Emad Babakhanzadeh, Ali Khodadadian, Majid Nazari, Mahya Mozhdeh, Serajoddin Vahidi Mehrgardi, Mohammad Hassan Jafari, Mohammadreza Dehghani, Soudeh Ghafouri-Fard, Nasrin Ghasemi
{"title":"Circular RNA-Mediated ceRNA networks predict sperm retrieval outcomes in non-obstructive azoospermia.","authors":"Emad Babakhanzadeh, Ali Khodadadian, Majid Nazari, Mahya Mozhdeh, Serajoddin Vahidi Mehrgardi, Mohammad Hassan Jafari, Mohammadreza Dehghani, Soudeh Ghafouri-Fard, Nasrin Ghasemi","doi":"10.1007/s10815-026-04013-x","DOIUrl":"https://doi.org/10.1007/s10815-026-04013-x","url":null,"abstract":"<p><strong>Introduction: </strong>Non-obstructive azoospermia (NOA) is a severe form of male infertility in which focal spermatogenesis may persist in otherwise functionally impaired testes. Testicular sperm extraction by microdissection (mTESE) remains the standard procedure for sperm retrieval, but its unpredictable success rate emphasizes the urgent need for reliable, non-invasive biomarkers to support clinical decision-making. Recent advances in transcriptomics have highlighted the role of circular RNAs (circRNAs), microRNAs (miRNAs), and their mRNA targets in the formation of competing endogenous RNA networks (ceRNAs) that regulate spermatogenesis.</p><p><strong>Methods: </strong>In this study, we identified and validated two novel ceRNA axes, circSH3PXD2A/miR-375-3p/SH3PXD2A and hsa_circ_0037070/miR-487b-3p/ALDH1A3, by integrative bioinformatics and experimental analyses.</p><p><strong>Results: </strong>Both SH3PXD2A and ALDH1A3 were significantly upregulated in NOA patients, while their regulatory miRNAs were downregulated, with circRNA partners showing subtype-specific changes. Importantly, the differences in expression correlated with the mTESE results: NOA - patients (failed recovery) showed more extreme dysregulation than NOA + . Receiver operating characteristic (ROC) curve analysis confirmed the diagnostic potential of these markers, with circRNAs and miRNAs showing high discriminatory power (AUC > 0.90).</p><p><strong>Conclusion: </strong>Our results demonstrate that dysregulation of circRNA-miRNA-mRNA networks is a key feature of NOA and that circulating circRNAs and miRNAs can serve as minimally invasive biomarkers for predicting sperm retrieval success. These findings not only improve our understanding of the molecular basis of NOA, but also open up new avenues for precision diagnostics in male infertility.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Gan, Shu-Han Yang, Yan Shi, Yu Zhang, Wen-Bo Lian, Jia-Xin Shi, Chen Zhang, Xuan Zhang, Jian Wang
{"title":"FXYD1 dysregulation impairs trophoblast function via a miR-486-3p-regulated axis in recurrent miscarriage.","authors":"Jie Gan, Shu-Han Yang, Yan Shi, Yu Zhang, Wen-Bo Lian, Jia-Xin Shi, Chen Zhang, Xuan Zhang, Jian Wang","doi":"10.1007/s10815-026-03999-8","DOIUrl":"https://doi.org/10.1007/s10815-026-03999-8","url":null,"abstract":"<p><strong>Purpose: </strong>Recurrent miscarriage (RM) is a prevalent pregnancy complication with incompletely understood molecular mechanisms. Our prior work identified FXYD1 as a hub gene dysregulated in RM and its involvement in decidualization. Thus, this study aimed to characterize the functional role of FXYD1 in trophoblast biology and investigate a FXYD1-centered regulatory axis.</p><p><strong>Methods: </strong>The expression levels of FXYD1 and miR-486-3p were evaluated in placental villous tissues from RM patients and gestational age-matched healthy controls. The HTR-8/SVneo cells, an immortalized human first-trimester extravillous trophoblast cell line, was utilized to assess the proliferation, migration and invasion capacities via CCK-8, wound healing, and Transwell assays, respectively. RNA sequencing was performed to characterize transcriptomic changes induced by FXYD1 overexpression.</p><p><strong>Results: </strong>The villous FXYD1 expression was significantly increased in RM patients. Functional assays revealed that FXYD1 overexpression impaired the proliferation, migration, and invasion capacities of HTR-8/SVneo cells. Subsequently, miR-486-3p was identified as an upstream regulator of FXYD1, and miR-486-3p overexpression partially rescued FXYD1-mediated suppression of those trophoblast functional phenotypes. Transcriptomic profiling following FXYD1 overexpression uncovered extensive differentially expressed genes, and gene set enrichment analysis (GSEA) indicated significant enrichment in signaling pathways, including Wnt, Hippo, Notch, and TGF-β signaling pathways, which are implicated in trophoblast regulation.</p><p><strong>Conclusions: </strong>Collectively, this study preliminarily revealed FXYD1 serves as a potential regulator of trophoblast function and identifies the miR-486-3p/FXYD1 axis as a candidate molecular mechanism associated with trophoblast dysfunction. These findings provide new insights into the molecular mechanisms of RM and highlight possible directions for future therapeutic exploration.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michelle Bayefsky, Jensen Reckhow, Erkan Buyuk, Anate Brauer, Joseph Lee, Alan B Copperman, Phillip Romanski
{"title":"Physician views on ethically challenging clinical scenarios: a society for reproductive endocrinology and infertility member survey.","authors":"Michelle Bayefsky, Jensen Reckhow, Erkan Buyuk, Anate Brauer, Joseph Lee, Alan B Copperman, Phillip Romanski","doi":"10.1007/s10815-026-04009-7","DOIUrl":"https://doi.org/10.1007/s10815-026-04009-7","url":null,"abstract":"<p><strong>Purpose: </strong>The goal of this study was to examine Reproductive Endocrinology and Infertility (REI) physicians' views regarding ethically challenging clinical scenarios.</p><p><strong>Methods: </strong>This national, cross-sectional survey study was administered to members of the Society for Reproductive Endocrinology and Infertility (SREI). The survey consisted of nine scenarios and six demographic questions. Topics included: using a gestational carrier without a medical indication, transferring multiple embryos into a gestational carrier, selecting embryo sex, using preimplantation genetic testing for polygenic conditions (PGT-P), and offering futile care.</p><p><strong>Results: </strong>154 REI physicians completed the survey (response rate ~ 20%). A large majority of respondents (88.3%) reported discomfort with transferring more than one embryo into a gestational carrier, and 59.7% reported discomfort with using a gestational carrier without a medical indication. About half of participants (52.6%) reported comfort with performing in vitro fertilization (IVF) solely for sex selection. Most respondents reported discomfort with the use of PGT-P for medical conditions (74.0%) and non-medical traits (89.6%). In contrast, 57.8% of participants reported comfort with performing IVF perceived to be futile, most commonly citing that it could provide psychological benefit and facilitate the transition to an alternative family building option, such as oocyte donation or adoption. Higher mean comfort scores across all scenarios were associated with working at a private practice (p = 0.003) and male gender (p = 0.004).</p><p><strong>Conclusion: </strong>Results from this survey provide insight into clinicians' views on ethically challenging scenarios and can inform the development of policies at the clinic and professional society levels that promote respectful and responsible patient care.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Not all abnormal fertilization is equal: occurrence, developmental competence, and ploidy outcomes of 1PN, 3PN, and 2.1PN zygotes in ICSI/PGT-A cycles.","authors":"Marzia Barberi, Giulia Pirastu, Ilaria Listorti, Alessandra Ruberti, Alessandro Colasante, Daniele Paccagnini, Claudia Nucera, Anil Biricik, Maria Teresa Varricchio, Ermanno Greco, Pierfrancesco Greco","doi":"10.1007/s10815-026-04000-2","DOIUrl":"https://doi.org/10.1007/s10815-026-04000-2","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize the occurrence, developmental competence, and ploidy outcomes of abnormally fertilized oocyte (AFO) subtypes in ICSI/PGT-A cycles, and to assess whether maternal age independently predicts abnormal fertilization.</p><p><strong>Methods: </strong>Prospective observational study including 1033 ICSI/PGT-A cycles (6373 inseminated oocytes). AFO occurrence was analyzed by binomial logistic regression and multivariable analysis. In 664 time-lapse cycles, pronuclear status was reassessed at 22-24 hpi (Check II) after routine evaluation at 16-18 hpi (Check I). Ploidy analysis was performed on 78 AFO-derived blastocysts by SNP genotyping using NGS technology.</p><p><strong>Results: </strong>AFOs accounted for 6.8% of inseminated oocytes (1PN 3.1%, 3PN 2.1%, 2.1PN 1.2%, > 3PN 0.4%). Maternal age was the only independent predictor (OR 1.04/year; p < 0.05), mainly for 3PN and 2.1PN. Blastocyst development differed across categories (1PN 11.1%, 3PN 25.7%, 2.1PN 40.5% vs. 2PN 54.4% p < 0.05), and 1PN and 2.1PN were mainly diploid (71.4% and 88.9% respectively), though both were lower than 2PN (99.9%; p < 0.001), while 3PN were mostly triploid (73.3%). The rate of blastocysts suitable for transfer calculated per zygote was 1PN 2.0%, 3PN 0.8%, and 2.1PN 8.1%, markedly lower than 2PN (22.5%; p < 0.001). Pronuclear status could change after the standard assessment window: 26% of 2.1PN-derived blastocysts were initially classified as 2PN, suggesting that single-timepoint assessment may misclassify fertilization.</p><p><strong>Conclusions: </strong>AFO subtypes differed in clinical potential according to their developmental competence and ploidy status. Time-lapse monitoring further indicated that some AFOs may be misclassified in a single static pronuclear assessment. Therefore, both ploidy assessment and PGT-A should be considered before the clinical use of AFO-derived embryos.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148793675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amaxsell Thiago Barros de Souza, Marcela Queiroz Lopes de Melo Martins, Juliana Dantas de Araújo Santos Camargo, Ricardo Ney Cobucci, Ana Katherine Gonçalves, Viviane Souza do Amaral
{"title":"Long non-coding RNA gene polymorphisms and risk of recurrent pregnancy loss: a meta-analysis.","authors":"Amaxsell Thiago Barros de Souza, Marcela Queiroz Lopes de Melo Martins, Juliana Dantas de Araújo Santos Camargo, Ricardo Ney Cobucci, Ana Katherine Gonçalves, Viviane Souza do Amaral","doi":"10.1007/s10815-026-03996-x","DOIUrl":"https://doi.org/10.1007/s10815-026-03996-x","url":null,"abstract":"<p><strong>Purpose: </strong>Long non-coding RNAs (lncRNAs) are key regulators of transcriptional, epigenetic, and post-transcriptional processes involved in implantation, trophoblast function, and early placental development. Genetic polymorphisms within lncRNA loci may alter their expression or regulatory activity, potentially contributing to recurrent pregnancy loss (RPL). We aimed to evaluate the association between lncRNA gene polymorphisms and susceptibility to RPL.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted according to PRISMA and MOOSE guidelines and prospectively registered in PROSPERO (CRD420261298804). A systematic search was performed in PubMed, Embase, Scopus, and Web of Science from database inception to January 2026, without language or date restrictions. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-E. Meta-analyses were performed using fixed- or random-effects models according to heterogeneity. Hardy-Weinberg equilibrium testing, sensitivity analyses, subgroup analyses by ancestry, and certainty of evidence assessment using the GRADE framework were conducted.</p><p><strong>Results: </strong>Sixteen case-control studies involving 11,088 participants were included, comprising 5169 women with RPL and 6454 controls. Eight polymorphisms across four lncRNA genes were quantitatively synthesized. Significant associations with increased RPL susceptibility were observed for HOTAIR rs4759314 (AG vs AA: OR, 2.75 [95% CI, 2.04-3.71]; GG vs AA: OR, 2.16 [95% CI, 1.09-4.26]; G vs A: OR, 2.06 [95% CI, 1.48-2.88]) and HOTAIR rs920778 (CC vs TT: OR, 2.00 [95% CI, 1.28-3.11]; TC + CC vs TT: OR, 1.39 [95% CI, 1.09-1.76]; C vs T: OR, 1.38 [95% CI, 1.14-1.66]). A protective association was consistently identified for HOTTIP rs1859168 (CA vs AA: OR, 0.63 [95% CI, 0.45-0.89]; CC vs AA: OR, 0.33 [95% CI, 0.17-0.67]; C vs A: OR, 0.61 [95% CI, 0.45-0.82]). Sensitivity analysis further strengthened the evidence for HOTAIR rs1899663, with significant associations emerging for TT vs GG (OR, 2.59 [95% CI, 1.46-4.61]) and T vs G (OR, 1.41 [95% CI, 1.15-1.72]). Overall certainty of evidence for all pooled outcomes was rated as very low.</p><p><strong>Conclusion: </strong>This meta-analysis provides the first quantitative evidence that inherited variation within lncRNA loci may contribute to susceptibility to RPL. Variants in HOTAIR, particularly rs4759314 and rs920778, were associated with increased RPL risk, whereas HOTTIP rs1859168 showed a protective association. However, the certainty of evidence remains very low, and these findings should be interpreted cautiously until confirmed by large, well-designed, multi-ancestry studies with functional validation.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148766553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mohammed El Amine Bechar, Jean-Marie Guyader, Marwa Elbouz, Frédéric Morel, Aurore Perrin, Nesma Settouti
{"title":"From time-lapse to morphokinetics: neural ODE dynamics for reliable embryo stage transition timing.","authors":"Mohammed El Amine Bechar, Jean-Marie Guyader, Marwa Elbouz, Frédéric Morel, Aurore Perrin, Nesma Settouti","doi":"10.1007/s10815-026-03960-9","DOIUrl":"https://doi.org/10.1007/s10815-026-03960-9","url":null,"abstract":"<p><strong>Problem: </strong>Time-lapse imaging (TLI) enables longitudinal and non-invasive embryo monitoring in IVF, yet morphokinetic annotation remains labor-intensive and subject to inter-operator variability. Automated detection of developmental phase transitions is challenging due to subtle morphological changes, heterogeneous acquisition conditions, discrete and potentially irregular image sampling, focal-plane variability, and the need for temporally consistent predictions.</p><p><strong>Aim: </strong>We aim to detect morphokinetic phase transitions in embryo TLI videos using a robust, clinically oriented framework designed to support human-in-the-loop annotation rather than replace clinical decision-making or commercial embryo selection systems.</p><p><strong>Methods: </strong>We propose a spatio-temporal Neural Ordinary Differential Equation (Neural ODE) model for continuous-time latent representation learning between discretely acquired observations, coupled with a reference-based transition scoring mechanism and an online, one-class detection strategy. The method, named Reference-Based Neural ODE Change Detector (RB-NODE), is transition-agnostic and detects when the evolving latent state deviates from a prototype representation of the current developmental phase. Experiments are conducted on the public dataset of Gomez et al., a single-center TLI benchmark comprising 704 embryo videos acquired across seven focal planes. All reported results are computed over the union of test samples generated from the seven focal-plane views, with strict embryo-level data splitting to prevent leakage across focal planes.</p><p><strong>Results: </strong>RB-NODE achieves an AUC of 0.988, an F1@frame of 0.975, a Det@5f of 0.873, a Det@10f of 0.956, and a mean absolute localization error of 2.64 frames. Although a ResNet18+LSTM baseline obtains a marginally higher Det@5f, RB-NODE provides the best AUC, F1@frame, Det@10f, and mean temporal error among the evaluated methods. Event-group analysis shows particularly strong performance on morula/blastocyst-related transitions, with Det@5f = 0.910, Det@10f = 0.978, and a mean temporal error of 1.90 frames. RB-NODE also remains compatible with online use, processing frames at approximately 171 FPS on an NVIDIA RTX 6000 Ada Generation GPU.</p><p><strong>Conclusion: </strong>Continuous-time spatio-temporal modeling with Neural ODEs provides a promising and reproducible approach for robust morphokinetic transition detection in embryo TLI, offering practical support for standardized annotation workflows. The proposed framework is intended as an annotation-support tool, not as an autonomous embryo selection system. External validation across multiple IVF centers, TLI platforms, acquisition intervals, annotation protocols, and focal-plane configurations remains necessary before clinical deployment.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fulin Liu, Qing Zhou, Yuwei Chenzhang, Xueming Ju, Bo He, Rui Huang, Chao Li, Fangyuan Luo, Jiyun Yang
{"title":"Longitudinal clinical impact of dynamic variant re-classification on reproductive decision-making: a 3-year case study.","authors":"Fulin Liu, Qing Zhou, Yuwei Chenzhang, Xueming Ju, Bo He, Rui Huang, Chao Li, Fangyuan Luo, Jiyun Yang","doi":"10.1007/s10815-026-03997-w","DOIUrl":"https://doi.org/10.1007/s10815-026-03997-w","url":null,"abstract":"<p><strong>Purpose: </strong>The clinical application of sequencing guidelines often yields variants of uncertain significance (VUS), creating profound challenges in prenatal genetic counseling. This study demonstrates the clinical utility and real-world impact of dynamic, longitudinal variant re-classification on reproductive decision-making in a family affected by an atypical SEC24D-associated skeletal phenotype.</p><p><strong>Methods: </strong>Over a 3-year period (2023-2026), a multidisciplinary diagnostic workflow was employed, integrating trio whole-exome sequencing, protein structural modeling, prenatal ultrasound, fetal magnetic resonance imaging, post-mortem histopathology, and preimplantation genetic testing for monogenic disorders (PGT-M). Variant pathogenicity was sequentially curated according to the American College of Medical Genetics and Genomics (ACMG) framework.</p><p><strong>Results: </strong>A homozygous SEC24D variant (c.1942G > C, p.Gly648Arg) was identified in a proband presenting with isolated craniofacial ossification defects without classic long-bone fractures. Over 3 years, the variant was dynamically re-classified from VUS to likely pathogenic (LP), back to VUS, and to LP again, driven by institutional peer-review debates regarding the conservative application of computational structural criteria versus clinical intuition. This diagnostic instability directly dictated a cascade of critical reproductive events: the termination of a second pregnancy demonstrating recurrent fetal cranial defects confirmed by amniocentesis and post-mortem examination, followed by the deployment of PGT-M within a diagnostic \"gray zone.\" Ultimately, the successful delivery of a healthy, non-carrier infant in June 2026 provided crucial family co-segregation data, successfully resolving the classification loop and securing a definitive likely pathogenic status.</p><p><strong>Conclusions: </strong>Diagnostic uncertainty in prenatal genomics is a persistent clinical reality rather than a transient evidence gap. Longitudinal variant reinterpretation combined with transparent shared decision-making is vital to safely navigate borderline classifications and optimize reproductive trajectories.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Craig, Laura Wartschinski, Mathew Eyre, Ivan Davidson, Michael Christensen, Tobias Wolfram
{"title":"Stage-structured, distributional prediction of IVF outcomes with conditional updating.","authors":"Alexander Craig, Laura Wartschinski, Mathew Eyre, Ivan Davidson, Michael Christensen, Tobias Wolfram","doi":"10.1007/s10815-026-03933-y","DOIUrl":"https://doi.org/10.1007/s10815-026-03933-y","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a stage-structured, distribution-based prediction framework for in vitro fertilization (IVF) that generates full probability distributions at each treatment stage and enables conditional updating of downstream predictions when observed outcomes become known.</p><p><strong>Methods: </strong>We conducted an observational modeling study using de-identified UK Human Fertilisation and Embryology Authority (HFEA) registry data (2017-2018; up to 101,217 model-ready cycles after stage-specific filtering) to model egg retrieval, maturation, and fertilization. Egg retrieval was modeled using a zero-inflated negative binomial specification. Downstream transitions such as blastocyst formation, euploidy, vitrification survival, and live birth after euploid transfer were modeled using stage-specific logistic regressions calibrated to published cohorts and national registry summaries (429,507 additional observations). Predictive performance of HFEA-derived models was evaluated on held-out HFEA test sets using point-prediction accuracy, train-test gaps, prediction-interval coverage, and calibration across predicted outcome strata.</p><p><strong>Results: </strong>The framework propagates full probability distributions across sequential IVF stages rather than point estimates. Held-out HFEA validation showed minimal train-test degradation ( <math><msup><mi>R</mi> <mn>2</mn></msup> </math> gaps under 0.007), with modest expected-count accuracy for egg retrieval and stronger expected-count accuracy for maturity and fertilization. Egg-retrieval prediction intervals showed near-nominal coverage (50%: 50.2%; 80%: 79.2%; 95%: 94.9%), and observed mean outcomes were close to predicted means across predicted-yield/rate strata. When observed stage outcomes were entered, downstream distributions updated appropriately, reducing uncertainty and preserving cycle-specific biological parameters in both single- and multi-cycle scenarios.</p><p><strong>Conclusion(s): </strong>A sequential, distribution-based IVF prediction model with conditional updating provides uncertainty-quantified, stage-aware predictions that dynamically adapt to patient-specific outcomes, supporting more individualized counseling and treatment planning.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"ICSI media buffers: is there room for improvement?","authors":"Gerard Campos, Liesl Nel-Themaat","doi":"10.1007/s10815-026-03994-z","DOIUrl":"https://doi.org/10.1007/s10815-026-03994-z","url":null,"abstract":"<p><p>Maintaining physiological extracellular pH (pHe) is essential for oocyte viability and embryonic development, particularly during ICSI, when metaphase II oocytes have their intracellular pH (pHi) regulation mechanisms temporarily inactivated. HEPES- and MOPS-buffered handling media are routinely used in IVF laboratories, with decades of clinical use supporting their effectiveness and safety. Although concerns regarding their biological effects beyond pH buffering have occasionally emerged, most are derived from experimental settings and are not representative of clinical IVF procedures, more likely influenced by experimental conditions and media composition rather than by the zwitterions themselves. Nevertheless, while evidence from human oocytes remains extremely limited and preliminary, the improved embryological outcomes and transcriptomic profiles recently reported from bicarbonate-buffered handling media have renewed interest in exploring more physiological ICSI media formulations. While current evidence remains far from conclusive and insufficient to support immediate changes in clinical practice, emerging findings suggest that routine systems may not yet be fully optimized and could represent an opportunity for further improvement. Future evaluation of bicarbonate-buffered media for ICSI should include robust standardization of pH measurement methodologies together with optimization of handling conditions, including oil and dish characteristics, that influence pHe stability.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luce A Kassi, Sanjana Konda, Joyce Ou, Julia McAdams, Robin Cram, May-Tal Sauerbrun-Cutler, Kathryn Grive
{"title":"Endometriosis and ovarian aging: a pilot study exploring oxidative stress and DNA damage markers.","authors":"Luce A Kassi, Sanjana Konda, Joyce Ou, Julia McAdams, Robin Cram, May-Tal Sauerbrun-Cutler, Kathryn Grive","doi":"10.1007/s10815-026-03990-3","DOIUrl":"https://doi.org/10.1007/s10815-026-03990-3","url":null,"abstract":"<p><strong>Purpose: </strong>To assess whether specific markers of oxidative stress and DNA damage are expressed at higher levels in primordial follicles of patients with endometriomas compared to age-matched controls.</p><p><strong>Methods: </strong>A retrospective pilot cohort study was conducted using ovarian tissue from patients who underwent unilateral or bilateral salpingo-oophorectomy for symptomatic endometriomas, with controls undergoing an identical procedure for other benign gynecologic conditions. Immunohistochemistry (IHC) was used to assess percent positivity in primordial follicles for 4-hydroxy-2-nonenal (4-HNE) as a marker of oxidative stress; 8-Oxoguanine (8-Oxo) and phosphorylated H2AX (γH2AX) for DNA damage. Chi-square tests were used for categorical variables and Student t-tests for continuous variables, with p < 0.05 considered significant.</p><p><strong>Results: </strong>Twenty-nine patients were included (8 controls, 21 with endometriomas). Age (39.4 ± 5.1 vs. 37.1 ± 4.6 years, p = 0.269), BMI (33.6 ± 10.6 vs. 29.5 ± 7.8 kg/m<sup>2</sup>, p = 0.310) were similar between groups. Racial distribution, nulliparity, hormonal therapy use, and smoking status were also comparable. The average endometrioma size was 6.6 ± 2.8 cm. All molecular markers showed higher percent positivity in the endometrioma group compared to the control group. γH2AX demonstrated a statistically significant increase (63.6% vs. 50.1%, p = 0.033). 8-Oxo (67.5% vs. 55.8%, p = 0.070) and 4-HNE (65.1% vs. 61.8%, p = 0.168) were also elevated in the endometrioma group but did not reach statistical significance.</p><p><strong>Conclusion: </strong>Patients with endometriomas demonstrated increased follicular DNA damage, with elevated γH2AX expression, supporting the notion that endometriomas may impair follicular quality through DNA damage mechanisms.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148712398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}