Predicting time to live birth with deep learning embryo ranking: a novel multiple imputation approach

STUDY QUESTION: What is the clinical utility of embryo selection algorithms in estimating the time to live birth (TTLB)? SUMMARY ANSWER: Using multiple imputations, the clinical utility of embryo selection algorithms was estimated, showing their potential to improve prediction of TTLB compared to manual ranking. WHAT IS KNOWN ALREADY: Estimation of the clinical utility of embryo selection algorithms is challenging due to the unknown outcomes of non-transferred embryos. Existing studies have tried to mitigate the unknown outcome by using a biased subsample of the observed treatments or constructing treatments based on embryos from different patients. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study in a university-affiliated private IVF center. Treatments performed from 2015 through 2022 were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: Three thousand seven hundred and eighty-three treatments with a total of 17 914 usable embryos, among these, 7571 embryos were transferred in either fresh or vitrified/warmed transfers. The outcome of non-transferred embryos was estimated using the multiple imputation by chained equations (MICE) procedure. MAIN RESULTS AND THE ROLE OF CHANCE: The average TTLB for the deep learning algorithm was 1.68 (95% CI: 1.63-1.72) transfers which was 6.1% shorter than the average TTLB of 1.78 (95% CI: 1.73-1.83) transfers for manual ranking. Measuring the algorithm ranking performance on the population level resulted in an area under the receiver operating characteristic curve (AUC) of 0.633 (95% CI: 0.620-0.645) while the average performance on the treatment level was 0.672 (95% CI: 0.656-0.687). LIMITATIONS, REASONS FOR CAUTION: The proposed methods rely on an accurate prediction of the missing outcomes. As many other factors besides embryo quality will impact the actual outcome, the estimated TTLB can only approximate the actual clinical utility. In addition, the estimated TTLB in this study is only applicable to the specific dataset. WIDER IMPLICATIONS OF THE FINDINGS: This study suggests that embryo selection algorithms could potentially improve clinical outcomes in IVF treatments by increasing the likelihood of live births compared to traditional morphological gradings hence increasing the efficacy and success rates of assisted reproductive technology. STUDY FUNDING/COMPETING INTEREST(S): No funding was received to support this study. L.B. reports Contract in Fundación IVI, Instituto de Investigación Sanitaria, La Fe (Valencia, Spain). M. J. is an employee at Vitrolife A/S. J.B. is an employee and shareholder at Vitrolife A/S. E.T.P. has no financial or personal interests related to the research. M.M. reports funding from ISCIII (PI21/00283), cofounded by ERDF, 'A way to make Europe' awarded to M.M. for the submitted work; Contract in Fundación IVI, Instituto de Investigación Sanitaria, La Fe (Valencia, Spain), and Contract in IVIRMA Valencia; and honoraria from various companies, including Merck, Vitrolife, MSD Ferring, AiVF, Theramex, Gedeon Richter, Genea Biomedx, and Life Whisperer. TRIAL REGISTRATION NUMBER: N/A.