Motivation: Polygenic embryo screening (PES) is a new technology in reproductive medicine, whereby human in-vitro fertilization embryos are screened for their genetic risk of complex, polygenic diseases. PES aims to reduce the burden of polygenic diseases in offspring by prioritizing the selection of low-risk embryos. However, given that polygenic diseases are usually late-onset, PES outcomes cannot be evaluated empirically and must be estimated by epidemiological modeling. The commonly used liability threshold model has been previously used to predict PES outcomes. However, predictions rely on complex sets of equations, some of which require numerical integration or simulation. Further, previous models failed to account for the possibility that the selected embryo will not be born. Results: Here, we present PEStimate, a freely available online app for predicting PES outcomes when screening for a single disease. PEStimate predicts the offspring risk with and without PES, as well as plots of the risk reduction vs key parameters. Users can adjust the number of available embryos, the live birth rate, the disease prevalence and heritability, the accuracy of the genetic risk predictor, the embryo selection method, the genetic risk of parents, and the disease status of parents and siblings. Our new model for PES, which includes the possibility of embryo implantation failure, shows that risk reductions have been previously overestimated. PEStimate provides geneticists, healthcare professionals, patients, policymakers, and other stakeholders a necessary tool for examining the impact of PES and weighing its potential benefits against expected personal and societal harms. Availability and Implementation: PEStimate is freely available at: https://polygenicembryo.shinyapps.io/pestimate. The source code is available at: https://github.com/Lirazk/PEStimate.

SC is a paid consultant and stock owner at MyHeritage and a collaborator of Juno Genetics.

National Human Genome Research Institute of the National Institutes of Health (R01-HG011711)

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