Molecular profiling of human blastocysts reveals primitive endoderm defects among embryos of decreased implantation potential.

Human embryo implantation is remarkably inefficient, and implantation failure remains among the greatest obstacles in treating infertility. Gene expression data from human embryos have accumulated rapidly in recent years; however, identification of the subset of genes that determine successful implantation remains a challenge. It has been known for decades that morphological grading--differences in the appearance of the embryo under the microscope--correlate with implantation potential. However, this correlation is imperfect, and what these differences represent at the molecular level remain unknown. In this study, we leverage clinical morphological grading and transcriptome analyses of matched embryonic and abembryonic samples to identify factors and pathways enriched and depleted in human blastocysts of good and poor morphology. Unexpectedly, we discovered that the greatest difference was in the state of extraembryonic primitive endoderm (PrE) development, with relative deficiencies in poor morphology blastocysts. Our results suggest that implantation success is most strongly influenced by the embryonic compartment and that deficient PrE development is common among embryos with decreased implantation potential. Our study provides a valuable resource for those investigating the markers and mechanisms of human embryo implantation.