A pilot study to investigate the clinically predictive values of copy number variations detected by next-generation sequencing of cell-free deoxyribonucleic acid in spent culture media
Notice bibliographique
Résumé
Objective Analysis of cell free DNA in spent culture media has been identified as a non-invasive alternative to trophectoderm biopsy for PGT-A. However, the clinical value has not been well studied. We performed a pilot study with the primary interest of estimating the positive predictive value of copy number variations to predict nonviable or aneuploid embryos and investigate the false positive risk. Design Diagnostic/prognostic accuracy study. Subjects Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF centre. Intervention Embryo selection was performed according to conventional grading, blinded to non-invasive PGT-A results. After clinical outcomes were established, spent culture media samples were analyzed. Main outcome measures Prognostic accuracy of copy number variations according to niPGT-A results to predict nonviability or clinical aneuploidy. Results One-hundred twenty patients completed the study. Interpretations of NGS profiles were as follows: 7.5% (n=9) failed quality control; 62.5% (n=75) no copy number variations detected; 30% (n=36) abnormal copy number detected. Stratification of abnormal NGS profiles were as follows: 15% (n=18) whole chromosome; 15% (n=18) uncertain reproductive potential. Intermediate copy number variation was evident in 27.8% (n=5) of the whole chromosome abnormalities. Negative predictive value for samples with no detected abnormality was 57.3% (43/75). Whole chromosome abnormality was associated with a positive predictive value of 94.4% (17/18), lower sustained implantation rate (5.6%, 1/18), and higher relative risk for nonviability compared to no detected abnormalities (RR 2.21, 95% CI:1.66-2.94) (p<0.001). No other copy number variations were associated with significant differences in sustained implantation or relative risks for nonviability. Unequal sex chromosome proportions suggested that maternal contamination was not uncommon. A secondary descriptive analysis of 705 supernumerary embryos revealed proportions of NGS profile interpretations similar to the transferred cohort. Significant differences in MAPD between certain subcategories of CNV abnormalities were apparent. Conclusion Whole chromosome abnormalities were associated with high positive predictive value and significant relative risk for nonviability. Embryos associated with other copy number variations had sustained implantation rates similar to those with no abnormalities detected. Further studies are required to validate the clinical applicability of non-invasive PGT-A. Analysis of cell free DNA in spent culture media has been identified as a non-invasive alternative to trophectoderm biopsy for PGT-A. However, the clinical value has not been well studied. We performed a pilot study with the primary interest of estimating the positive predictive value of copy number variations to predict nonviable or aneuploid embryos and investigate the false positive risk. Diagnostic/prognostic accuracy study. Patients aged 35 and younger with an indication for IVF-ICSI and elective single frozen embryo transfer at a single, private IVF centre. Embryo selection was performed according to conventional grading, blinded to non-invasive PGT-A results. After clinical outcomes were established, spent culture media samples were analyzed. Prognostic accuracy of copy number variations according to niPGT-A results to predict nonviability or clinical aneuploidy. One-hundred twenty patients completed the study. Interpretations of NGS profiles were as follows: 7.5% (n=9) failed quality control; 62.5% (n=75) no copy number variations detected; 30% (n=36) abnormal copy number detected. Stratification of abnormal NGS profiles were as follows: 15% (n=18) whole chromosome; 15% (n=18) uncertain reproductive potential. Intermediate copy number variation was evident in 27.8% (n=5) of the whole chromosome abnormalities. Negative predictive value for samples with no detected abnormality was 57.3% (43/75). Whole chromosome abnormality was associated with a positive predictive value of 94.4% (17/18), lower sustained implantation rate (5.6%, 1/18), and higher relative risk for nonviability compared to no detected abnormalities (RR 2.21, 95% CI:1.66-2.94) (p<0.001). No other copy number variations were associated with significant differences in sustained implantation or relative risks for nonviability. Unequal sex chromosome proportions suggested that maternal contamination was not uncommon. A secondary descriptive analysis of 705 supernumerary embryos revealed proportions of NGS profile interpretations similar to the transferred cohort. Significant differences in MAPD between certain subcategories of CNV abnormalities were apparent. Whole chromosome abnormalities were associated with high positive predictive value and significant relative risk for nonviability. Embryos associated with other copy number variations had sustained implantation rates similar to those with no abnormalities detected. Further studies are required to validate the clinical applicability of non-invasive PGT-A.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 source (Gemma direct ou Codex distillé), 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 ».