Recurrent pregnancy loss (RPL) affects up to 5% of couples and remains a significant clinical and emotional burden. While chromosomal abnormalities account for about half of early pregnancy losses, the genetic basis of many euploid miscarriages remains poorly understood. Ongoing efforts at UCSF are using whole genome sequencing (WGS) to identify candidate lethal variants associated with miscarriage, but validating their impact on human development is challenging. This project aims to establish human stem cell-derived embryo-like structures, or “embryoids,” as a model system to study the functional consequences of lethal variants. Embryoids mimic key stages of early human development, including blastocyst formation and gastrulation, providing an ethical and human-specific platform for investigating how candidate variants impair developmental milestones. By introducing RPL-associated variants into stem cells and evaluating their ability to form embryoids, this study seeks to uncover critical insights into the genetic mechanisms underlying RPL.