STUDY QUESTION Can an artificial intelligence (AI)-based model predict human embryo viability using images captured by optical light microscopy? SUMMARY ANSWER We have combined computer vision image processing methods and deep learning techniques to create the non-invasive Life Whisperer AI model for robust prediction of embryo viability, as measured by clinical pregnancy outcome, using single static images of Day 5 blastocysts obtained from standard optical light microscope systems. WHAT IS KNOWN ALREADY Embryo selection following IVF is a critical factor in determining the success of ensuing pregnancy. Traditional morphokinetic grading by trained embryologists can be subjective and variable, and other complementary techniques, such as time-lapse imaging, require costly equipment and have not reliably demonstrated predictive ability for the endpoint of clinical pregnancy. AI methods are being investigated as a promising means for improving embryo selection and predicting implantation and pregnancy outcomes. STUDY DESIGN, SIZE, DURATION These studies involved analysis of retrospectively collected data including standard optical light microscope images and clinical outcomes of 8886 embryos from 11 different IVF clinics, across three different countries, between 2011 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS The AI-based model was trained using static two-dimensional optical light microscope images with known clinical pregnancy outcome as measured by fetal heartbeat to provide a confidence score for prediction of pregnancy. Predictive accuracy was determined by evaluating sensitivity, specificity and overall weighted accuracy, and was visualized using histograms of the distributions of predictions. Comparison to embryologists’ predictive accuracy was performed using a binary classification approach and a 5-band ranking comparison. MAIN RESULTS AND THE ROLE OF CHANCE The Life Whisperer AI model showed a sensitivity of 70.1% for viable embryos while maintaining a specificity of 60.5% for non-viable embryos across three independent blind test sets from different clinics. The weighted overall accuracy in each blind test set was >63%, with a combined accuracy of 64.3% across both viable and non-viable embryos, demonstrating model robustness and generalizability beyond the result expected from chance. Distributions of predictions showed clear separation of correctly and incorrectly classified embryos. Binary comparison of viable/non-viable embryo classification demonstrated an improvement of 24.7% over embryologists’ accuracy (P = 0.047, n = 2, Student’s t test), and 5-band ranking comparison demonstrated an improvement of 42.0% over embryologists (P = 0.028, n = 2, Student’s t test). LIMITATIONS, REASONS FOR CAUTION The AI model developed here is limited to analysis of Day 5 embryos; therefore, further evaluation or modification of the model is needed to incorporate information from different time points. The endpoint described is clinical pregnancy as measured by fetal heartbeat, and this does not indicate the probability of live birth. The current investigation was performed with retrospectively collected data, and hence it will be of importance to collect data prospectively to assess real-world use of the AI model. WIDER IMPLICATIONS OF THE FINDINGS These studies demonstrated an improved predictive ability for evaluation of embryo viability when compared with embryologists’ traditional morphokinetic grading methods. The superior accuracy of the Life Whisperer AI model could lead to improved pregnancy success rates in IVF when used in a clinical setting. It could also potentially assist in standardization of embryo selection methods across multiple clinical environments, while eliminating the need for complex time-lapse imaging equipment. Finally, the cloud-based software application used to apply the Life Whisperer AI model in clinical practice makes it broadly applicable and globally scalable to IVF clinics worldwide. STUDY FUNDING/COMPETING INTEREST(S) Life Whisperer Diagnostics, Pty Ltd is a wholly owned subsidiary of the parent company, Presagen Pty Ltd. Funding for the study was provided by Presagen with grant funding received from the South Australian Government: Research, Commercialisation and Startup Fund (RCSF). ‘In kind’ support and embryology expertise to guide algorithm development were provided by Ovation Fertility. J.M.M.H., D.P. and M.P. are co-owners of Life Whisperer and Presagen. Presagen has filed a provisional patent for the technology described in this manuscript (52985P pending). A.P.M. owns stock in Life Whisperer, and S.M.D., A.J., T.N. and A.P.M. are employees of Life Whisperer.

The detection and removal of poor-quality data in a training set is crucial to achieve high-performing AI models. In healthcare, data can be inherently poor-quality due to uncertainty or subjectivity, but as is often the case, the requirement for data privacy restricts AI practitioners from accessing raw training data, meaning manual visual verification of private patient data is not possible. Here we describe a novel method for automated identification of poor-quality data, called Untrainable Data Cleansing. This method is shown to have numerous benefits including protection of private patient data; improvement in AI generalizability; reduction in time, cost, and data needed for training; all while offering a truer reporting of AI performance itself. Additionally, results show that Untrainable Data Cleansing could be useful as a triage tool to identify difficult clinical cases that may warrant in-depth evaluation or additional testing to support a diagnosis.

III

STUDY QUESTION Can an artificial intelligence (AI) model predict human embryo ploidy status using static images captured by optical light microscopy? SUMMARY ANSWER Results demonstrated predictive accuracy for embryo euploidy and showed a significant correlation between AI score and euploidy rate, based on assessment of images of blastocysts at Day 5 after IVF. WHAT IS KNOWN ALREADY Euploid embryos displaying the normal human chromosomal complement of 46 chromosomes are preferentially selected for transfer over aneuploid embryos (abnormal complement), as they are associated with improved clinical outcomes. Currently, evaluation of embryo genetic status is most commonly performed by preimplantation genetic testing for aneuploidy (PGT-A), which involves embryo biopsy and genetic testing. The potential for embryo damage during biopsy, and the non-uniform nature of aneuploid cells in mosaic embryos, has prompted investigation of additional, non-invasive, whole embryo methods for evaluation of embryo genetic status. STUDY DESIGN, SIZE, DURATION A total of 15 192 blastocyst-stage embryo images with associated clinical outcomes were provided by 10 different IVF clinics in the USA, India, Spain and Malaysia. The majority of data were retrospective, with two additional prospectively collected blind datasets provided by IVF clinics using the genetics AI model in clinical practice. Of these images, a total of 5050 images of embryos on Day 5 of in vitro culture were used for the development of the AI model. These Day 5 images were provided for 2438 consecutively treated women who had undergone IVF procedures in the USA between 2011 and 2020. The remaining images were used for evaluation of performance in different settings, or otherwise excluded for not matching the inclusion criteria. PARTICIPANTS/MATERIALS, SETTING, METHODS The genetics AI model was trained using static 2-dimensional optical light microscope images of Day 5 blastocysts with linked genetic metadata obtained from PGT-A. The endpoint was ploidy status (euploid or aneuploid) based on PGT-A results. Predictive accuracy was determined by evaluating sensitivity (correct prediction of euploid), specificity (correct prediction of aneuploid) and overall accuracy. The Matthew correlation coefficient and receiver-operating characteristic curves and precision-recall curves (including AUC values), were also determined. Performance was also evaluated using correlation analyses and simulated cohort studies to evaluate ranking ability for euploid enrichment. MAIN RESULTS AND THE ROLE OF CHANCE Overall accuracy for the prediction of euploidy on a blind test dataset was 65.3%, with a sensitivity of 74.6%. When the blind test dataset was cleansed of poor quality and mislabeled images, overall accuracy increased to 77.4%. This performance may be relevant to clinical situations where confounding factors, such as variability in PGT-A testing, have been accounted for. There was a significant positive correlation between AI score and the proportion of euploid embryos, with very high scoring embryos (9.0–10.0) twice as likely to be euploid than the lowest-scoring embryos (0.0–2.4). When using the genetics AI model to rank embryos in a cohort, the probability of the top-ranked embryo being euploid was 82.4%, which was 26.4% more effective than using random ranking, and ∼13–19% more effective than using the Gardner score. The probability increased to 97.0% when considering the likelihood of one of the top two ranked embryos being euploid, and the probability of both top two ranked embryos being euploid was 66.4%. Additional analyses showed that the AI model generalized well to different patient demographics and could also be used for the evaluation of Day 6 embryos and for images taken using multiple time-lapse systems. Results suggested that the AI model could potentially be used to differentiate mosaic embryos based on the level of mosaicism. LIMITATIONS, REASONS FOR CAUTION While the current investigation was performed using both retrospectively and prospectively collected data, it will be important to continue to evaluate real-world use of the genetics AI model. The endpoint described was euploidy based on the clinical outcome of PGT-A results only, so predictive accuracy for genetic status in utero or at birth was not evaluated. Rebiopsy studies of embryos using a range of PGT-A methods indicated a degree of variability in PGT-A results, which must be considered when interpreting the performance of the AI model. WIDER IMPLICATIONS OF THE FINDINGS These findings collectively support the use of this genetics AI model for the evaluation of embryo ploidy status in a clinical setting. Results can be used to aid in prioritizing and enriching for embryos that are likely to be euploid for multiple clinical purposes, including selection for transfer in the absence of alternative genetic testing methods, selection for cryopreservation for future use or selection for further confirmatory PGT-A testing, as required. STUDY FUNDING/COMPETING INTEREST(S) Life Whisperer Diagnostics is a wholly owned subsidiary of the parent company, Presagen Holdings Pty Ltd. Funding for the study was provided by Presagen with grant funding received from the South Australian Government: Research, Commercialisation, and Startup Fund (RCSF). ‘In kind’ support and embryology expertise to guide algorithm development were provided by Ovation Fertility. ‘In kind’ support in terms of computational resources provided through the Amazon Web Services (AWS) Activate Program. J.M.M.H., D.P. and M.P. are co-owners of Life Whisperer and Presagen. S.M.D., M.A.D. and T.V.N. are employees or former employees of Life Whisperer. S.M.D, J.M.M.H, M.A.D, T.V.N., D.P. and M.P. are listed as inventors of patents relating to this work, and also have stock options in the parent company Presagen. M.V. sits on the advisory board for the global distributor of the technology described in this study and also received support for attending meetings. TRIAL REGISTRATION NUMBER N/A.

IntroductionThe benefits of regular physical activity for children are significant. Previous research has addressed the quantity and quality of children's physical activity while in early childhood education and care (ECEC) settings, yet little research has investigated the social and physical environmental influences on physical activity in these settings. The outcomes of this study will be to measure these social and physical environmental influences on children's physical activity using a combination of a real-time location system (RTLS) (a closed system that tracks the location of movement of participants via readers and tags), accelerometry and direct observation.Methods and analysisThis study is the first of its kind to combine RTLSs and accelerometer data in ECEC settings. It is a cross-sectional study involving ∼100 educators and 500 children from 11 ECEC settings in the Illawarra region of New South Wales, Australia. A RTLS and Actigraph GT3X+ accelerometers will be concurrently used to measure the level and location of the children's and educators' physical activity while in outside environments. Children and educators will wear accelerometers on their hip that record triaxial acceleration data at 100 Hz. Children and educators will also wear a tag watch on their wrist that transmits a signal to anchors of the RTLS and the triangulation of signals will identify their specific location. In addition to these, up to three random periods (10–25 min in length) will be used to collect observational data each day and assessed with the classroom assessment and scoring system to measure the quality of interactions. In conjunction with the real-time location system (RTLS) and accelerometers, these observations will measure the relationship between the quality of interactions and children's physical activity.Ethics and disseminationThe results of this study will be disseminated through peer-reviewed publications and presentations. Ethical approval was obtained through the University of Wollongong Human Research Ethics Committee (HE14/330).

No abstract

Training on multiple diverse data sources is critical to ensure unbiased and generalizable AI. In healthcare, data privacy laws prohibit data from being moved outside the country of origin, preventing global medical datasets being centralized for AI training. Data-centric, cross-silo federated learning represents a pathway forward for training on distributed medical datasets. Existing approaches typically require updates to a training model to be transferred to a central server, potentially breaching data privacy laws unless the updates are sufficiently disguised or abstracted to prevent reconstruction of the dataset. Here we present a completely decentralized federated learning approach, using knowledge distillation, ensuring data privacy and protection. Each node operates independently without needing to access external data. AI accuracy using this approach is found to be comparable to centralized training, and when nodes comprise poor-quality data, which is common in healthcare, AI accuracy can exceed the performance of traditional centralized training.

No abstract