P-569 Non-Invasive Preimplantation Genetic Testing for Aneuploidy (niPGT-A) Using Nanopore Sequencing on Spent Embryo Culture Medium: A Comparative Experimental Study
Notice bibliographique
Résumé
Abstract Study question Can non-invasive aneuploidy detection using nanopore sequencing of spent embryo culture medium (SEM) replace PGT-A of trophectoderm biopsy (TEB) samples? Summary answer Concordance of 80% for good-quality SEM confirm feasibility of nanopore-sequencing, while low-quality/day-5 samples show reduced concordance. The procedure can complement but not replace other methods. What is known already PGT-A increases the chances of identifying a viable embryo, but the invasive biopsy required for PGT-A is technically challenging and may negatively impact embryo viability. The analysis of SEM holds promise for non-invasive PGT-A; however various technical challenges remain, raising concerns about its clinical utility. Study design, size, duration In this experimental comparative study, the detection of aneuploidy in SEM samples using nanopore sequencing technology is compared to routine PGT-A of TEB samples. A total of 174 SEM samples of day (D) 5, D6 or D7 blastocysts from 41 patients undergoing fertility treatment were analyzed for aneuploidy and compared to PGT-A results of corresponding TEB samples. The study was approved by the Ethic Committee of the Medical University Vienna (EK-1397/2022). Participants/materials, setting, methods For the niPGT-A analysis, SEM samples were amplified using whole genome amplification (WGA) and prepared for nanopore sequencing on the portable MinION sequencing device. A nanopore-specific data analysis pipeline was optimized for automated aneuploidy calling in SEM samples, and the results were compared to routine TEB-based PGT-A using array comparative genomic hybridization (aCGH). Concordance rates were stratified based on multiple criteria to identify conditions that maximize consistency and support potential clinical application of SEM analysis. Main results and the role of chance This is the first experimental study, systematically evaluating nanopore sequencing for aneuploidy analysis using SEM. PGT-A results of both TEB and SEM were successfully generated and compared for 143 embryos (29 D5 and 114 D6/7 samples). Sample-level concordance for D5 samples was significantly lower (51.7%), compared to D6/7 samples, showing concordance rates of 77.2%. For good-quality D6/7 samples, concordance reached 80.4% (82/102 samples concordantly euploid or aneuploid). Sex chromosomes were concordantly detected in 91.6% of all included samples. Although maternal contamination cannot be completely ruled out, no statistically significant evidence was observed, as false-negative euploid, female results were not overrepresented. Among 28 false-negative samples (SEM: euploid, TEB: aneuploid), 13 (46.4%) showed only segmental (6/28, 21%) or mosaic (7/28, 25%) aneuploidies in TEB, suggesting potential uncertainty in embryo status as previously reported. Segmental aneuploidies were accurately identified in 6 SEM samples from cases with known parental translocations. Notably, one segmental aneuploidy linked to a known translocation carrier was detected only in SEM. Limitations, reasons for caution The reference method aCGH is limited in resolution compared to NGS-based approaches. Additionally, TEB-based PGT-A results in general might not always represent the whole embryo, especially for mosaic and segmental results. Whole blastocyst screening as reference would therefore be ideal, but legally not possible in this study. Wider implications of the findings Concordance rates of 80% for good-quality D6/7 SEM samples compared to invasive TEB samples confirm feasibility of this fast and cost-effective technology. However, reduced concordance in D5/low DNA samples highlights limitations in clinical applicability. Robust validation and methodological adaptations need to be implemented before niPGT-A might replace invasive PGT-A. Trial registration number No
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».