Endometrial fluid biomarkers and their potential as predictors of successful embryo implantation

BACKGROUND: Embryo implantation is a complex biological process which requires synchronized dialogue between the receptive endometrium and the blastocyst. The endometrium, however, is only receptive to embryo implantation for a very short period. Recurrent implantation failure (RIF) is a major challenge in assisted reproductive techniques mainly due to impaired receptivity, but there is still a need for a reliable and valid clinical test to assess endometrial receptiveness, especially at embryo transfer time. The aim of this review is to investigate what is currently known about the contribution of endometrial fluid (EF) to endometrial receptivity by identifying its potential biomarkers. METHODS: This study involved an extensive search of the electronic databases PubMed and Cochrane, covering the period from 2011 to 2022. A combination of Medical Subject Headings with the terms ‘endometrial fluid’ and ‘embryo implantation’ was used. RESULTS: Several different proteins presented in the endometrial cavity fluid have been described but the most consistent as potential biomarkers were Proprotein Convertase 6 (PC6), Vascular Endothelial Growth Factor (VEGF), PIGF (Placental growth factor), β3 integrin, Colony Stimulating Factor-3 (CSF-3), Leukaemia inhibitory factor (LIF), glycodelin and extracellular vesicles (EVs). CONCLUSIONS: Strong indicators support the use of uterine fluid collection as a non-invasive tool for receptivity assessment. Therefore, it could improve outcomes of assisted reproductive techniques.