Extracellular vesicles (EVs) released by endometrium into the uterine fluid are emerging as an important mediator of intercellular communication between mother and the embryo. Here, we show that these EVs are dynamically regulated for their protein composition during the natural menstrual cycle, and transfer invasive properties and antioxidant function to trophectoderm cells. These EVs carry proteins that regulate embryo implantation and predict window of implantation, thus highlighting their potential as a minimally invasive biomarker. Clinical applications could include use of nanoparticles engineered to contain the most relevant proteins and delivered at the time of embryo transfer, to improve implantation success. Alternatively, it could be applied to the development of a new class of non-steroidal once-a month contraceptive.