Comparing performance between clinics of an embryo evaluation algorithm based on time-lapse images and machine learning.

PURPOSE: This article aims to assess how differences in maternal age distributions between IVF clinics affect the performance of an artificial intelligence model for embryo viability prediction and proposes a method to account for such differences. METHODS: Using retrospectively collected data from 4805 fresh and frozen single blastocyst transfers of embryos incubated for 5 to 6 days, the discriminative performance was assessed based on fetal heartbeat outcomes. The data was collected from 4 clinics, and the discrimination was measured in terms of the area under ROC curves (AUC) for each clinic. To account for the different age distributions between clinics, a method for age-standardizing the AUCs was developed in which the clinic-specific AUCs were standardized using weights for each embryo according to the relative frequency of the maternal age in the relevant clinic compared to the age distribution in a common reference population. RESULTS: There was substantial variation in the clinic-specific AUCs with estimates ranging from 0.58 to 0.69 before standardization. The age-standardization of the AUCs reduced the between-clinic variance by 16%. Most notably, three of the clinics had quite similar AUCs after standardization, while the last clinic had a markedly lower AUC both with and without standardization. CONCLUSION: The method of using age-standardization of the AUCs that is proposed in this article mitigates some of the variability between clinics. This enables a comparison of clinic-specific AUCs where the difference in age distributions is accounted for.

Predicting Embryo Viability Based on Self-Supervised Alignment of Time-Lapse Videos.

With self-supervised learning, both labeled and unlabeled data can be used for representation learning and model pretraining. This is particularly relevant when automating the selection of a patient's fertilized eggs (embryos) during a fertility treatment, in which only the embryos that were transferred to the female uterus may have labels of pregnancy. In this paper, we apply a self-supervised video alignment method known as temporal cycle-consistency (TCC) on 38176 time-lapse videos of developing embryos, of which 14550 were labeled. We show how TCC can be used to extract temporal similarities between embryo videos and use these for predicting pregnancy likelihood. Our temporal similarity method outperforms the time alignment measurement (TAM) with an area under the receiver operating characteristic (AUC) of 0.64 vs. 0.56. Compared to existing embryo evaluation models, it places in between a pure temporal and a spatio-temporal model that both require manual annotations. Furthermore, we use TCC for transfer learning in a semi-supervised fashion and show significant performance improvements compared to standard supervised learning, when only a small subset of the dataset is labeled. Specifically, two variants of transfer learning both achieve an AUC of 0.66 compared to 0.63 for supervised learning when 16% of the dataset is labeled.

Automatic grading of human blastocysts from time-lapse imaging.

BACKGROUND: Blastocyst morphology is a predictive marker for implantation success of in vitro fertilized human embryos. Morphology grading is therefore commonly used to select the embryo with the highest implantation potential. One of the challenges, however, is that morphology grading can be highly subjective when performed manually by embryologists. Grading systems generally discretize a continuous scale of low to high score, resulting in floating and unclear boundaries between grading categories. Manual annotations therefore suffer from large inter-and intra-observer variances. METHOD: In this paper, we propose a method based on deep learning to automatically grade the morphological appearance of human blastocysts from time-lapse imaging. A convolutional neural network is trained to jointly predict inner cell mass (ICM) and trophectoderm (TE) grades from a single image frame, and a recurrent neural network is applied on top to incorporate temporal information of the expanding blastocysts from multiple frames. RESULTS: Results showed that the method achieved above human-level accuracies when evaluated on majority votes from an independent test set labeled by multiple embryologists. Furthermore, when evaluating implantation rates for embryos grouped by morphology grades, human embryologists and our method had a similar correlation between predicted embryo quality and pregnancy outcome. CONCLUSIONS: The proposed method has shown improved performance of predicting ICM and TE grades on human blastocysts when utilizing temporal information available with time-lapse imaging. The algorithm is considered at least on par with human embryologists on quality estimation, as it performed better than the average human embryologist at ICM and TE prediction and provided a slightly better correlation between predicted embryo quality and implantability than human embryologists.