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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. [ABSTRACT FROM AUTHOR]

This work describes the development and validation of a fully automated deep learning model, iDAScore v2.0, for the evaluation of human embryos incubated for 2, 3, and 5 or more days. We trained and evaluated the model on an extensive and diverse dataset including 181,428 embryos from 22 IVF clinics across the world. To discriminate the transferred embryos with known outcome, we show areas under the receiver operating curve ranging from 0.621 to 0.707 depending on the day of transfer. Predictive performance increased over time and showed a strong correlation with morphokinetic parameters. The model's performance is equivalent to the KIDScore D3 model on day 3 embryos while it significantly surpasses the performance of KIDScore D5 v3 on day 5+ embryos. This model provides an analysis of time-lapse sequences without the need for user input, and provides a reliable method for ranking embryos for their likelihood of implantation, at both cleavage and blastocyst stages. This greatly improves embryo grading consistency and saves time compared to traditional embryo evaluation methods. [ABSTRACT FROM AUTHOR]

Assessing and selecting the most viable embryos for transfer is an essential part of in vitro fertilization (IVF). In recent years, several approaches have been made to improve and automate the procedure using artificial intelligence (AI) and deep learning. Based on images of embryos with known implantation data (KID), AI models have been trained to automatically score embryos related to their chance of achieving a successful implantation. However, as of now, only limited research has been conducted to evaluate how embryo selection models generalize to new clinics and how they perform in subgroup analyses across various conditions. In this paper, we investigate how a deep learning-based embryo selection model using only time-lapse image sequences performs across different patient ages and clinical conditions, and how it correlates with traditional morphokinetic parameters. The model was trained and evaluated based on a large dataset from 18 IVF centers consisting of 115,832 embryos, of which 14,644 embryos were transferred KID embryos. In an independent test set, the AI model sorted KID embryos with an area under the curve (AUC) of a receiver operating characteristic curve of 0.67 and all embryos with an AUC of 0.95. A clinic hold-out test showed that the model generalized to new clinics with an AUC range of 0.60–0.75 for KID embryos. Across different subgroups of age, insemination method, incubation time, and transfer protocol, the AUC ranged between 0.63 and 0.69. Furthermore, model predictions correlated positively with blastocyst grading and negatively with direct cleavages. The fully automated iDAScore v1.0 model was shown to perform at least as good as a state-of-the-art manual embryo selection model. Moreover, full automatization of embryo scoring implies fewer manual evaluations and eliminates biases due to inter- and intraobserver variation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Embryo selection within in vitro fertilization (IVF) is the process of evaluating qualities of fertilized oocytes (embryos) and selecting the best embryo(s) available within a patient cohort for subsequent transfer or cryopreservation. In recent years, artificial intelligence (AI) has been used extensively to improve and automate the embryo ranking and selection procedure by extracting relevant information from embryo microscopy images. The AI models are evaluated based on their ability to identify the embryo(s) with the highest chance(s) of achieving a successful pregnancy. Whether such evaluations should be based on ranking performance or pregnancy prediction, however, seems to divide studies. As such, a variety of performance metrics are reported, and comparisons between studies are often made on different outcomes and data foundations. Moreover, superiority of AI methods over manual human evaluation is often claimed based on retrospective data, without any mentions of potential bias. In this paper, we provide a technical view on some of the major topics that divide how current AI models are trained, evaluated and compared. We explain and discuss the most common evaluation metrics and relate them to the two separate evaluation objectives, ranking and prediction. We also discuss when and how to compare AI models across studies and explain in detail how a selection bias is inevitable when comparing AI models against current embryo selection practice in retrospective cohort studies. [ABSTRACT FROM AUTHOR]

Does embryo categorization by existing artificial intelligence (AI), morphokinetic or morphological embryo selection models correlate with blastocyst euploidy? A total of 834 patients (mean maternal age 40.5 ± 3.4 years) who underwent preimplantation genetic testing for aneuploidies (PGT-A) on a total of 3573 tested blastocysts were included in this retrospective study. The cycles were stratified into five maternal age groups according to the Society for Assisted Reproductive Technology age groups (<35, 35–37, 38–40, 41–42 and >42 years). The main outcome of this study was the correlation of euploidy rates in stratified maternal age groups and an automated AI model (iDAScore® v1.0), a morphokinetic embryo selection model (KIDScore Day 5 ver 3, KS-D5) and a traditional morphological grading model (Gardner criteria), respectively. Euploidy rates were significantly correlated with iDAScore (P = 0.0035 to <0.001) in all age groups, and expect for the youngest age group, with KS-D5 and Gardner criteria (all P < 0.0001). Additionally, multivariate logistic regression analysis showed that for all models, higher scores were significantly correlated with euploidy (all P < 0.0001). These results show that existing blastocyst scoring models correlate with ploidy status. However, as these models were developed to indicate implantation potential, they cannot accurately diagnose if an embryo is euploid or aneuploid. Instead, they may be used to support the decision of how many and which blastocysts to biopsy, thus potentially reducing patient costs. [ABSTRACT FROM AUTHOR]