Journal of Assisted Reproduction and Genetics最新文献

{"title":"Sharing new genetic risk information with recipients of donor gametes.","authors":"Dorian Accoe, Guido Pennings, Sandra Janssens, Frauke Vanden Meerschaut, Kelly Tilleman, Heidi Mertes","doi":"10.1007/s10815-026-04059-x","DOIUrl":"https://doi.org/10.1007/s10815-026-04059-x","url":null,"abstract":"","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224236","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":"X-linked novel hemizygous ADGRG2 variants associated with male factor infertility.","authors":"Yuwei Yuan, Yong Li, Wenqing Lu, Zhendong Peng, Lei Deng, Xinle Lin, Lin Liu, Lanlan Meng, Chen Tan, Ge Lin, Qianjun Zhang, Yue-Qiu Tan, Huan Zhang, Wenbin He, Huanzhu Li, Liang Hu, Chaofeng Tu","doi":"10.1007/s10815-026-04062-2","DOIUrl":"https://doi.org/10.1007/s10815-026-04062-2","url":null,"abstract":"<p><strong>Purpose: </strong>To screen for ADGRG2 gene mutations in CFTR-negative patients with male infertility or congenital bilateral absence of the vas deferens (CBAVD), and to assess the feasibility and outcomes of intracytoplasmic sperm injection (ICSI) for achieving successful pregnancies in this population.</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed in 133 infertile men with obstructive azoospermia (OA). Sanger sequencing were conducted on peripheral blood samples collected from nine patients with ADGRG2 variants. The AlphaFold database and PyMOL software were used to predict the 3D structure of the mutant ADGRG2 protein. In vitro assays were conducted to assess the functional impact of the identified ADGRG2 variants. In addition, we also conducted a retrospective analysis of the clinical assisted reproductive information of these patients.</p><p><strong>Results: </strong>We identified eight ADGRG2 hemizygous pathogenic variants in nine unrelated patients with CBAVD from 133 OA men: one splicing variant (c.1839 + 1G > A), three frameshift variants (c.2956_2957del: p.M986Vfs*2; c.2396dupT: p.L799Ffs*18 and c.895delA: p.I299Ffs*12), two nonsense variants (c.2473C > T: p.R825* and c.2971G > T: p.E991*), and two missense variants (c.510G > C: p.E170D and c.549C > G: p.S183R). All ADGRG2 variants-affected individuals presented with azoospermia or severe oligozoospermia. All of these variants were absent or rare in public databases. 3D protein structure modeling predicted that ADGRG2 variants lead to alterations in the spatial conformation of the protein. In vitro experiments further confirmed that these variants result in the production of truncated proteins or reduced protein levels. Notably, four patients undergoing ICSI treatment achieved successful fertilization and pregnancy.</p><p><strong>Conclusion: </strong>Our findings established ADGRG2 variants cause male infertility and may be the etiology of CBAVD, expanding the associated mutational spectrum and reinforcing the gene's critical role in male fertility, thereby supporting the integration of comprehensive ADGRG2 screening into clinical practice to enhance genetic and reproductive counseling for affected patients.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224190","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":"Selected abstracts from the 14th Congress of Turkish Foundation of Reproductive Medicine: Oral presentations [OP-01-OP-81].","authors":"","doi":"10.1007/s10815-026-04045-3","DOIUrl":"https://doi.org/10.1007/s10815-026-04045-3","url":null,"abstract":"","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224229","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 Day-4 embryos are equal: developmental stage predicts outcomes after single embryo transfer.","authors":"Moran Shapira, Jigal Haas, Adva Aizer, Micha Baum, Ariel Hourvitz, Ettie Maman","doi":"10.1007/s10815-026-04001-1","DOIUrl":"https://doi.org/10.1007/s10815-026-04001-1","url":null,"abstract":"<p><strong>Purpose: </strong>Evaluate outcomes of Day-4 embryo transfer according to embryonic developmental stage.</p><p><strong>Methods: </strong>This retrospective single-center study included fresh IVF/ICSI cycles with day-4 single embryo transfer between January 2021 and July 2025. Cycles with double embryo transfer, rescue ICSI, or missing follow-up were excluded. Transfers were divided into three groups based on embryonic stage at transfer: cleavage, morula or blastocyst-stage. Demographic and cycle characteristics, as well as clinical outcomes, were compared. Clinical pregnancy was the primary outcome.</p><p><strong>Results: </strong>A total of 669 day-4 single fresh embryo transfer cycles were included: 130 cleavage-stage (19.4%), 449 morula-stage (67.1%), and 90 blastocyst-stage (13.5%). Compared to the morula stage, the cleavage-stage group was characterized by an older age, lower oocyte yield and fewer 2PN embryos, while the blastocyst-stage group was characterized by a younger age and a similar oocyte yield and 2PN embryos. Clinical pregnancy rates increased significantly with advancing embryonic stage (10.0%, 32.96%, and 48.89%, respectively; p < 0.05). In multivariable analysis, only increasing maternal age (OR 0.92, 95% CI 0.88-0.96) and cleavage-stage transfer (OR 0.37, 95% CI 0.18-0.78) remained negatively associated with clinical pregnancy.</p><p><strong>Conclusions: </strong>Fresh day 4 embryo transfer outcomes are strongly influenced by embryonic developmental stage. Cleavage-stage embryos on day 4 are associated with poor pregnancy rates and may benefit from extended culture. In contrast, day 4 morula or blastocyst transfer represents a viable clinical option, particularly when logistical constraints preclude day 5 transfer.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215794","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":"Novel heterozygous GMNN variants in human early embryonic arrest involving CHK1‑mediated cell cycle dysregulation.","authors":"Huling Hu, Wei Su, Lianyue Li, Fei Meng, Fei Gong, Han Zhao, Ge Lin, Honghui Zhang, Wei Zheng","doi":"10.1007/s10815-026-04063-1","DOIUrl":"https://doi.org/10.1007/s10815-026-04063-1","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the genetic determinants underlying human early embryonic arrest (EA).</p><p><strong>Methods: </strong>Whole‑exome sequencing was performed to screen for candidate variants, followed by Sanger sequencing for family‑based validation. The effects of identified variants on Geminin subcellular localization were examined via immunofluorescence, while their impact on CHK1 pathway activation and DNA damage was assessed in HEK‑293 cells using western blot. Patient‑derived arrested embryos were also stained for γH2AX to evaluate DNA damage in situ. In addition, transcriptomic profiling was conducted to explore the broader biological consequences of GMNN variants during early human embryogenesis.</p><p><strong>Results: </strong>We identified two heterozygous GMNN variants-c.94 T > C (p.Ser32Pro) and c.601_606del (p.Ser201_Ser202del)-in two families presenting with female infertility due to EA. Functional studies revealed that these variants perturb cell cycle regulation, accompanied by CHK1 activation, elevated DNA damage levels, and altered nuclear distribution of Geminin. Transcriptomic analysis of patient embryos further confirmed substantial disruptions in cell cycle-related pathways and increased DNA damage, consistent with the cellular findings.</p><p><strong>Conclusions: </strong>Our findings expand the mutational and phenotypic spectrum of GMNN‑associated infertility and reinforce its critical role in cell cycle control during preimplantation development. The distinct transcriptomic signatures arising from different GMNN variants provide mechanistic insights into embryo arrest and offer potential molecular diagnostic markers as well as avenues for individualized therapeutic strategies.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216080","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":"Obesity and morbid obesity are associated with reductions in live birth rate and increased miscarriage rate after frozen embryo transfer.","authors":"Patricia Xu, Lauren Tetelbaun, Alexa Setteducate, Mindy Lowy, Eliana Felder, Martin Keltz","doi":"10.1007/s10815-026-04054-2","DOIUrl":"https://doi.org/10.1007/s10815-026-04054-2","url":null,"abstract":"<p><strong>Purpose: </strong>Obesity is associated with poor in-vitro fertilization (IVF) outcomes, with limited data on patients with BMI ≥ 40 kg/m². This study assessed BMI's impact on frozen embryo transfer (FET) outcomes.</p><p><strong>Methods: </strong>A retrospective cohort study (2017-2024) of 1,424 FETs from 889 patients, stratified by BMI: normal (18.5-24.9), overweight (25.0-29.9), obese (30.0-39.9), morbidly obese (≥ 40). Primary outcome was live birth rate per transfer (LBR). Secondary outcomes include clinical intrauterine pregnancy (CIUPR), miscarriage rates (MR), and proportion achieving ≥ 1 live birth. Outcomes were adjusted for age, AMH, FSH, PCOS, tubal infertility, and race.</p><p><strong>Results: </strong>LBR decreased with increasing BMI for all transfers (53.5%, 52.8%, 42.5%, 30.8%, p < 0.001) and single elective euploid transfers (SEETs) (54.2%, 57.8%, 44.5%, 32.3%, p < 0.001). CIUPR showed the same pattern (58.0%, 59.5%, 50.4%, 39.7%; p < 0.001 all transfers; 58.6%, 63.1%, 51.0%, 40.3%; p < 0.001 SEETs), as did the proportion of patients achieving at least one birth (72.9%, 68.3%, 65.8%, 51.1%; p = 0.020). MR significantly increased with BMI (7.4%, 11.2%, 15.2%, 22.6%, p<0.001) for all transfers but not for SEETs (7.5%, 8.4%, 12.8%, 20.0%; p = 0.169). Each one-unit increase in BMI was associated with a 3% reduction in odds of live birth (aOR 0.969, 95% CI 0.951-0.987, p<0.001).</p><p><strong>Conclusion: </strong>Increasing BMI is associated with lower LBR and CIUPR, following FET, including SEETs. MR increased with BMI for all FETs, with a similar but non-significant gradient among SEETs. This highlights the importance of considering BMI when counseling patients, particularly those with morbid obesity.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149194013","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":"Effect of embryo retention on in vitro fertilization outcomes: a retrospective analysis.","authors":"Lucia Maresca, Livia Pellegrini, Cecilia Zanini, Luisa Loiudice, Antonio Pellicer, Mauro Cozzolino","doi":"10.1007/s10815-026-04053-3","DOIUrl":"https://doi.org/10.1007/s10815-026-04053-3","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the incidence of embryo retention (ER) during blastocyst single embryo transfer (SET) cycles and assess its impact on reproductive outcomes in vitro fertilization IVF.</p><p><strong>Methods: </strong>In this retrospective cohort study, 4593 SET cycles from 3061 patients treated at a single IVF center between October 2021 and July 2024 were analyzed. Cycles were categorized according to the occurrence of ER during embryo transfer (ER group, n = 106; control group, n = 4487). Both fresh and frozen transfers using autologous or donor oocytes were included. The primary outcome was live birth rate (LBR). Secondary outcomes included implantation, biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and miscarriage rates. Logistic regression analyses were performed to evaluate associations between ER and reproductive outcomes.</p><p><strong>Results: </strong>ER occurred in 2.3% of SET cycles. Implantation and early pregnancy outcomes were significantly lower in the ER group compared with controls. After adjustment, ER remained significantly associated with lower implantation (aOR 0.84, 95% CI 0.76-0.92; p < 0.001), biochemical pregnancy (aOR 0.49, 95% CI 0.32-0.75; p < 0.001), and clinical pregnancy rates (aOR 0.53, 95% CI 0.34-0.82; p = 0.004). No statistically significant associations were observed for ongoing pregnancy, live birth, or miscarriage.</p><p><strong>Conclusion: </strong>In this cohort, ER during single blastocyst transfer was associated with lower implantation and early pregnancy rates. These findings should nevertheless be interpreted in light of the potential influence of procedural factors associated with embryo transfer. The association between ER and ongoing pregnancy or live birth remains inconclusive.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182035","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":"Could glyoxal be an alternative fixative to paraformaldehyde in human spermatozoa?","authors":"Ferda Topal Celikkan, Ezel Erkan, Fatma Uysal Cinar, Derya Ozdemir Tas, Serhat Hayme, Selda Kahveci, Sinan Ozkavukcu, Alp Can","doi":"10.1007/s10815-026-04060-4","DOIUrl":"https://doi.org/10.1007/s10815-026-04060-4","url":null,"abstract":"<p><strong>Purpose: </strong>Our previous studies demonstrated the superiority of paraformaldehyde (PFA) over glyoxal (Gly) fixation in stem cells, oocytes, and embryos. Here, we compared these two aldehyde-based fixatives in human spermatozoa to determine whether Gly, which is reported to better preserve immunoreactivity, can provide effective and consistent fixation comparable to PFA.</p><p><strong>Methods: </strong>The fixation performance of PFA (3.5%) and Gly (3%), with or without 0.01% Triton-X (TX) permeabilization, was evaluated side-by-side in live and fixed human spermatozoa. Analyses included total protein quantification by Western blotting, epitope detection by super-resolution confocal laser scanning microscopy, ultrastructural assessment by scanning electron microscopy, and DNA fragmentation analysis by TUNEL assay coupled with flow cytometry.</p><p><strong>Results: </strong>Protein fixation assays demonstrated that PFA was superior to Gly in preserving total cellular proteins. Similarly, the sperm-specific membrane protein IZUMO1 was better retained after PFA fixation. In contrast, Gly combined with subsequent TX permeabilization provided superior labeling of nuclear DNA, the acrosomal protein ACRBP, a nuclear DNA-methylating enzyme DNMT3A and TUNEL-based detection of DNA fragmentation compared with all PFA-based fixation conditions. No significant differences between fixatives were observed in ultrastructural preservation, post-fixation live mitochondrial staining.</p><p><strong>Conclusion: </strong>PFA was more effective for preserving total and membrane-associated proteins in human spermatozoa, whereas Gly represented a promising and less toxic alternative for studies targeting nuclear components and DNA-associated molecules. These findings indicate that the choice of fixative should be determined according to the specific cellular targets under investigation, particularly cytoplasmic, membrane-associated, or nuclear proteins and enzymes.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182103","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":"Should PGT-A be routinely utilized for advanced maternal age?","authors":"Alexis Heng Boon Chin, Ido Alon, Ningyu Sun","doi":"10.1007/s10815-026-04049-z","DOIUrl":"https://doi.org/10.1007/s10815-026-04049-z","url":null,"abstract":"<p><p>Preimplantation genetic testing for aneuploidy (PGT-A) is often presented to women of advanced maternal age as a logical safeguard against miscarriage and chromosomal abnormality. Yet intuitive rationale and biological plausibility do not establish net clinical benefit. PGT-A does not improve oocyte or embryo quality; it ranks embryos that already exist. The appropriate objective endpoint is therefore cumulative live birth from an initiated treatment strategy, not implantation after transfer of a selected euploid embryo. Randomized clinical trials, contemporary systematic reviews, meta-analyses, and professional guidance have not shown that routine PGT-A improves cumulative live birth rates in older women, while mosaicism, limitations of trophectoderm sampling, invasive biopsy, variability in laboratory protocols, freeze-thaw requirements, embryo exclusion, financial cost, and treatment delay can impose material harms. These concerns are amplified in older women with fewer transferable blastocysts. Sociocultural anxiety about disability and delayed childbearing, reinforced by commercial promotion, clinical normalization, and misleading risk communication, can further compromise autonomous choice. PGT-A may be utilized selectively for older women, especially when several blastocysts are available and patients prioritize avoiding an aneuploid transfer, but advanced maternal age alone should not convert an uncertain add-on into a routine clinical strategy.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182029","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":"Analysis of the evolving disease burden of female infertility and its associated risk factors.","authors":"Yanchao Lin, Ya Lin","doi":"10.1007/s10815-026-04048-0","DOIUrl":"https://doi.org/10.1007/s10815-026-04048-0","url":null,"abstract":"<p><strong>Background: </strong>The global burden of female infertility is increasing, yet the roles of metabolic syndrome (MetS) and circadian syndrome (CircS) remain poorly understood. This study aimed to describe the global disease burden of female infertility and examine the associations between MetS, CircS, and infertility.</p><p><strong>Methods: </strong>Global Burden of Disease (GBD) 2023 data were used to assess trends in infertility prevalence. Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) were used to evaluate associations between metabolic status and infertility using weighted logistic regression.</p><p><strong>Results: </strong>The global number of women with infertility nearly doubled from 59.8 million in 1990 to 114.5 million in 2023 (ASR, + 25.27%), with the sharpest increase in Western Sub-Saharan Africa (247.6%). Both MetS (OR = 1.41, 95% CI 1.00-1.99) and CircS (OR = 1.46, 95% CI 1.04-2.07) were associated with an elevated risk of infertility. The combined presence of MetS and CircS was also positively associated with infertility (OR = 1.51, 95% CI 1.04-2.18). Among women under 35 years of age, CircS (OR = 1.69; 95% CI 1.00-2.87) and the combination of both syndromes (OR = 1.77; 95% CI 1.02-3.10) were associated with an elevated risk of infertility. Elevated blood pressure was the individual component most strongly associated with infertility.</p><p><strong>Conclusions: </strong>The global burden of female infertility is substantial. Both MetS and CircS are significant risk factors for infertility, with a stronger association for CircS among younger women. Elevated blood pressure showed the strongest association among the individual metabolic components. These findings support integrating metabolic and circadian risk assessment into infertility prevention strategies.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166406","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}