Human Fertility

Embryo–Endometrium Crosstalk: Strategies to enhance ART success

Successful embryo implantation depends on a highly coordinated and dynamic dialogue between the embryo and the endometrium. Despite significant advances in assisted reproductive technologies (ART) that have improved gamete handling, embryo culture, and cryopreservation, implantation remains a major limiting step in achieving pregnancy. Increasing evidence demonstrates that implantation success is not determined by embryo quality alone but by the intricate molecular, cellular, and immunological interactions occurring at the maternal–embryonic interface. These interactions are tightly regulated within the window of implantation, a limited period during which the endometrium becomes receptive to embryo attachment and invasion. Hormonal signalling, immune modulation, cellular adhesion molecules, and paracrine communication all contribute to this process. Disruption of embryo–endometrium crosstalk can result in implantation failure, highlighting the need to better understand and optimize this critical biological interaction.

Implantation failure remains one of the most challenging obstacles in ART, particularly for patients experiencing recurrent implantation failure despite the transfer of morphologically high-quality or euploid embryos. This underscores the clinical importance of endometrial receptivity and embryo–endometrium synchrony. Factors such as chronic endometrial inflammation, uterine structural abnormalities, immune dysregulation, altered microbiome, and suboptimal hormonal environments can compromise implantation. At the same time, laboratory practices influence embryonic signalling and developmental competence, further affecting implantation outcomes. A deeper understanding of embryo–endometrium communication provides an opportunity to move beyond a “one-size-fits-all” approach toward personalized reproductive care. Integrating molecular diagnostics, advanced imaging, and functional assays into clinical practice may improve embryo transfer timing, optimize endometrial preparation, and guide targeted therapeutic interventions. Advancing this field is essential to improve ART success rates, reduce patient burden, and shorten time to pregnancy.

This Article Collection will explore the biological and clinical dimensions of embryo–endometrium crosstalk, aligning with the journal’s focus on reproductive biology and clinical translation. Key topics include molecular and cellular mechanisms governing implantation, embryo-derived signals influencing endometrial receptivity, and immune–endocrine regulation at the maternal interface. Submissions addressing embryo selection strategies, laboratory optimization, non-invasive assessment tools, time-lapse imaging, and AI-assisted embryo evaluation are encouraged. The Collection also welcomes studies on uterine diagnostics and therapeutic approaches, including endometrial receptivity testing, microbiome profiling, advanced imaging, and management of uterine pathologies. Comparative analyses of endometrial preparation protocols, progesterone timing, luteal phase support, and vascularization will be particularly relevant. Emerging regenerative and immunomodulatory strategies may also be included. Preferred article types include original research articles, systematic reviews, narrative reviews, and translational clinical studies.

All manuscripts submitted to this Article Collection will undergo a full peer-review; the Guest Advisor for this Collection will not be handling the manuscripts.  

Please review the journal scope and author submission instructions prior to submitting a manuscript.  

The deadline for submitting manuscripts is September 30th, 2026. 

Please contact Menghan Li at [email protected] with any queries and discount codes regarding this Article Collection. 

Please be sure to select the appropriate Article Collection from the drop-down menu in the submission system.