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Semiconductor Sequencing for Preimplantation Genetic Testing for Aneuploidy
Published on: August 25, 2019
Improving embryo ploidy prediction: a machine learning approach using morphokinetic meta-variables and clinical data
Enric Güell-Penas1, Minerva Ferrer-Buitrago2, Empar Ferrer I Robles2
1Consultfiv Data Science, Valls, Spain; Centre Procrear, Reus, Spain.
Research Question:
Can a machine learning model integrating time-lapse morphokinetic meta-variables with clinical data predict embryo aneuploidy accurately for improved non-invasive embryo selection?
Design:
A retrospective multicentre cohort study using time-lapse data from 1190 blastocysts from nine Spanish fertility clinics (2017-2024), with 70% (n = 833) and 30% (n = 357) used for model training/testing and external validation, respectively. The primary dataset included well-defined outcomes (live birth or aneuploidy diagnosis via preimplantation genetic testing). The LIFE Predict v1.1 model integrated clinical data and novel morphokinetic meta-variables (range and mean absolute error) representing deviations from expected embryo development. Model performance was assessed using area under the receiver operating characteristic curve (AUC-ROC) and confusion matrix metrics. Logistic regression was used to calculate OR for risk of aneuploidy. Morphological assessments using ASEBIR grading were combined with algorithmic scoring.
Results:
The final ensemble model achieved an AUC of 0.824 (95% CI 0.796-0.857) in cross-validation and 0.818 (95% CI 0.794-0.851) in external validation. The LIFE Predict v1.1 score showed a significant inverse relationship with risk of aneuploidy, with each one-point decrease increasing the odds of aneuploidy by 76% (OR = 1.76, 95% CI 1.52-2.05). The aneuploidy rate decreased across ascending score quartiles: 76.4% (lowest), 64.0%, 25.8% and 13.3% (highest). Combining morphological grading with the LIFE Predict v1.1 model revealed substantial risk stratification within identical morphological categories, with A-grade (Day 5) embryos showing aneuploidy rates from 11-14% (highest score quartiles) to 60-86% (lowest quartiles).
Conclusions:
The LIFE Predict v1.1 model predicts embryo outcomes accurately using morphokinetic meta-variables and clinical data, providing actionable risk stratification that complements conventional morphological assessment for enhanced non-invasive embryo selection. Prospective clinical validation is required to confirm its real-world utility.

