O-125 Application of artificial intelligence using big data to devise and train a machine learning model on over 63,000 human embryos to automate time-lapse embryo annotation
Authors: Campbell A , Smith R , Petersen B , Moore L , Khan A , Barrie A 
Published: June 2022

Abstract

Study question
Can a machine learning (ML) model, developed using modern neural network architecture produce comparable annotation data; utilisable for algorithmic outcome prediction, to manual time-lapse annotations?

Summary answer
The model automatically annotated unseen embryos with comparable results to manual methods, generating morphokinetic data to enable comparably predictive outputs from an embryo selection algorithm.

What is known already
The application of artificial intelligence across healthcare industries, including fertility, is increasing. Several ML models are available that seek to generate or analyse embryo images and morphokinetic data, and to determine embryo viability potential. Along with photographic images, the use of time-lapse in IVF laboratories has amassed numeric data, resulting predominantly from annotated manual assessment of images over time. Embryo annotation practice is variable in quality, can be subjective and is time-consuming; commonly taking several minutes per embryo. The development of rapid, accurate automatic annotation would represent a significant time-saving as well as an increase in reproducibility and accuracy.

Study design, size, duration
Multicentre quality assured annotation data from 63,383 time-lapse monitored embryos (EmbryoScope®), comprising over 400 million individual images, were used to train a ML model to automatically generate morphokinetic annotations. Data was derived from 8 UK clinics within a cohesive group between 2012-2021. Accuracy was assessed using 900 unseen embryos (with live birth outcome) by comparing the output of an established in-house, prospectively validated embryo selection model when the input was either ML-automated, or manual annotations.

Participants/materials, setting, methods
Multi-focal plane images were processed on the Azure cloud (Microsoft) and resampled to 300x300 pixels. A Laplacian-based focal stacking algorithm merged frames into a single image. The model consisted of an EfficientNetB4 Convolutional Neural Network classifier to extract features and classify the stage of embryo images. A Temporal Convolutional Network interpreted a time-series of image features; producing annotations from pronuclear fading through to blastocyst. Soft localisation loss function used QA data to integrate annotation subjectivities.

Main results and the role of chance
The ML model rapidly and automatically generated annotations. Efficacy and comparability of the ML model to automate reliable, utilisable annotations was demonstrated by comparison with manual annotation data and the ML model’s ability to auto-generate annotations which could be used to predict live birth by providing annotation data to an established, validated in house embryo selection model. Live birth-predictive capability was measured, and benchmarked against manual annotation, using the area under the receiver operating characteristic curve (AUC).
When tested on time-lapse images, collected from pronuclear fading to full blastulation, representing 900 previously unseen, transferred blastocysts where live birth outcomes were blinded, the in-house developed auto-annotation ML model resulted in an AUC of 0.686 compared with 0.661 for manual annotations, for live birth prediction.
Auto annotation using the developed model took only milliseconds to complete per embryo. The developed auto-annotation model, built and tested on large data, is considered suitable for productionisation with the aim of being validated and integrated into an application to support IVF laboratory practice.

Limitations, reasons for caution
Whilst this model was trained to recognise key morphokinetic events, there are other morphokinetic variables that may be useful in the prediction of live birth and further improve embryo selection, or deselection, ability. Akin to manual interpretation, some embryos may fail to be annotated or need second opinion.

Wider implications of the findings
There is increasing evidence supporting the application of ML to utilise big data from time-lapse imaging and fertility care generally. Whilst promising benefits to IVF clinics and patients, responsible use of data is required alongside large high-quality datasets, and rigorous validation, to ensure safe and robust applications.

Trial registration number
N/A