Human embryo implantation in vitro: a standardized framework for basic research and clinical translation

Abstract

Despite decades of advances in assisted reproductive technology implantation failure remains a major barrier to achieving pregnancy, contributing to infertility and early pregnancy loss. Our understanding of this stage, referred to as a "black box", is limited both by the inability to observe this process in utero and the poor translatability of animal models. For decades, our knowledge has relied solely on the Carnegie Collection, a limited set of histological specimens that precludes molecular or chronological analysis. The emergence of extended in vitro embryo culture systems offers a powerful opportunity to study the dynamic molecular and cellular events of human embryo implantation in real time. This review summarizes the current knowledge gained from the Carnegie specimens and the most recent embryo culture platforms. We highlight the limitations of existing in vitro cultures, particularly the absence of a suitable maternal endometrial environment, and underscore the need for more physiologically relevant systems. To unify research efforts and enhance clinical translatability, we propose a standardized framework for defining stages and assessing human embryo viability on the basis of morphological, temporal, and functional criteria. Establishing these benchmarks will allow for meaningful comparison across studies and accelerate the development of advanced models for investigating causes of implantation failure and pathologies manifesting later in pregnancy, such as preeclampsia. Adoption of a standardized framework is an essential step that will accelerate the development of patient-specific diagnostics and novel therapeutics to improve fertility care.

Keywords: Human embryo; endometrium; implantation; in vitro embryo cultures.