Andrology最新文献

{"title":"A CCNA1 Missense Variant Associated With Chromatid Non-Disjunction in Abnormal-Headed Sperm and Male Infertility.","authors":"Aurore Perrin, Frédéric Morel, Zeina Wehbe, Cynthia Frapsauce, Nadia Gueganic, Corinne Tous, Séverine Commet, Laura Dijols, Audrey Basinko, Nathalie Douet-Guilbert, Célia Tebbakh, Zine-Eddine Kherraf, Pierre F Ray, Charles Coutton, Guillaume Martinez","doi":"10.1111/andr.70387","DOIUrl":"https://doi.org/10.1111/andr.70387","url":null,"abstract":"<p><strong>Background: </strong>Macrozoospermia is a rare form of teratozoospermia characterized by tetraploids, large-headed spermatozoa with multiple flagella, usually caused by bi-allelic AURKC mutations. The etiology of atypical phenotypes with a lower proportion of large headed spermatozoa and single flagella however often remains unresolved.</p><p><strong>Objective: </strong>To investigate the genetic cause of severe sperm-head abnormalities with moderate macrozoospermia without multiflagellated spermatozoa in a patient with repeated ICSI failure. An infertile male with three failed ICSI attempts underwent semen analysis, revealing complete teratozoospermia, including 25% macrocephalic spermatozoa.</p><p><strong>Methods: </strong>Multi-probe FISH targeting chromosomes 13, 18, 21, X, Y assessed chromosomal segregation. Whole-exome sequencing (WES) was performed to identify a candidate variant associated with meiotic abnormalities.</p><p><strong>Results: </strong>FISH analysis revealed a high proportion of spermatozoa with n (23) chromosomes and 2c DNA content, consistent with sister chromatid non-disjunction during meiosis II. WES identified a homozygous missense variation in CCNA1, coding for a protein described to be essential for meiotic progression and chromatin remodeling in male germ cells.</p><p><strong>Discussion: </strong>The variant affects a highly conserved residue within a functional domain and is predicted to be deleterious. This study establishes the first clinical association between CCNA1 mutations and chromatid non-disjunction in human spermatogenesis. It highlights the limitations of current morphology-based diagnostic thresholds and supports cytogenetic and genomic assessment for severe teratozoospermia (especially head abnormalities) and ART failure.</p><p><strong>Conclusion: </strong>Expanding genetic screening panels to include CCNA1 may improve diagnostic precision and clinical management in atypical macrozoospermia cases.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building Families-Implementing Balanced Sexual and Reproductive Health: A Joint IFFS and ISA Scientific Statement.","authors":"Peter Y Liu, Edgar Mocanu, Linda Giudice, Marcos Horton, Meletios P Nigdelis, Antti Perheentupa, Andrea Sansone, Giovanni Corona, Luca Gianaroli, Dimitrios G Goulis","doi":"10.1111/andr.70371","DOIUrl":"https://doi.org/10.1111/andr.70371","url":null,"abstract":"<p><p>One of the main initiatives of the World Health Organization (WHO) is the promotion of Sexual and Reproductive Health (SRH). Sexuality, infertility, and contraception are three interconnected pillars of SRH, each essential for achieving global equity in family planning and family building. This scientific Statement, jointly developed by the International Federation of Fertility Societies (IFFS) and the International Society of Andrology (ISA), advocates for inclusive, evidence-based care for all individuals and couples, regardless of geography or socioeconomic status. The Statement underscores the need to enhance practitioner and policymaker education to support access to infertility evaluations and treatments for both men and women and to promote the availability of comprehensive contraceptive services for all in need. The Statement addresses three core domains: sexuality, infertility, and contraception. It emphasizes a biopsychosocial approach to SRH, highlighting the complex interplay between sexual function and fertility. Infertility is a multifactorial condition requiring early, holistic, and multidisciplinary management, including integrated male and female evaluations, medically assisted reproduction, and fertility preservation strategies. Contraception is explored through the lens of global unmet needs, expanding options for male contraceptives, and the importance of socio-culturally sensitive education and counseling. The joint efforts of the IFFS and ISA call for couple-centered SRH, acknowledging the sociocultural and policy challenges that affect access to care in a region-specific manner. This Statement aims to serve as a clinical and advocacy guide for practitioners and stakeholders, reinforcing that reproductive autonomy and access to care are vital components and duties for policymakers when developing public health strategies.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Testicular Tissue Cryopreservation in Prepubertal Boys: Current Advances, Clinical Feasibility, and Future Directions-A Comprehensive Literature Review.","authors":"Wasim Iyad Ibrahim Alghoul, Omer Raheem, Malak Moones Abedi, Ibrahim Khalil Alabid, Maitha Ibrahim Alhammadi, Tabarak Mustafa Al-Karam, Raghad Jafar Naim Abdelhamid, Abdulrahman Sheiko, Sufyan Siddiqui Mohammed","doi":"10.1111/andr.70390","DOIUrl":"https://doi.org/10.1111/andr.70390","url":null,"abstract":"<p><strong>Background: </strong>Prepubertal boys cannot use semen cryopreservation because mature spermatozoa are not yet produced. Testicular tissue cryopreservation (TTC) is therefore offered to selected high-risk patients as an experimental fertility-preservation procedure that stores spermatogonia and their supporting niche for potential future use.</p><p><strong>Objective: </strong>To integrate the TTC pathway from patient selection and tissue banking through follow-up, fertility restoration, and oncologic safety, while reassessing translational readiness in light of recent first-in-human evidence.</p><p><strong>Methods: </strong>A structured narrative review of 49 publications was conducted using literature updated through August 15, 2026. PubMed was supplemented by targeted journal, publisher, preprint, and reference-list searches. Original human evidence was prioritized, with first-in-human reports classified according to the highest endpoint demonstrated.</p><p><strong>Results: </strong>More than 3000 patients younger than 18 years have undergone TTC internationally, with contemporary cohorts reporting low short-term morbidity and no clinically meaningful treatment delay in appropriately selected patients. Tissue quality may be affected by disease and prior gonadotoxic exposure. First-in-human autologous transplantation of cryopreserved immature testicular tissue demonstrated graft survival, revascularization, complete intragraft spermatogenesis, and rare sperm recovery. Autologous transplantation of cryopreserved testicular cells demonstrated feasible rete-testis delivery without restoration of spermatogenesis at 1 year. Patient-specific germline regeneration has also reached the human primordial germ cell-like cell stage. Malignant contamination remains a major concern, particularly in hematologic malignancies.</p><p><strong>Conclusions: </strong>TTC has entered an early human translational phase but remains investigational. The key challenge is now to achieve reproducible, clinically usable sperm production with proven fertilization competence, healthy live birth, and offspring safety.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Common Medications on Male Fertility: An Updated Systematic Review.","authors":"Lina Jebli, Salomé Gallissian, Roxanne Barèges, Félicia Fournier, Catherine Metzler-Guillemain, Ségolène Prades, Fanny Magnan-Sebag, Jeanne Perrin","doi":"10.1111/andr.70381","DOIUrl":"https://doi.org/10.1111/andr.70381","url":null,"abstract":"<p><strong>Background: </strong>Compared with those of cytotoxic treatments, the potential effects of common medications on the fertility of men trying to conceive currently or planning to conceive in the future are less well described. The use of common medications may modify the gonadotropic axis, spermatogenesis, and epididymal maturation or alter male fertility in other ways and are prescribed much more often compare with cytotoxic treatments.</p><p><strong>Objectives: </strong>Based on our review published in 2017, we systematically reviewed the effects of common medications on male fertility to provide evidence-based recommendations for clinical management and possible fertility preservation in men of reproductive age.</p><p><strong>Materials and methods: </strong>A systematic review of the literature using the PRISMA 2020 methodology was performed. We included only original studies published from 2016 to 2025 that involved human males exposed to noncytotoxic pharmacological treatments and reported outcomes related to male fertility, including spermatogenesis, semen parameters, and reproductive hormone concentrations. The data were synthesized descriptively and organized by pharmacological class and individual drug.</p><p><strong>Results: </strong>Among the 16,310 studies retrieved, 184 were included. In addition to the studies describing the deleterious effects of testosterone, sulfasalazine, anabolic steroids, cyproterone acetate, opioids, sertraline, tramadol, GnRH analogues, and sartan that have already been included in the 2017 review, we focused on new studies with good- to high-level evidence for the harmful effects of drugs such as duloxetine, thiopurines, dutasteride, valganciclovir, efavirenz, valproate, or hydroxyurea on male hormones and/or fertility.</p><p><strong>Conclusions: </strong>In this updated review, evidence-based recommendations for clinical management and for possible fertility preservation or contraception in men of reproductive age receiving common acute or chronic medical treatment are provided, with the goal of making these data more readily available to medical staff.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meiotic Origins of Non-Mosaic Klinefelter Syndrome (47, XXY): Mechanisms, Dimorphism, and Emerging Genetic Susceptibility.","authors":"Matteo Lampitto, Marco Barchi","doi":"10.1111/andr.70384","DOIUrl":"https://doi.org/10.1111/andr.70384","url":null,"abstract":"<p><strong>Background: </strong>Non-mosaic Klinefelter syndrome (47,XXY) arises from sex-specific meiotic mechanisms leading to nondisjunction during gametogenesis. In maternal cases, errors occur predominantly during meiosis I, frequently involving X chromosomes that lack crossovers or exhibit crossovers outside optimal chromosomal locations; this nondisjunction is further exacerbated by advancing maternal age and the subsequent deterioration of cohesins. Conversely, paternal 47,XXY stems primarily from the failure of obligate recombination within the pseudoautosomal region, which is critical for accurate XY segregation.</p><p><strong>Objective: </strong>Drawing on the latest literature, this review transitions from a descriptive account of non-mosaic Klinefelter syndrome (nKS) toward a comprehensive analysis of mechanistic and genomic evidence, establishing a unified framework of sex-specific meiotic vulnerability.</p><p><strong>Methods: </strong>We synthesized recent findings from forward genetic approaches in mouse models with data from human observational and reverse-genetic studies, delineating an updated view of the established and putative mechanisms that modulate sex chromosome segregation.</p><p><strong>Results: </strong>We frame XX and XY nondisjunction as a genetically modulated process rather than a purely stochastic event. The integrated evidence supports a unified framework in which maternal and paternal mechanisms converge primarily on meiotic recombination failure but differ in timing, chromosomal context, and genetic modulation.</p><p><strong>Conclusions: </strong>From a clinical standpoint, identifying the molecular drivers of sex chromosome aneuploidy will enhance genetic counseling and risk stratification. Such insights are poised to facilitate informed reproductive decision-making and timely therapeutic support, ultimately reducing the burden of nKS comorbidities and improving patients' quality of life.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marginal Changes in Semen Quality Over Three Decades (1996‒2022) Among 8320 Men in the Danish Young Men Study (DYMS): Cohort Profile and Trends.","authors":"Lærke Priskorn, Cille Baslund-Storch, Laura S Hansen, Astrid L Beck, Ann H Hansen, Stine A Holmboe, Loa Nordkap, Anne Kirstine Bang, Rune Lindahl-Jacobsen, Christine Dalgård, Anna-Maria Andersson, Tina K Jensen, Anders Juul, Niels Jørgensen","doi":"10.1111/andr.70383","DOIUrl":"https://doi.org/10.1111/andr.70383","url":null,"abstract":"<p><strong>Background: </strong>Since the 1990s, declining sperm counts and increasing testicular cancer rates have raised worldwide concern about male reproductive health, including in Denmark. This prompted a prospective population-based study with annual surveillance of semen quality.</p><p><strong>Objective: </strong>This paper presents a detailed profile of the Danish Young Men Study (DYMS) cohort, including semen quality trends from 1996 to 2022 in the general population, interpreted alongside nationwide trends in testicular cancer.</p><p><strong>Materials and methods: </strong>The data include results of annual cross-sectional examinations (1996‒2022) of a total of 8320 men included from the general population (Copenhagen, Denmark) in relation to compulsory assessment for military service. Men provided semen, urine and blood samples, completed a questionnaire and underwent a physical examination. Temporal trends in semen parameters by examination year were assessed using linear regression. For sperm concentration, trends by birth cohort were further compared with nationwide trends in testicular cancer incidence.</p><p><strong>Results: </strong>The median sperm concentration was 45 million/mL, total sperm count was 141 million, 61% progressively motile and 6.5% morphologically normal spermatozoa. Semen parameters remained relatively stable, but a modest improvement was observed in the most recent period (2017‒2022) compared to 1996‒2000; for example, sperm concentration increased from a median of 44 to 49 million/mL. Across the 26 years, 36% of participants had one or more semen parameters below WHO reference levels. A marginal increase in sperm concentration appeared from the earliest (1976‒1980) to latest birth cohorts (2001‒2004), coinciding with a plateau following the previous increase in testicular cancer incidence among Danish men.</p><p><strong>Discussion and conclusion: </strong>Based on unique surveillance data spanning three decades, we showed persistently low semen quality with some temporal fluctuations among men included from the general population. This pattern aligns with the concomitant plateau in testicular cancer incidence. The modest improvement in semen quality observed in recent years may reflect favourable changes in environmental exposures or lifestyle factors, potentially related to the COVID-19 period. However, this finding should be interpreted cautiously, as it may represent random variation.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148954603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ballelic Variants of TTC-Related Genes Cause Asthenoteratozoospermia With Favorable Clinical Outcomes After ICSI.","authors":"Hui Yu, Dongdong Tang, Jiajun Fang, Meng Gu, Kuokuo Li, Zhicong Chen, Baoyan Wu, Xueping Liu, Hao Geng, Lewen Ruan, Chuan Xu, Yang Gao, Qing Tan, Zongliu Duan, Huan Wu, Rong Hua, Rui Guo, Zhaolian Wei, Ping Zhou, Yuping Xu, Xiaojin He, Gaoyuan Wang, Geng An, Mingrong Lv, Yunxia Cao","doi":"10.1111/andr.70361","DOIUrl":"https://doi.org/10.1111/andr.70361","url":null,"abstract":"<p><strong>Background: </strong>Male infertility is a complex, multifactorial disorder that affects ∼7% of men worldwide. Variants in DNAH and CFAP genes are well-established causes of asthenoteratozoospermia, but the contribution of TTC-family genes (TTC12, TTC21A, TTC29) to sperm dysfunction and ICSI outcome remains poorly documented.</p><p><strong>Objectives: </strong>To investigate the genetic and clinical implications of TTC gene variants in men with asthenoteratozoospermia and to evaluate the ICSI outcomes of affected individuals.</p><p><strong>Materials and methods: </strong>We performed whole-exome sequencing and bioinformatic filtering in 843 men with asthenoteratozoospermia. Candidate variants were validated by Sanger sequencing, and the effects on protein expression were assessed using western blotting and immunofluorescence. Sperm morphology and ultrastructure were examined by light and transmission electron microscopy. Clinical outcomes were evaluated following ICSI treatment, including a total of 18 TTC-variant patients and DNAH1-variant men.</p><p><strong>Results: </strong>Thirteen TTC variants in 11 unrelated patients (1.3%) were identified in this cohort, including two homozygous TTC12 variants, six homozygous plus two compound-heterozygous TTC21A variants, and one homozygous TTC29 variants. Variants induced markedly reduced TTC proteins expression and disorganized axonemes and peri-axonemal structures. Clinical data from ICSI cycles demonstrated that fertilization could be achieved, importantly the first reported live birth for TTC21A variants, although blastocyst rates were lower than in DNAH1-mutated controls.</p><p><strong>Conclusion: </strong>This study not only expanded the genotype-phenotype spectrum of variations in the TTC gene family, but also built a bridge between molecular genetics and clinical application, demonstrating the translational path from gene discovery to effective treatment.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148928729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Need for a Global Registry for Charting the Natural History of Klinefelter Syndrome.","authors":"Malika Alimussina, Joseph McElvaney, Corinna Grasemann, Jillian Bryce, Lise Aksglaede, Claudia Boettcher, Lexi Breen, Francesco Carlomagno, Sabine Hannema, Andrea M Isidori, Inas Mazen, Anna Nordenstrom, S Faisal Ahmed, Angela K Lucas-Herald","doi":"10.1111/andr.70392","DOIUrl":"https://doi.org/10.1111/andr.70392","url":null,"abstract":"<p><strong>Background: </strong>Although Klinefelter Syndrome (KS) represents the most common sex chromosome aneuploidy, several gaps in knowledge persist regarding optimal management of individuals with this condition. Individuals with KS can have a diverse phenotype including endocrine, neurodevelopmental, and cardiovascular manifestations.</p><p><strong>Objectives: </strong>To describe the existing KS cohort within SDMregistries and the development and potential role of the dedicated I-KS module.</p><p><strong>Methods: </strong>Retrospective review of current cases of KS on the SDMregistries.</p><p><strong>Results: </strong>In January 2026, the SDMregistries platform that consists of dedicated registries for a wide range of rare conditions affecting sex development and maturation included a total of 10, 658 individuals and of these, 777 (7%) individuals from 17 countries had karyotypes consistent with 47, XXY or mosaic forms containing an XXY cell line. Considering those with a 47, XXY alone, the median year of birth was 1994 (range 1939, 2025) resulting in a median current age of 32 (1, 87) years. This therefore represents the largest contemporary international cohort of individuals with KS of varying ages across the lifespan currently available worldwide.</p><p><strong>Discussion: </strong>The SDMregistries platform offers a unique opportunity to undertake natural history studies as well as evaluations of treatments in KS through the development of a KS specific registry. Such a registry would support evidence-based, personalized care by identifying which interventions work best for specific subgroups and by informing standardized clinical guidelines. This would also assist with care quality improvement, with benchmarking of care and the possibility to accelerate clinical trials by improving patient identification, recruitment, and selection of meaningful outcome measures. Finally, registry data can strengthen advocacy and policy efforts, supporting improved screening, funding, and access to multidisciplinary care.</p><p><strong>Conclusion: </strong>Continued evaluation of existing data and identification of research priorities remain essential to improving long-term outcomes and quality of life for individuals with KS, with the likelihood of increased ease with the launch of the new I-KS module.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epididymal Versus Testicular Sperm for ICSI in Obstructive Azoospermia: Embryological, Clinical, and Neonatal Outcomes in a Retrospective Cohort.","authors":"Li Lei, Ming Li, Na Zhang, Qingqing Tao, Qin Li, Shengli Lin, Xiulian Ren, Xinjie Zhuang, Ping Liu, Rong Li","doi":"10.1111/andr.70388","DOIUrl":"https://doi.org/10.1111/andr.70388","url":null,"abstract":"<p><strong>Background: </strong>Whether sperm source influences intracytoplasmic sperm injection (ICSI) outcomes in men with obstructive azoospermia (OA) remains uncertain.</p><p><strong>Objective: </strong>To compare embryological, clinical, and neonatal outcomes of ICSI using percutaneous epididymal sperm aspiration (PESA)- versus testicular sperm aspiration (TESA)-derived sperm in men with OA.</p><p><strong>Materials and methods: </strong>This single-center retrospective cohort study enrolled a total of 1368 ICSI cycles from couples diagnosed with OA at a tertiary reproductive medical center between January 2015 and August 2022. Embryological outcomes were analyzed in 1368 ICSI cycles (PESA, n = 516; TESA, n = 852). Clinical outcomes were evaluated in 869 fresh day-3 cleavage-stage embryo transfer cycles (PESA, n = 399; TESA, n = 470). Neonatal outcomes were assessed among 262 singleton live births following fresh day-3 embryo transfer (PESA, n = 128; TESA, n = 134). Multivariable regression models were used to adjust for prespecified covariates.</p><p><strong>Results: </strong>In adjusted analyses, TESA (vs. PESA) was associated with a lower 2-pronuclear (2PN) fertilization rate (β = -0.03, p = 0.010) and a lower usable embryo rate (β = -0.12, p < 0.01). In the fresh day-3 transfer cohort, sperm source was not significantly associated with clinical pregnancy, miscarriage, or live birth per transfer (all p > 0.05). Among singleton live births, TESA was associated with lower birth weight (β = -209.01 g, p < 0.01) and lower odds of large for gestational age (OR = 0.45, p = 0.03), whereas gestational age, preterm birth, and small for gestational age were similar between groups.</p><p><strong>Discussion: </strong>PESA was associated with better early embryological outcomes, but these differences did not translate into improved clinical pregnancy or live birth rates. Differences in neonatal growth were also observed, which remain to be further verified in subsequent studies.</p><p><strong>Conclusion: </strong>In men with OA undergoing ICSI and PESA- and TESA-derived sperm showed distinct embryological and neonatal growth characteristics, which merits clinical attention. The choice between PESA and TESA should therefore be individualized according to the clinical context and patient-specific considerations.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactate-Responsive Glycogen Dynamics Are Associated With Bull Sperm Motility and Fertilization Under Glucose-Limited Conditions.","authors":"Md Faizul Hossain Miraz, Takahiro Yamanaka, Takashi Umehara, Shahrina Akter, Wambugu Enoc Njoroge, Masayuki Shimada","doi":"10.1111/andr.70386","DOIUrl":"https://doi.org/10.1111/andr.70386","url":null,"abstract":"<p><strong>Background: </strong>Mammalian sperm need to undergo hyperactivation, capacitation, and acrosome reaction to achieve fertilization competence. However, the female reproductive tract presents contrasting metabolic environments. The uterus is glucose-rich, and the oviduct is lactate-rich and glucose-limited. Furthermore, our previous study reported that lactate plays a regulatory role in glucose metabolism through suppressing glucose uptake and glycolysis. How bull sperm maintain glycolysis-associated functions when exogenous glucose is limited remains unclear.</p><p><strong>Objectives: </strong>To characterize lactate-responsive changes in sperm glycogen content and determine whether CP91149-sensitive processes are associated with glycolysis-related sperm functions and cleavage after in vitro fertilization (IVF) under glucose-limited conditions.</p><p><strong>Materials and methods: </strong>Fresh bull ejaculates were incubated in substrate-free HTF medium to deplete the stored energy. The energy-depleted sperm were treated with lactate, followed by lactate withdrawal and subsequent incubation with glycogen phosphorylase inhibitor (CP91149) in the presence or absence of glucose. Sperm motility, kinematics, acrosome integrity, metabolic flux, glycogen level, and cleavage were evaluated in vitro.</p><p><strong>Results: </strong>Lactate pretreatment prolonged sperm motility under substrate depletion. Lactate withdrawal increased a hyperactivated-like motility subpopulation. Flow cytometry showed that the lactate withdrawal increased membrane permeability of sperm and elevated the percentage of acrosome-reacting sperm. Glycolytic activity of sperm was increased after withdrawal, but the induction was suppressed by the glycogen phosphorylase inhibitor CP91149. Lactate increased sperm glycogen content, which declined after withdrawal. Immunoblotting and immunofluorescence detected proteins associated with gluconeogenesis and glycogen metabolism in bull sperm. CP91149 reduced motility after lactate withdrawal in a dose-dependent manner, and glucose supplementation restored motility. Under glucose-free IVF conditions, CP91149 reduced the post-IVF functional outcome, which was restored by glucose supplementation.</p><p><strong>Discussion and conclusion: </strong>These findings show lactate-responsive changes in sperm glycogen content and a CP91149-sensitive phenotype affecting glycolytic activity, motility, and the post-IVF functional outcome. The data are consistent with a contribution of endogenous glycogen-derived substrates to sperm function under glucose-limited conditions.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}