P–135 Artificial neural networks (ANNs) for live birth prediction in frozen embryo transfers: the strength of post-warmed blastocyst dynamics
Authors: Alegre L , Bori L , Coello A , Ferreira A S , Rocha J C , Cobo A , Meseguer M 
Published: August 2021

Abstract

Study question
Does the post-warmed blastocyst dynamics have an impact over the likelihood of achieving a live birth?

Summary answer
Variables related to dynamics of vitrified/warmed blastocysts have shown a greater effect on the live birth prediction than only embryo morphological quality through artificial intelligence.

What is known already
Morphological dynamics of vitrified/warmed blastocysts were described by Coello et al., in 2017. The investigated markers were the thickness of zona pellucida (µm) and blastocysts area (µm2) after warming and before transfer, the area of the inner cell mass (µm2), time of initiation of reexpansion (in minutes), and presence of collapse or contraction. They found a correlation between blastocyst reexpansion and implantation rate and developed a hierarchical model for implantation prediction. In our study, we evaluated the post-warmed blastocyst dynamics for live birth prediction by using novel artificial intelligence techniques.

Study design, size, duration
This retrospective analysis included 415 vitrified/warmed blastocysts with known live birth data. Blastocysts after warming were placed in EmbryoScope (Vitrolife) immediately until embryo transfer. Embryo evaluation and selection were performed by senior embryologists according to fresh blastocyst morphology (before vitrification). Then, parameters related to post-warmed blastocyst dynamics were calculated. Finally, these variables and the embryo morphological grade before the vitrification were used as input data for ANNs optimized with genetic algorithm for live birth prediction.

Participants/materials, setting, methods
Blastocysts were vitrified and warmed by the Cryotop method (Kitazato,Biopharma). During the period between the warming procedure and the embryo transfer, the following variables were measured with the drawing tools provided by the EmbryoViewer workstation: zona pellucida thinning (µm), blastocyst expansion (um) and the speed of these two events (µm/h). Finally, multilayer perceptron neural networks were trained with data of 331 embryos by using the backpropagation learning algorithm and tested with data of 84 embryos.

Main results and the role of chance
We trained and tested three architectures of ANNs with different input variables as follows: post-warmed variables (thinning of the zona pellucida, blastocyst expansion, thinning speed and expansion speed) and morphological grade (A, B or C) for ANN1, only post-warmed variables for ANN2 and only morphological grade for ANN3. The highest success rate when ANNs classified embryos as positive and negative live birth (LB+ and LB-) was achieved by combining post-warmed variables and morphological grade before embryo vitrification. The general accuracies for the blind tests were: 73.8% for ANN1, 66.7% for ANN2 and 71.4% for ANN3. Likewise, this combination achieved the highest AUC on test dataset to predict LB- (0.76 for ANN1, 0.74 for ANN2 and 0.67 for ANN3). However, the ANN2 trained with only post-warmed variables showed the best capacity to predict LB+ with an AUC of 0.73 (versus 0.46 for ANN1 and 0.5 for ANN3).

Limitations, reasons for caution
The main limitation is the subjectivity of manual annotations, although only one embryologist participated in this task.
Wider implications of the findings: The dynamics of vitrified/warmed blastocysts prior to embryo transfer could be more relevant variables than the morphological quality on day 5 before the cryopreservation. The analysis of embryo behavior after warming could improve clinical outcomes in frozen embryo transfers.

Trial registration number
none