/or the detection of unbalanced chromosomes or a translocation in product of conception or chorionic villi/amniotic fluid samples. In the absence of a positive history, blindly karyotyping couples may prove too expensive and labor intensive, while providing no information on fertility status or live birth rates. Full article

Pre-implantation genetic testing (PGT) is a crucial process for selecting embryos created through assisted reproductive technology (ART). Couples with chromosomal rearrangements, infertility, recurrent miscarriages, advanced maternal age, known single-gene disorders, a family history of genetic conditions, previously affected pregnancies, poor embryo quality, or congenital anomalies may be candidates for PGT. Preimplantation genetic testing for aneuploidies (PGT-A) enables the selection and transfer of euploid embryos, significantly enhancing implantation rates in assisted reproduction. Fluorescence in situ hybridization (FISH) is the preferred method for analyzing biopsied cells to identify these abnormalities. While FISH is a well-established method for identifying sperm aneuploidy, NGS offers a more comprehensive assessment of genetic material, potentially enhancing our understanding of male infertility. Chromosomal abnormalities, arising during meiosis, can lead to aneuploid sperm, which may hinder embryo implantation and increase miscarriage rates. This review provides a comparative analysis of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) in sperm evaluations, focusing on their implications for preimplantation genetic testing. This analysis explores the strengths and limitations of FISH and NGS, aiming to elucidate their roles in improving ART outcomes and reducing the risk of genetic disorders in offspring. Ultimately, the findings will inform best practices in sperm evaluations and preimplantation genetic testing strategies. Full article

(1) Background: Nonobstructive azoospermia (NOA) etiologies affect the sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) and the clinical outcomes following intracytoplasmic sperm injection (ICSI); (2) Methods: We investigated seven NOA etiologies. The SRR and clinical outcomes of 627 patients were analyzed between November 2017 and July 2022 in the Reproductive and Genetic Hospital of China International Trust and Investment Corporation-Xiangya (CITIC-Xiangya); (3) Results: The overall SRR was 39.4% (247/627). The SRR according to NOA etiologies were: Y chromosome azoospermia factor c microdeletions (26/46, 56.5%), Klinefelter syndrome (KS), 36/85, 42.4%), idiopathic (110/398, 27.6%), cryptorchidism (20/29, 69.0%), chromosome anomalies (7/13, 53.9%), orchitis (45/50, 90.0%), and cancer (3/6, 50.0%). The SRR were different for spermatogonia arrest (26/96, 27.1%), maturation arrest (76/177, 42.9%), and SCOS (30/80, 37.5%) according to histological examinations. The clinical pregnancy rate was similar among the NOA etiologies. The high-quality embryo rate differed between successful (54.7%) and unsuccessful (40.9%) pregnancies. Moreover, the successfully pregnant women (28.99 years) were younger than the unsuccessfully pregnant ones (30.92 years); (4) Conclusions: The SRR from patients with NOA was associated with the etiology and histological categories, while the clinical outcome was associated with the high-quality embryo rate and the female partner’s age. Full article

Objectives: Evaluate the prevalence of genetic factors in a large population of infertile subjects and define the seminological, hormonal, and ultrasonographic features for each alteration. Methods: This single-center retrospective study included male partners of infertile couples undergoing genetic investigations due to oligozoospermia or azoospermia evaluated from January 2012 to January 2022. The genetic investigations consist of karyotype, CFTR gene mutations plus variant of the IVS8-5T polymorphic trait, Y chromosome microdeletion, and Next Generation Sequencing panel to analyze genes implicated in congenital hypogonadotropic hypogonadism (CHH). Results: Overall, 15.4% (72/466) of patients received a diagnosis of genetic cause of infertility. Specifically, 23 patients (31.9%) harbor mutations in the CFTR gene, 22 (30.6%) have a 47, XXY karyotype, 14 (19.4%) patients show a Y chromosome microdeletion, 7 (9.7%) have structural chromosomal anomalies, and 6 (8.3%) have CHH. Overall, 80.6% of patients were azoospermic and 19.4% oligozoospermic (sperm concentration 3.5 ± 3.8 million/mL). Almost all patients presented hormonal alterations related to the specific genotype, while the main ultrasound alterations were testicular hypoplasia, calcifications/microcalcifications, and enlarged/hyperechoic epididymis. Conclusions: The prevalence of genetic abnormalities in males of infertile couples was 15.4% in our Center. CFTR gene disease-causing variants resulted in more frequent, with various clinical features, highlighting the complexity and heterogeneity of the presentation. Other investigations are needed to understand if conditions like ring chromosomes and other translocations are related to infertility or are incidental factors. Full article

The volatilome profile of some biofluids (blood, urine, and human semen) identified by Solid-Phase Microextraction–Gas Chromatography/Mass Spectrometry (SPME-GC/MS) and collected from young men living in two high-pollution areas in Italy, i.e., Land of Fires and Valley of Sacco River, have been coupled to sperm parameters obtained by spermiogram analysis to build general multiple regression models. Panels of volatile organic compounds (VOCs) have been selected to optimize the models and used as predictive variables to estimate the different sperm quality parameters (sperm cell concentration, total and progressive motility/immotile cells, total/head/neck/tail morphology anomalies, semen round cell concentration). The results of the multiple linear regression models based on the different subgroups of data joining VOCs from one/two or three biofluids have been compared. Surprisingly, the models based on blood and urine VOCs have allowed an excellent estimate of spermiogram values, paving the way towards a new method of indirect evaluation of semen quality and preventive screening. The significance of VOCs in terms of toxicity and dangerousness was discussed with the support of chemical databases available online. Full article

In recent decades, we have witnessed a progressive decline in male fertility. This is partly related to the increased prevalence of chronic diseases (e.g., obesity and diabetes mellitus) and risky lifestyle behaviors. These conditions alter male fertility through various non-genetic mechanisms. However, there is increasing evidence that they are also capable of causing sperm epigenetic alterations, which, in turn, can cause infertility. Furthermore, these modifications could be transmitted to offspring, altering their general and reproductive health. Therefore, these epigenetic modifications could represent one of the causes of the progressive decline in sperm count recorded in recent decades. This review focuses on highlighting epigenetic modifications at the sperm level induced by non-genetic causes of infertility. In detail, the effects on DNA methylation, histone modifications, and the expression profiles of non-coding RNAs are evaluated. Finally, a focus on the risk of transgenerational inheritance is presented. Our narrative review aims to demonstrate how certain conditions can alter gene expression, potentially leading to the transmission of anomalies to future generations. It emphasizes the importance of the early detection and treatment of reversible conditions (such as obesity and varicocele) and the modification of risky lifestyle behaviors. Addressing these issues is crucial for individual health, in preserving fertility, and in ensuring the well-being of future generations. Full article

Psychotropic drugs and benzodiazepines are nowadays among the primary substances of abuse. This results in a large and constant release into aquatic environments where they have potentially harmful effects on non-target organisms and, eventually, human health. In the last decades, evidence has been collected on the possible interference of benzodiazepines with reproductive processes, but data are few and incomplete. In this study, the possible negative influence of delorazepam on fertilization and embryo development has been tested in Paracentrotus lividus, a key model organism in studies of reproduction and embryonic development. Sperm, eggs, or fertilized eggs have been exposed to delorazepam at three concentrations: 1 μg/L (environmentally realistic), 5 μg/L, and 10 μg/L. Results indicate that delorazepam reduces the fertilizing capacity of male and female gametes and interferes with fertilization and embryo development. Exposure causes anatomical anomalies in plutei, accelerates/delays development, and alters the presence and distribution of glycoconjugates such as N-Acetyl-glucosamine, α-linked fucose, and α-linked mannose in both morulae and plutei. These results should attract attention to the reproductive fitness of aquatic species exposed to benzodiazepines and pave the way for further investigation of the effects they may exert on human fertility. The presence of benzodiazepines in the aquatic environment raises concerns about the reproductive well-being of aquatic species. Additionally, it prompts worries regarding potential impacts on human fertility due to the excessive use of anxiolytics. Full article

Diabetes mellitus is a metabolic disease that can cause systemic problems, including testicular dysfunction. Several diabetes medications have demonstrated potential adverse effects on the male reproductive system; however, the effects of saxagliptin and dapagliflozin have not been sufficiently examined. This investigation studied the impacts of saxagliptin and dapagliflozin treatments on the gonads in a male mouse model of diabetes. Testicular disturbances were assessed by sperm DNA damage, diakinesis-metaphase I chromosome examination, and spermiogram analysis. Our results showed more sperm DNA damage, more spermatocyte chromosome aberrations, lower sperm motility/count, and more sperm morphological anomalies in diabetic mice than in the control mice. Dapagliflozin significantly restored all examined measures to the control values in diabetic mice, unlike saxagliptin, which exacerbated the reduction in sperm count and motility. Both drugs significantly restored the gonadal redox imbalances in diabetic mice by decreasing reactive oxygen species accumulation and increasing glutathione levels. In conclusion, our study presents preliminary evidence for the safety and efficacy of dapagliflozin in alleviating testicular abnormalities induced by diabetes, making it a promising candidate drug for patients with diabetes in their reproductive age. As saxagliptin may have negative effects on fertility, its prescription should be avoided in young male diabetic patients. Full article