P-520 Analyses of mosaic embryos reveal critical regions on human chromosome 11 that involve embryo implantation

Abstract

Abstract Study question Why some mosaic embryos can be implanted, whereas others cannot? What are the secrets hidden in the human genome that control embryo implantation? Summary answer By data-mining genomic information from PGT-A results of 109 mosaic embryos, we have defined the critical regions in chr11 that play essential roles in implantation. What is known already Embryo implantation is usually a bottleneck step for a successful IVF treatment. What factors control the embryo implantation process has been pursued for many years, and the answers remain largely unknown. PGT-A is a widely applied procedure to identify embryos with normal diploid chromosomes to increase the clinical pregnancy rate per embryo transfer. However, some poor responder patients may only have mosaic embryos that can be used for transfer. We thus investigate the critical regions of the human chromosomes that are important for controlling embryo implantation. Study design, size, duration One hundred and nine mosaic blastocysts were analyzed based on PGT-A assay from 94 patients (ages ranging from 30 to 49 years old, mean age = 38.9 years) undergoing IVF between November 2020 and March 2022. The impact of chromosomal regions on implantation was explored by analyzing the sequencing results together with the pregnancy outcome of mosaic embryos. Additional published outcome data of 1000 mosaic embryo transfers was used to confirm our findings. Participants/materials, setting, methods Pregnant outcomes were followed, including hCG examination, sac formation, and live birth. Whole genome data analysis was performed using individual PGT-A results. Different types of chromosome abnormalities were calculated, and heatmap and clustering analysis were used to define the critical chromosome regions for embryo implantation. In addition, gene set enrichment and pathway analyses were conducted to reveal the functions of genes within the critical regions. Main results and the role of chance Among the transferred 109 mosaic embryos, the clinical outcomes of hCG positive, sac formation, and live birth rates were 45.8%, 42.2%, and 32.1%, respectively. There were 74 (67.8%) and 35 (32.1%) embryos carrying single and multiple mosaic chromosomes, respectively, resulting in 182 chromosomal mosaicism events. The trisomy mosaicism (133/182, 73.0%) occurred with higher frequency than monosomy mosaicism (49/182, 26.9%). Using the heatmap and clustering analysis, our data showed clustered monosomy mosaicism in non-pregnant embryos, especially for chr2, chr4, chr11, chr19, and chr22. Further refinement using segmental mosaic embryos has identified the critical regions, ranging from 10M to 40M in size on different chromosomes that are involved in hundreds of protein-coding genes and known dosage-sensitive genes. Importantly, functional analyses of the genes within the critical regions of chromosome 11 revealed enrichments in embryo invasion and angiogenesis, and suggest that loss of the chromosomal copy of these regions may result in implantation failure. Limitations, reasons for caution It’s still preliminary. More data is required to further confirm the conclusion. Wider implications of the findings Our study provides insights into the chromosomal regions involved in human embryo implantation and will improve the embryo prioritizing strategy in future IVF clinics. Importantly it is the first time the genomics information and gene-mapping strategy have been applied in mosaic embryos to uncover mechanisms underlying human embryo implantation. Trial registration number not applicable