Omics approaches in embryonic microenvironment research: a narrative review

Abstract Assisted reproductive technology (ART), notably in vitro fertilization–embryo transfer (IVF-ET), has become a primary therapeutic strategy for addressing rising infertility rates worldwide. Embryo quality, culture medium conditions, and endometrial receptivity are the core determinants of IVF-ET success, while elective single blastocyst transfer (eSBT), the mainstream strategy for reducing multiple pregnancy risks, still lacks standardized and high-predictivity selection criteria due to the limitations of morphological embryo assessment. The advent of high-throughput sequencing has driven a paradigm shift in embryonic microenvironment research, from isolated single-omics analyses to integrated multi-omics approaches (proteomics, metabolomics, transcriptomics, genomics, microbiomics, etc.), which provide comprehensive molecular insights into embryo development and implantation. This narrative review systematically collates and analyzes the latest research progress of multi-omics technologies in the two core embryonic microenvironments (in vitro embryo culture system and uterine implantation milieu), summarizes the potential molecular biomarkers identified by various omics approaches and their clinical application value, and clarifies the key bottlenecks of current research (e.g., low reproducibility, non-standardized detection protocols, exogenous contamination in genomic analysis). A total of 57 relevant articles published between 1990 and 2021 were retrieved and included from the PubMed database for this review. We further prospect the application potential of emerging multi-omics technologies (single-cell multi-omics, spatial multi-omics) in this field and propose targeted solutions for existing research challenges. Collectively, multi-omics integration has emerged as a pivotal research focus in reproductive technology, and its clinical translation is expected to optimize embryo selection strategies, improve endometrial receptivity assessment accuracy, and ultimately enhance the clinical pregnancy and live birth rates of IVF-ET.