P-569 Non-Invasive Preimplantation Genetic Testing for Aneuploidy (niPGT-A) Using Nanopore Sequencing on Spent Embryo Culture Medium: A Comparative Experimental Study
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".