Endometrial cells perceive and respond to their microenvironment forming the basis of endometrial homeostasis. Errors in endometrial cell signaling are responsible for a wide spectrum of endometrial pathologies ranging from infertility to cancer. Intensive research over the years has been decoding the sophisticated molecular means by which endometrial cells communicate to each other and with the embryo. The objective of this review is to provide the scientific community with the first overview of key endometrial cell signaling pathways operating throughout the menstrual cycle. On this basis, a comprehensive and critical assessment of the literature was performed to provide the tools for the authorship of this narrative review summarizing the pivotal components and signaling cascades operating during seven endometrial cell fate “routes”: proliferation, decidualization, implantation, migration, breakdown, regeneration, and angiogenesis. Albeit schematically presented as separate transit routes in a subway network and narrated in a distinct fashion, the majority of the time these routes overlap or occur simultaneously within endometrial cells. This review facilitates identification of novel trajectories of research in endometrial cellular communication and signaling. The meticulous study of endometrial signaling pathways potentiates both the discovery of novel therapeutic targets to tackle disease and vanguard fertility approaches.

In vitro fertilization can be an effective tool to manage the endometriosis-associated infertility, which accounts for 10% of the strategy indications. Nevertheless, a negative effect of endometriosis on IVF outcomes has been suggested. The aim of this study was to evaluate the potential effect of endometriosis in the development of embryos at cleavege stage in assisted reproduction treatment cycles. A total of 429 cycles from women previously operated for moderate/severe endometriosis were compared with 851 cycles from non-affected women. Patients were matched by age, number of oocyte retrieved and study period. A total of 3818 embryos in cleavage stage have been analyzed retrospectively. Overall, no difference was found between women with and without endometriosis regarding the number of cleavage stage embryos obtained as well as the percentage of good/fair quality embryos. Excluding cycles in which no transfers were performed or where embryos were frozen in day three, no difference was observed for blastulation rate or the percentage of good/fair blastocysts obtained. Despite similar fertilization rate and number/quality of embryos, a reduction in ongoing pregnancy rate was observed in patients affected, possibly due to an altered endometrial receptivity or to the limited value of the conventional morphological evaluation of the embryo.