Human reproduction最新文献

{"title":"Metabolic imaging for gamete and embryo assessment through advanced microscopy technologies: a novel avenue for artificial intelligence?","authors":"Fabrizzio Horta, Denny Sakkas, Shannon Handley, Yaoxi Xiong, Bettina Mihalas, Rebecca Deans, Roger J Hart, Robert B Gilchrist, Ewa M Goldys","doi":"10.1093/humrep/deag114","DOIUrl":"https://doi.org/10.1093/humrep/deag114","url":null,"abstract":"Infertility affects approximately one in six people globally and demand for ARTs, is expected to rise as parenthood is increasingly delayed. However, ART success remains constrained by gamete and embryo quality, female age, and biological factors beyond chromosomal status alone, highlighting the need for non-invasive methods that can complement current morphology-based and genetic approaches. Because gamete and embryo developmental competence is tightly coupled to cellular metabolism, label-free metabolic imaging has emerged as a promising strategy to assess developmental potential through endogenous autofluorescence of reduced nicotinamide adenine dinucleotide/phosphate [NAD(P)H] and oxidized flavins (FAD), which provide optical proxies of redox balance, mitochondrial activity, and oxidative metabolism. This invited mini-review synthesizes the biochemical basis of NAD(P)H/FAD autofluorescence signals, relates these readouts to the unique metabolic programs of oocytes, embryos across preimplantation development, and sperm, and reviews reproductive studies using fluorescence lifetime imaging microscopy, hyperspectral microscopy, and emerging light-sheet fluorescence microscopy. We discuss practical and interpretive challenges, including modality-dependent signal biases and recent consensus efforts towards standardization. Evidence linking metabolic signatures to reproductive ageing, developmental potential, and embryo ploidy status suggests that metabolic imaging, particularly when paired with artificial intelligence (AI), could enable automated, objective decision support for gamete and embryo selection. Finally, we briefly outline how AI could convert complex metabolic imaging data into clinically interpretable decision-support outputs for embryo ranking and risk stratification. Advances in rapid volumetric imaging, microsystems, and AI may support future ART workflows aimed at improving efficiency, accessibility, and cost-effectiveness.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"67 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem cell-based embryo models: scientific promise clashes with ethical reality.","authors":"Michele Boiani,Hans-Werner Denker","doi":"10.1093/humrep/deag112","DOIUrl":"https://doi.org/10.1093/humrep/deag112","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"443 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148441046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progesterone-based ovulation timing versus LH surge monitoring in true natural cycle frozen embryo transfer: impact on live birth rates in a prospective cohort study","authors":"Turgut Aydin, Nadiye Koroglu, Edis Kahraman, Nazli Albayrak, Elif Kose","doi":"10.1093/humrep/deag109","DOIUrl":"https://doi.org/10.1093/humrep/deag109","url":null,"abstract":"STUDY QUESTION Does progesterone-based embryo transfer timing achieve live birth rates comparable to LH-surge-based timing in true natural cycle frozen embryo transfer (NC-FET)? SUMMARY ANSWER Progesterone-based embryo transfer timing was associated with live birth rates comparable to those achieved with LH surge-based timing in true NC-FET, with no evidence of an independent association between ovulation timing strategy and live birth after adjustment for potential confounders. WHAT IS KNOWN ALREADY In true NC-FET, embryo transfer timing is commonly scheduled according to the LH surge. However, identification of the LH surge may be challenging. Serum progesterone rise may reflect ovulation timing, yet its use as an alternative approach for scheduling embryo transfer in NC-FET cycles remains insufficiently investigated. STUDY DESIGN, SIZE, DURATION This prospective cohort study included 490 true NC-FET cycles performed at a single tertiary IVF center between 2022 and 2025. Cycles were analyzed according to the ovulation timing strategy used for embryo transfer scheduling: progesterone-based timing (n = 286) or LH surge-based timing (n = 204). PARTICIPANTS/MATERIALS, SETTING, METHODS Ovulation was monitored using serial ultrasound and serum hormone measurements. Embryo transfer timing was scheduled according to either detection of the LH surge or the rise in serum progesterone concentrations. The primary outcome was live birth. Adjusted relative risks were estimated using modified Poisson regression with robust standard errors, adjusting for infertility duration and etiology, endometrial thickness at transfer, embryo quality, and number of embryos transferred. Adjusted absolute risk differences were calculated using marginal standardization. An exploratory threshold-based assessment was performed on the risk-difference scale. MAIN RESULTS AND THE ROLE OF CHANCE Live birth occurred in 162 of 286 progesterone-timed cycles (56.6%) and 106 of 204 LH-timed cycles (52.0%) (unadjusted RR 1.09, 95% CI 0.93–1.28). After adjustment, ovulation timing strategy showed no evidence of an independent association with live birth (adjusted RR 1.09, 95% CI 0.93–1.30; P = 0.264). The adjusted absolute risk difference was +4.9% (95% CI −3.8% to +13.6%). Clinical pregnancy, hCG positivity, and miscarriage rates were also comparable between groups. In exploratory analyses, follicle size measured 1 day before ovulation was positively correlated with progesterone levels on the embryo transfer day (Spearman r = 0.36, P < 0.001), and embryo-transfer-day progesterone levels were positively correlated with estradiol levels measured 1 day before ovulation (Spearman r = 0.29, P < 0.001). LIMITATIONS, REASONS FOR CAUTION The observational design may introduce residual confounding despite statistical adjustment. The timing strategy was not randomized and reflected an evolving institutional protocol. In addition, the progesterone thresholds were derived and applied w","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"41 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply: Stem cell-based embryo models: scientific promise clashes with ethical reality.","authors":"Alfonso Martinez Arias,Nicolas Rivron,Shahragim Tajbakhsh,Josephine Johnston,Cantas Alev,Laure Bally-Cuif,Elvan Böke,Tommaso Cavazza,Emma Cave,David Cyranoski,Laurent David,Miguel A Esteban,Jianping Fu,Niels Geijsen,Nienke De Graeff,Jacob H Hanna,Nick Hopwood,Maneesha S Inamdar,Fredrik Lanner,Brigitte Leeners,Zhen Liu,Jean Leon Maitre,Gabriella Minchiotti,Naomi Moris,Megan Munsie,Kathy K Niakan,Olivier Pourquie,Vincent Pasque,Martin Pera,Yaojin Peng,Sophie Petropoulos,Sharad Ramanathan,Janet Rossant,Peter Rugg-Gunn,Mitinori Saitou,Karen Sermon,Jose Silva,Thorold Theunissen,Margherita Turco,John Wallingford,Hongmei Wang,Aryeh Warmflash,Jun Wu,Leqian Yu","doi":"10.1093/humrep/deag113","DOIUrl":"https://doi.org/10.1093/humrep/deag113","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"37 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148441198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germinal vesicle oocytes’ rescue: a worthless treatment or a patient-centred approach? Eight years of clinical experience in poor prognosis patients","authors":"Danilo Cimadomo, Laura Escrich, Lucía Alegre, Noelia Grau, Arancha Galán, Cristina Rodríguez Varela, Marilena Taggi, Sara Pasku, Laura Rienzi, Ernesto Bosch, María-José Escribà","doi":"10.1093/humrep/deag115","DOIUrl":"https://doi.org/10.1093/humrep/deag115","url":null,"abstract":"STUDY QUESTION Does germinal vesicle (GV) rescue by IVM provide a meaningful clinical benefit in patients with unexpectedly low mature oocyte yield, and which patient profiles are most likely to benefit? SUMMARY ANSWER Especially in patients with more GV oocytes obtained, GV rescue increased the number of mature oocytes, zygotes, blastocysts, and euploid embryos per cycle, reduced transfer cancellation, and contributed to a 20% relative increase in cumulative live birth rate. WHAT IS KNOWN ALREADY Immature oocytes retrieved during controlled ovarian stimulation are traditionally discarded due to their reduced developmental competence. Previous studies suggest that GV rescue may increase usable oocytes, but its clinical value, especially within a Pre-implantation Genetic Testing for Aneuploidies (PGT-A) framework, remains unclear. STUDY DESIGN, SIZE, DURATION This retrospective clinical study analysed 8 years of GV rescue experience in a single centre (January 2017–December 2024), including 47 women (<39 years) undergoing ICSI with PGT-A who displayed suboptimal mature oocyte recovery (Metaphase II oocytes (MII) ≤6, maturity rate <80% relative to ≥14 mm follicles at ovulation trigger, and ≥4 GV oocytes). A sub-analysis of available time-lapse videos of rescued GV oocytes and sibling control MII oocytes was conducted to outline morphometric and morphodynamic determinants of rescue and blastulation. PARTICIPANTS/MATERIALS, SETTING, METHODS All retrieved MII oocytes underwent ICSI, whereas GV oocytes were cultured in time-lapse systems for additional 24 h; those rescued (rMII) were inseminated. Outcomes included fertilization, blastulation, morphological quality, euploidy rates, and clinical outcomes after vitrified-warmed euploid blastocyst transfer. Patients’ benefit was defined as obtaining ≥1 euploid blastocyst from rMII. Morphometric features (relevant areas, diameters, perimeters) and morphodynamic parameters (timing of GV breakdown [GVBD], metaphase-I duration and first polar body (PB1) extrusion, second polar body (PB2) extrusion, pronuclei appearance, juxtaposition and fading, and cleavage) were annotated. MAIN RESULTS AND THE ROLE OF CHANCE Among 266 GV oocytes, 53.7% matured to MII, increasing the available MII yield per patient by 75%. Fertilization rates were comparable between MII and rMII, while blastulation was significantly lower for rMII. Nevertheless, rMII-derived blastocysts showed similar morphology and euploidy to controls and contributed ≥1 additional euploid embryo in 11 patients. These patients exhibited higher total cumulus–oocyte complexes, GV count, and superior rMII fertilization and blastulation, although the demographics and basal parameters as well as the sibling control MII competence were comparable. GV rescue contributed to an 8% relative increase in the number of patients with euploid blastocysts and to a 20% relative increase in the number of patients with a live birth. Successfully rescued GV oocyte","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"42 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAPSS2-mediated BMPR1A sulfation in stromal cells regulating endometrial decidualization via autophagy.","authors":"Duo Zi,Wanying Deng,Xiaoli Zhang,Yunfei Li,Junzhi Liang,Jia Hu,Ruizhe Cao,Wenhui Gao,Na Zuo,Hao Chen,Da Li","doi":"10.1093/humrep/deag103","DOIUrl":"https://doi.org/10.1093/humrep/deag103","url":null,"abstract":"STUDY QUESTIONDoes 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2)-mediated sulfation contribute to defective decidualization in patients with recurrent implantation failure (RIF), and what are the underlying mechanisms?SUMMARY ANSWERDownregulation of PAPSS2 enhances the interaction between bone morphogenetic protein receptor type 1A (BMPR1A) and bone morphogenetic protein 2 (BMP2), as well as SMAD family member 1/5/9 (SMAD1/5/9)-dependent autophagic flux, thereby promoting decidualization and increasing the receptivity of endometrial stromal cells to trophoblast invasion.WHAT IS KNOWN ALREADYDecidualization is essential for embryo implantation and pregnancy maintenance, and impaired decidualization is considered a key pathological mechanism underlying RIF. Although protein tyrosine sulfation is a critical post-translational modification, its role in endometrial decidualization remains unclear.STUDY DESIGN, SIZE, DURATIONWe integrated transcriptomic datasets, performed in vitro decidualization assays in immortalized human endometrial stromal cells (T-HESCs) and primary human endometrial stromal cells (hEnSCs), and established an artificial decidualization mouse model. Functional assays and molecular analyses were conducted between 2023 and 2026.PARTICIPANTS/MATERIALS, SETTING, METHODSMid-secretory endometrial tissues were collected from patients with RIF and fertile controls. Decidualization was induced in T-HESCs and primary hEnSCs using dibutyryl-cAMP and progesterone. The effects of PAPSS2 knockdown or overexpression were assessed by RT-qPCR, Western blotting, immunoprecipitation, immunofluorescence, and in vitro implantation assays with BeWo spheroids. In vivo, an ovariectomized mouse model was used to evaluate decidualization under pharmacological modulation of BMP-SMAD signaling and autophagy.MAIN RESULTS AND THE ROLE OF CHANCEWe found that sulfation levels were elevated in endometrial stromal cells from RIF patients. Transcriptomic analysis revealed that PAPSS2, a known sulfation-related gene, was consistently downregulated during decidualization. Mechanistically, PAPSS2 knockdown in endometrial stromal cells decreased BMPR1A sulfation, enhanced its binding affinity for BMP2, and activated the downstream SMAD1/5/9 signaling pathway. Functionally, the activation of this pathway promoted autophagy, thereby enhancing decidualization and increasing stromal cell receptivity to trophoblast invasion.LARGE SCALE DATAPublicly available bulk transcriptomic datasets GSE75425 and GSE17504, together with the single-cell RNA-seq dataset GSE183837, were obtained from the Gene Expression Omnibus (GEO) database.LIMITATIONS, REASONS FOR CAUTIONAlthough our data support dysregulated sulfotyrosine levels and implicate the PAPSS2-BMPR1A sulfation axis in stromal decidualization in RIF, further studies with larger sample sizes are required to confirm their in vivo relevance.WIDER IMPLICATIONS OF THE FINDINGSOur findings reveal a previously unrecognize","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"38 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148408373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L26/P-693 Laboratory–Clinical KPI alignment in POSEIDON 3 and 4 patients: Implications for counselling, predictability, and time to pregnancy","authors":"K.C. Mantravadi, D. Rao, V. Syakasiri","doi":"10.1093/humrep/deag083.1023","DOIUrl":"https://doi.org/10.1093/humrep/deag083.1023","url":null,"abstract":"Study question Do laboratory performance indicators align with pregnancy outcomes in POSEIDON 3 and 4 patients, and can they reliably guide counselling? Summary answer Laboratory indicators demonstrate clear differences between POSEIDON 3 and 4 patients, but do not consistently predict pregnancy and live birth outcomes. What is known already POSEIDON Groups 3 and 4 represent poor-prognosis IVF patients primarily limited by low oocyte numbers. Laboratory key performance indicators (KPIs) such as cycle cancellation, blastocyst formation, and embryo utilisation are commonly used to assess prognosis and guide counselling regarding expected success, number of cycles, and embryo pooling strategies. However, whether favourable laboratory performance translates predictably into pregnancy, miscarriage, and live birth outcomes remains unclear. The relationship between laboratory KPIs and reproductive outcomes in poor-prognosis patients has not been well characterised. Study design, size, duration This retrospective cohort study analysed IVF cycles performed between 2014–2024 at a tertiary fertility centre. A total of 1,250 women classified as POSEIDON Groups 3 and 4 were included. POSEIDON Group-3 comprised women aged <35 years with AMH <1.2 ng/mL (n = 547), and Group-4 comprised women aged ≥35 years with AMH <1.2 ng/mL (n = 703). All comparative analyses and outcome assessments were performed exclusively between POSEIDON Groups 3 and 4. Participants/materials, setting, methods All autologous IVF cycles in POSEIDON Groups 3 and 4 with extended embryo culture and without PGT were included. Laboratory KPIs—including cycle cancellation, blastulation rate, and embryo utilisation—were analysed to assess progression to embryo transfer. Pregnancy and live birth outcomes were evaluated only in cycles reaching transfer. All women underwent frozen embryo transfer of two good-quality blastocysts. Comparative assessments between Groups 3 and 4 used unadjusted odds ratios. Main results and the role of chance POSEIDON Group-3 demonstrated consistently more favourable laboratory performance and reproductive efficiency compared with Group-4. Cycle-cancellation prior to embryo transfer was significantly lower in Group-3 than Group-4(6%vs10%), corresponding to a reduced likelihood of cycle-cancellation before transfer in Group-3 (unadjusted OR 0.57, 95% CI 0.40–0.81). Blastocyst-conversion was significantly higher in Group-3(63%) compared with Group-4(43%), translating into more than a two-fold higher likelihood of blastocyst formation (unadjusted OR 2.24, 95%-CI 2.01–2.49), indicating superior upstream laboratory progression despite similarly reduced ovarian reserve. This laboratory advantage increased the probability of reaching embryo transfer; however, its translation into reproductive outcomes was incomplete. Implantation rates per embryo transferred were higher in Group-3 than Group-4 (49% vs 32%), corresponding to a modest but statistically signi","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"273 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L26/P-399 A selective JAK1/JAK2 inhibitor, ruxolitinib, increases follicle retention, including primordial follicle, after exposure to cyclophosphamide in xenografted human ovarian tissue","authors":"L. Man, G. Montes de Oca, Z. Rosenwaks, D. James","doi":"10.1093/humrep/deag083.733","DOIUrl":"https://doi.org/10.1093/humrep/deag083.733","url":null,"abstract":"Study question Can systemic Ruxolitinib (Ruxo) treatment increase the retention of primordial follicles (PrFs) after cyclophosphamide (Cp) exposure in a human ovarian tissue xenograft model? Summary answer Administration of Ruxo before Cp exposure increases follicle viability and retention of PrFs in xenografted human ovarian tissue. What is known already Gonadotoxicity, manifesting as a reduction in PrFs, is a well-known side effect of Cp treatment. Current fertility preservation efforts focus primarily on banking oocytes, embryos, or ovarian tissue, as effective strategies to safeguard ovarian reserve in situ remain elusive. We have previously linked inflammatory signaling within the mouse ovary to Cp exposure and shown that pretreatment with Ruxo before Cp administration increased retention of PrFs. Building on these results, we utilized this treatment protocol to test the fertoprotective effect of Ruxo in human ovarian cortical fragments from four different organ donors xenografted into immunocompromised mice. Study design, size, duration We thawed four fragments (∼24x4x1 mm) of human ovarian tissue, each from an organ donor aged 21-28 years. Each strip was divided into six equal pieces, and tissue was evenly distributed among the experimental groups. Mice underwent ovariectomy and co-transplantation of ovarian tissue with endothelial cells (n = 24 grafts bilaterally in 12 NSG mice). Two weeks transplant, mice harboring xenografts representing an equal distribution of donors were treated for 15 days before graft recovery. Participants/materials, setting, methods Mice were divided into three groups for daily intraperitoneal injections. Control (DMSO 14%, daily); Cp (60 mg/kg once a week, with daily DMSO 14%); and Ruxo (100 mg/kg daily) -Cp (60 mg/kg once a week). Two weeks following the first Cp injection, grafts were harvested, fixed in 4% paraformaldehyde, and underwent histologic evaluation with H&E staining and light microscopy imaging. Serum from xenograft-bearing mice was tested for estradiol, progesterone, and AMH levels. Main results and the role of chance In a histological analysis, follicle counts showed a significantly higher (p = 0.03) ratio of PrFs to growing (primary + secondary) follicles in Ruxo-Cp (0.18) versus Cp (0.00) groups. To account for interpatient variability, we calculated the percentage of viable follicles derived from each condition relative to the entire count from each patient tissue fragment; this calculation was performed for all four donors for each follicle type. When comparing PrF percentage, the Ruxo-Cp group exhibited a significantly higher (p = 0.03) median retention rate (14.29%) compared to Cp (0.00%). The retention rate in the Ruxo-Cp group was not significantly different from the CTRL group. Comparing the percentage of total (PrF + growing) follicles, the Ruxo-Cp group (16.35%) had a higher (p = 0.007) median percentage than the Cp group (4.17%). The CTRL group median percentage (16.00%) was also ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"25 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L26/P-026 Single-cell profiling reveals aberrant germ-cell expression as predictor of TESE failure and identifies targets for regenerative interventions in NOA testes","authors":"A. Guzmán-Jiménez, S. González-Muñóz, I. Higueras-Serrano, A. Robles-Fernández, M. Cerván-Martín, M. Molina, M.C. Gonzalvo, M.L. García-Peña, V. Maldonado, A. Espuch, J.A. Castilla, A. Clavero, C. Domínguez-Conde, F.D. Carmona, L. Bossini-Castillo","doi":"10.1093/humrep/deag083.362","DOIUrl":"https://doi.org/10.1093/humrep/deag083.362","url":null,"abstract":"Study question Can comprehensive single-cell characterisation of germ cells identify molecular predictors of testicular sperm extraction (TESE) outcome and therapeutic targets in patients with non-obstructive azoospermia (NOA)? Summary answer Late-stage germ-cell maturation defects distinguish TESE outcomes, while spermatogonial heterogeneity highlights germ-cell niche restoration as therapeutic strategy. What is known already TESE success varies markedly across NOA histological subtypes, yet molecular predictors distinguishing successful from failed sperm retrieval remain elusive. Previous single-cell studies have characterised germ-cell populations in healthy testes but were limited by small sample sizes and insufficient representation of NOA phenotypes. Spermatogonial stem cell (SSC) heterogeneity and stage-specific markers predictive of sperm retrieval success have not been comprehensively mapped. Emerging evidence suggests growth factor-based therapies may support germ-cell viability and differentiation in vitro; however, their clinical translation requires an improved understanding which germ-cell states are the finest targets to regenerative interventions in NOA patients. Study design, size, duration Single-cell RNA sequencing (scRNA-seq) was performed on testicular biopsies from fourteen NOA patients stratified according to TESE outcome. All samples were collected and cryopreserved as single-cell suspensions at the time of testicular biopsy for assisted reproductive technologies. Germ-cell proportions and transcriptional profiles were compared between patient with successful (TESE+) and unsuccessful (TESE-) sperm retrieval to identify specific cell clusters and differentially expressed genes in each condition and germ-cell stages. Participants/materials, setting, methods Patients were comprehensively classified with embryologist support into TESE + (n = 3) or TESE- (n = 11). scRNA-seq libraries were generated using 10x Genomics Next GEM technology, followed by stringent quality control filtering. Over 20,000 germ-cell transcriptomes were retained and annotated using automated and manual approaches based on established markers such as UTF1, MAGEA4, HORMAD1 or PRM1. Trajectory inference and differential expression analyses were performed using Scanpy. Main results and the role of chance We initially defined 20 subclusters encompassing all germ-cell types. High-resolution single-cell profiling revealed previously unappreciated SSC heterogeneity, resolving four transcriptionally distinct populations arranged along a differentiation continuum. A primitive SSC subset characterised by high expression of GFRA1, FGFR2, and ICA1L was positioned at the root of the spermatogenic lineage by trajectory analysis, likely representing an early stem-cell pool. Additionally, late-stage germ cells exhibited TESE outcome-associated molecular signatures. Elongated spermatids from TESE- samples showed significantly increased mitochondrial gene expression, where","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L26/P-171 Associations between artificial intelligence (AI)-based oocyte imaging scores and subsequent embryo AI scores assessed using KIDScore D5, iDAScore and CHLOE-EQ: a retrospective study","authors":"Z. Yarkiner, Z. Atayurt, G. Raad, G. Liperis, Y. Yilancilar, O. Ammar, B. Yuksel, M. Serdarogullari","doi":"10.1093/humrep/deag083.507","DOIUrl":"https://doi.org/10.1093/humrep/deag083.507","url":null,"abstract":"Study question Is an AI-based oocyte imaging score associated with embryo AI scores following fertilisation generated by multiple AI platforms? Summary answer Higher AI-based oocyte scores were associated with significantly higher downstream embryo AI scores across multiple platforms. What is known already Several AI systems are integrated into early embryo assessment. KIDScore assesses implantation potential based on morphokinetics, CHLOE-EQ analyses time-lapse imaging to generate an AI-based embryo viability score, and iDAScore produces a score associated with implantation likelihood. However, these models are applied at the embryo stage, limiting their utility for expectation management in oocyte cryopreservation patients and early counselling on cycle prognosis. MAGENTA is a non-invasive AI tool that assigns a 0–10 score to metaphase II oocytes, with higher scores indicating greater blastocyst potential. Whether MAGENTA scores are associated with downstream embryo AI scores across platforms remains unknown. Study design, size, duration This retrospective, single-centre study analysed 2,341 fresh metaphase II oocytes from intracytoplasmic sperm injection (ICSI) cycles performed between March 2024 and December 2025. Only fresh semen samples were included; samples with concentration <5 million/ml and motility <10% were excluded. The primary variable was the AI-based oocyte imaging score (MAGENTA), compared with embryo AI scores generated by iDAScore, KIDScore D5 and CHLOE-EQ. Participants/materials, setting, methods Oocyte images were captured prior to ICSI and scored using MAGENTA, with oocytes categorised as A (7.6–10.0; high), B (5.1–7.5; medium–high), C (2.6–5.0; low–medium), or D (0.0–2.5; low). Injected oocytes were cultured until Day 5 in an EmbryoScope+. Embryo AI scores were generated using iDAScore (v1.2.0), KIDScore D5 (v.3) based on morphokinetic annotation, and CHLOE-EQ derived from time-lapse recordings. Main results and the role of chance The mean age of women was 28.54±5.73 years. For KIDScore D5, embryos from low-quality oocytes (MAGENTA group D) had a 22% lower score than those from high-quality oocytes (group A) (Exp(B)=0.78, 95% CI 0.70–0.86; p < 0.001). Embryos from medium–high-quality oocytes (group C) had a 9% lower KIDScore D5 than group A (Exp(B)=0.91, 95% CI 0.84–0.99; p = 0.026). For iDAScore, embryos from group D had a 27% lower score than group A (Exp(B)=0.73, 95% CI 0.65–0.82; p < 0.001), while embryos from group C had a 10% lower score (Exp(B)=0.90, 95% CI 0.81–0.99; p = 0.032). For CHLOE-EQ, embryos from group D showed a 27% lower score than group A (Exp(B)=0.73, 95% CI 0.63–0.86; p < 0.001), while embryos from group C had a 12% lower score (Exp(B)=0.88, 95% CI 0.77–0.99; p = 0.036). Oocytes in MAGENTA group B did not differ from group A for any embryo AI score (all p > 0.40). Limitations, reasons for caution This was a retrospective, single-centre study, limiting causal i","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}