Meiotic and mitotic aneuploidies drive arrest of in vitro fertilized human preimplantation embryos

Genome Medicine, Journal Year: 2023, Volume and Issue: 15(1)

Published: Oct. 2, 2023

Abstract Background The high incidence of aneuploidy in early human development, arising either from errors meiosis or postzygotic mitosis, is the primary cause pregnancy loss, miscarriage, and stillbirth following natural conception as well vitro fertilization (IVF). Preimplantation genetic testing for (PGT-A) has confirmed prevalence meiotic mitotic aneuploidies among blastocyst-stage IVF embryos that are candidates transfer. However, only about half normally fertilized develop to blastocyst stage vitro, while others arrest at cleavage late morula stages. Methods To achieve a more complete view impacts aneuploidy, we applied low-coverage sequencing-based PGT-A large series ( n = 909) arrested trophectoderm biopsies. We then correlated observed with abnormalities first two divisions using time-lapse imaging 843). Results combined was strongly associated morphological grading, proportion ranging 20 90% highest lowest grades, respectively. In contrast, exceptionally (94%), dominated by affecting multiple chromosomes. turn, these were abnormal divisions, such 51% abnormally dividing possessed compared 23% embryos. Conclusions conclude combination drives development increasingly relies on embryonic gene expression stage.

Language: Английский

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Chromosomal, gestational, and neonatal outcomes of embryos classified as a mosaic by preimplantation genetic testing for aneuploidy

Fertility and Sterility, Journal Year: 2023, Volume and Issue: 120(5), P. 957 - 966

Published: July 31, 2023

Language: Английский

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Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles

Reproductive Biology and Endocrinology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 17, 2024

Abstract Background Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, effectiveness of with PGT-A has not been thoroughly investigated. Therefore, this study aims assess association between artificial intelligence (AI)-based (version 1.0) single-embryo transfer (SET) PGT-A. Methods This retrospective was approved by Institutional Review Board Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET ( n = 482) following at a single reproductive center January 2017 June 2021. The blastocyst morphology morphokinetics all embryos were evaluated using time-lapse system. blastocysts ranked based on scores generated iDAScore, which defined as AI scores, or D5 3.2) manufacturer’s protocols. A transferred after examining embryonic ploidy status next-generation sequencing-based platform. Logistic regression analysis generalized estimating equations conducted whether are associated probability live birth (LB) while considering confounding factors. Results revealed score significantly LB (adjusted odds ratio [OR] 2.037, 95% confidence interval [CI]: 1.632–2.542) when pulsatility index (PI) level types chromosomal abnormalities controlled. Blastocysts divided into quartiles accordance their (group 1: 3.0–7.8; group 2: 7.9–8.6; 3: 8.7–8.9; 4: 9.0–9.5). Group 1 had lower rate (34.6% vs. 59.8–72.3%) higher loss (26% 4.7–8.9%) other groups p < 0.05). receiver operating characteristic curve verified significant but limited ability predict (area under [AUC] 0.64); weaker than combination type abnormalities, PI (AUC 0.67). In comparison non-LB groups, both euploid (median: 8.6 8.8) mosaic 8.0 8.6) SETs. Conclusions Although its predictive can be further enhanced, cycles. Euploid low (≤ 7.8) rate, indicating potential annotation-free system decision-support tool deselecting poor

Language: Английский

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In Vitro Culture of Mammalian Embryos: Is There Room for Improvement?

Cells, Journal Year: 2024, Volume and Issue: 13(12), P. 996 - 996

Published: June 7, 2024

Preimplantation embryo culture, pivotal in assisted reproductive technology (ART), has lagged innovation compared to selection advancements. This review examines the persisting gap between vivo and vitro development, emphasizing need for improved culture conditions. While humans this is hardly estimated, animal models, particularly bovines, reveal clear disparities developmental competence, cryotolerance, pregnancy live birth rates vitro-produced (IVP) vivo-derived (IVD) embryos. Molecular analyses unveil distinct differences morphology, metabolism, genomic stability, underscoring refining conditions better ART outcomes. To end, a deeper comprehension of oviduct physiology transport crucial grasping embryo–maternal interactions’ mechanisms. Research on autocrine paracrine factors, extracellular vesicles tract interactions, elucidates vital communication networks successful implantation pregnancy. In vitro, confinement, density are key factors boost development. Advanced dynamic systems mimicking fluid mechanical stimulation oviduct, through vibration, tilting, microfluidic methods, use innovative softer substrates, hold promise optimizing

Language: Английский

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Implicit bias in diagnosing mosaicism amongst preimplantation genetic testing providers: results from a multicenter study of 36 395 blastocysts

Human Reproduction, Journal Year: 2023, Volume and Issue: 39(1), P. 258 - 274

Published: Oct. 23, 2023

Abstract STUDY QUESTION Does the diagnosis of mosaicism affect ploidy rates across different providers offering preimplantation genetic testing for aneuploidies (PGT-A)? SUMMARY ANSWER Our analysis 36 395 blastocyst biopsies eight laboratories revealed that euploidy were significantly higher in reporting low mosaicism. WHAT IS KNOWN ALREADY Diagnoses consistent with chromosomal have emerged as a third category possible embryo outcomes following PGT-A. However, era mosaicism, selection has become increasingly complex. Biological, technical, analytical, and clinical complexities interpreting such results led to substantial variability PGT-A clinics. Critically, it remains unknown whether these differences impact number euploid embryos available transfer. Ultimately, this may outcomes, important implications patients. DESIGN, SIZE, DURATION In international, multicenter cohort study, we reviewed consecutive results, obtained from 10 035 patients 11 867 treatment cycles, conducted between October 2015 2021. A total 17 IVF centers, providers, five countries three continents participated study. All blastocysts tested using trophectoderm biopsy next-generation sequencing. Both autologous donation cycles assessed. Cycles structural rearrangements excluded analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS The randomly categorized (A H). Providers B, C, D, E, F, G, H all reported whereas Provider either or aneuploid. Ploidy analyzed multilevel mixed linear regression. Analyses adjusted maternal age, paternal oocyte source, biopsied, day biopsy, provider, appropriate. We compared associations including chromosomally normal (euploid) determined be suitable MAIN RESULTS AND THE ROLE OF CHANCE mean age (±SD) was 36.2 (±5.2). findings reveal strong association provider Amongst seven varied 3.1% 25.0%. After adjusting confounders, observed significant difference likelihood diagnosing (P &lt; 0.001), ranging 6.5% (95% CI: 5.2–7.4%) B 35.6% 32.6–38.7%) E. Notably, highest lowest (Provider B: euploidy, 55.7% 54.1–57.4%), 5.2–7.4%); H: 44.5% 43.6–45.4%), 9.9% 9.2–10.6%)); D: 43.8% 39.2–48.4%), 11.0% 7.5–14.5%)). Moreover, overall chance having at least one transfer when not reported, other (OR = 1.30, 95% 1.13–1.50). Differences mosaic raise further concerns regarding accuracy relevance predictions. While confirmed equivalent blastocysts, found proportion are used treatment. LIMITATIONS, REASONS FOR CAUTION Due retrospective nature can ascertained, however, causality cannot established. Certain parameters grade dataset. Furthermore, certain platform-related clinic-specific factors readily quantifiable explicitly captured our As such, full elucidation potential confounders accounting possible. WIDER IMPLICATIONS FINDINGS highlight need standardization quality assurance industry. decision ultimately reduce success cycle by limiting pool embryos. Until diagnoses accurately reflect biological variability, warrants utmost caution. prudent approach is imperative, determine failure some FUNDING/COMPETING INTEREST(S) This work supported Torres Quevedo Grant, awarded M.P. (PTQ2019-010494) Spanish State Research Agency, Ministry Science Innovation, Spain. M.P., L.B., A.R.L., A.L.R.d.C.L., N.P.P., D.S., F.A., A.P., B.M., L.D., F.V.M., M.R., E.P.d.l.B., A.R., R.V. no competing interests declare. B.L., R.M., J.A.O. time employees IB Biotech, genetics company Instituto Bernabeu group, which performs testing. M.G. employee Novagen, Cegyr, TRIAL REGISTRATION NUMBER N/A.

Language: Английский

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Mosaic results after preimplantation genetic testing for aneuploidy may be accompanied by changes in global gene expression

Frontiers in Molecular Biosciences, Journal Year: 2023, Volume and Issue: 10

Published: April 14, 2023

Aneuploidy in preimplantation embryos is a major cause of human reproductive failure. Unlike uniformly aneuploid embryos, diagnosed as diploid-aneuploid mosaics after genetic testing for aneuploidy (PGT-A) can develop into healthy infants. However, the reason why these achieve full competence needs further research. Current RNA sequencing techniques allow investigation transcriptome, providing new insights molecular mechanisms embryo development. In this prospective study, using euploid gene expression control, we compared transcriptome profiles inner cell mass and trophectoderm samples from blastocysts with different levels chromosomal mosaicism. A total 25 were analyzed 14 previous PGT-A diagnosis, including five low-level mosaic four high-level embryos. Global visualized cluster heatmaps correlated original diagnosis. addition, distance based on number differentially expressed genes increased level, to controls. Pathways involving apoptosis, mitosis, protein degradation, metabolism, mitochondrial energy production among most deregulated within Retrospective analysis duration blastomere cycles revealed several mitotic delays controls, additional evidence status. Overall, findings suggest that results are not simply misdiagnosis by-product, but may also have genuine identity compatible their potential.

Language: Английский

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Obesity may impair response to ovarian stimulation. A retrospective observational study on oocyte quality

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Sept. 30, 2024

Background Ovulatory dysfunction is more common in women with obesity. Body fat distribution also crucial because anovulatory have a greater waist circumference and abdominal than ovulatory of similar BMI. The primary aim the present study to determine whether there relationship between BMI reproductive characteristics, including hormonal values, antral follicle count (AFC), endometrial assessment at transvaginal ultrasound evaluation (TVUS) during controlled ovarian stimulation (COS), oocyte retrieval after Ovum Pick-Up (OPU). Methods Data from cohort 183 patients were analyzed divided into three groups based on weight status: normal weight, overweight, Evaluated characteristics included: age, basal values follicle-stimulating hormone (FSH), luteinizing (LH), 17-beta-estradiol (E2), thyroid stimulating (TSH), anti-müllerian (AMH), antral-follicle-count duration COS, E2, progesterone last monitoring, TVUS thickness monitoring before OPU, FOI OPU. Additionally, number meiosis II oocytes retrieved (MII), total dose FSH administered, ratio MII OSI registered. Results AMH levels significantly lower obese compared overweight (1.05 IQR 1.20, 1.58 2.16, 1.32 1.38, respectively, p -value = 0.032). When looking MII/FSH ratio, group showed median value 3.3 an 4.0, 2.3 1.9, had 2.6 2.8. Those data statistically significant ( 0.049). Conclusion These results emphasize importance considering status fertility treatment planning.

Language: Английский

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Time-lapse analysis of embryos classified as euploid, mosaic, and aneuploid after embryonic trophectoderm biopsy

Journal of Assisted Reproduction and Genetics, Journal Year: 2025, Volume and Issue: 42(1), P. 125 - 138

Published: Jan. 1, 2025

Language: Английский

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Case report: re-biopsy rescues a to-be-discarded segmental aneuploid embryo resulting in a healthy pregnancy with normal prenatal testing results

Journal of Assisted Reproduction and Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский

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Healthy Live Births after the Transfer of Mosaic Embryos: Self-Correction or PGT-A Overestimation?

Genes, Journal Year: 2023, Volume and Issue: 15(1), P. 18 - 18

Published: Dec. 21, 2023

The implementation of next generation sequencing (NGS) in preimplantation genetic testing for aneuploidy (PGT-A) has led to a higher prevalence mosaic diagnosis within the trophectoderm (TE) sample. Regardless, mosaicism could potentially increase rate live-born children with chromosomic syndromes, though available data from transfer embryos putative PGT-A are scarce but reassuring. Even lower implantation and miscarriage rates, can develop into healthy live births. Therefore, this urges an explanation disappearance aneuploid cells throughout development, provide guidance management clinical practice. Technical overestimation mosaicism, together some sort “self-correction” mechanisms during early post-implantation stages, emerged as potential explanations. Unlike animal model, which elimination genetically abnormal future fetal lineage been demonstrated, human capability remains unverified even germ layer displays aneuploidy-induced cell death preference rates apoptosis inner mass (ICM) than TE cells. Moreover, reported differential dynamics proliferation between euploid, mosaic, embryos, pro-apoptosis gene products (cfDNA mRNA) extracellular vesicles identified blastocoel fluid, may support hypothesis mechanism purge embryo Alternative hypotheses, like correction by extrusion trisomy chromosome or monosomic duplication, even, they represent extremely rare phenomenon. On other hand, technical limitations analysis lead inaccuracy diagnoses, identifying “mosaic” those that uniformly euploid aneuploid. NGS assumption “intermediate copy number profiles” evidence mixture single biopsy be poorly predictive cases diagnosis. Additionally, concordance found ICM biopsies displaying is expected, it correlates differently depending on type (whole versus segmental) level reported. Thus, low-/medium-level (<50%), would rarely involve regions. However, high-level mosaics (≥50%), should display prevalence, revealing more uniform most representing variation range, therefore might impair birth rate.

Language: Английский

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