A novel functional assay based on patient-derived endometrial organoids and blastoids predicts the success of embryo transfer

Abstract Successful embryo implantation requires complex interactions between the embryo and the endometrium. Improvements in embryo testing have led to increased success rates for embryo transfer following in vitro fertilization, however, even with euploid embryos under ideal conditions, failure occurs in more than 30% of cases. Methods for diagnosing and improving endometrial function are currently lacking. Here we developed a functional test (“Simbryo FX”) for the ability of the endometrium to support embryo implantation. We collected endometrial biopsy samples from over 100 patients, and used these to grow endometrial organoids. We interacted these organoids with blastoids, pluripotent stem cell based models of the human blastocyst, and measured the hCG produced by the blastoids as well as the degree to which the blastoids invaded the organoids. We found that both of these measures correlated with clinical outcomes, and that combining them allowed us to predict the likelihood of failure in the next embryo transfer with high specificity. Thus, interacting patient-derived endometrial organoids with blastoids represents a promising approach to evaluating endometrial function among patients preparing for embryo transfer.