O-196 Evidence-based management of mosaic embryos - a single Centre experience from prospective transfer and birth outcomes of 565 mosaic embryos
Bibliographic record
Abstract
Abstract Study question What are the pregnancy and neonatal outcomes of prospective transfer of 565 mosaic embryos and what are the key determinants influencing the outcome? Summary answer Mosaic (diploid/aneuploid) embryos have a significant developmental potential with good neonatal outcomes allowing personalized management and evidence based prioritization of embryos for transfer. What is known already Since the first report of healthy babies born after mosaic transfer, the gradual accumulation of knowledge on mosaic embryo transfers in the International Registry of Mosaic Embryo Transfers provided the necessary reassurance for clinical management of mosaic embryos. Large and comprehensive data from single centres with consistent clinical genetic counselling and laboratory practices for preimplantation and prenatal testing offer valuable contribution to the current practices. The aim of this study was to evaluate the pregnancy and neonatal outcomes after mosaic embryo transfers and to evaluate for associations between embryo genetic aberrations, static morphology and specific outcomes. Study design, size, duration This is a retrospective cohort study that took place in a single academic IVF centre (The CReATe Fertility Centre, Toronto, Canada), where we analysed the results from high resolution PGT-A, embryo morphologic features and pregnancy outcomes of 3529 frozen embryo transfers from 2016-2022. Associated patient demographic data, transfer outcome and neonatal outcome of 2964 euploid and 565 mosaic embryo transfers were analyzed. Participants/materials, setting, methods All patients received genetic counselling prior to frozen embryo transfer. High resolution NGS PGT-A was performed using the Illumina platform and BluGnome and NxClinical for data analysis. Clinically relevant findings were aberrations >10Mb and mosaicism from 25%-75%. Comparison of clinical and morphological characteristics of euploid, low-level mosaic (25%-<50% aneuploid cells in trophectoderm biopsy), and high-level mosaics (50% -75%) was performed with R-statistical package, Mathlab and SSPS software. p < 0.05 with CI 95% was considered significant. Main results and the role of chance Of the total 565 mosaic embryos transferred 77.1% had mosaicism levels ≥25%-<50% (Group1-n=436): 54.8% had segmental chromosome mosaic (SCM)gain/loss, 45.2% had whole chromosome mosaicism(WCM)(trisomy/monosomy); and 22.9% had mosaic levels of ≥ 50-<70% (Group2-n=129)(50.4% with SCM and 49.6% with WCM). The overall ongoing pregnancy rate(OPR) for mosaic embryos was 33% and the miscarriage rate was 6%. Compared with euploid embryos, mosaic embryos have significantly lower implantation (p = 0,OD0.62-CI[0.5-0.7]) and OPR(p = 0,OD0.5-CI[0.4-0.6]). Pregnancy outcomes are determined by level of mosaicism: Group1 have better implantation(p = 0.005,OD1.8-CI[1.18-2.78]) and OPR compared to Group2. High level of mosaicism independently affected the OPR of SCM(p = 0.003) and WCM(p = 0.02) embryos. WCM had lower implantation rates compared to SCM (p = 0.005,OD1.6-CI[1.15-2.27]). Mosaic monosomies had the lowest impanation and OPR of all mosaic embryos (14% and 8%,respectively). Within Group1 and Group2 good static morphology was associated with higher OPR for SCM and WCM embryos. Birth outcomes were available for 118 babies from mosaic-FET and from 802 euploid-FET. There is no difference in duration of pregnancy and birth weight between mosaic and euploid-FET. No gross-fetal anomalies were reported in the mosaic group at birth. There was one termination<20GW due to fetal anomalies and one stillbirth. For euploid transfers, 11 had fetal anomalies, there were 7-terminations and 2-stillbirths. Limitations, reasons for caution Although this is the largest single centre study to date that evaluated genomic, morphology and outcome data of mosaic transfers, the numbers are still low to analyze the impact of specific chromosomal aberrations on pregnancy outcome. Wider implications of the findings Mosaic embryos should be considered for transfer and prioritized based on the level of mosaicism, type of chromosomal aberration and static morphology. The implantation potential is lower than euploid embryos however established pregnancies result in healthy babies born at term and normal birth weight. Trial registration number CReATe Fertility Centre, Toronto, Canada
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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".