In the U.S., about 12% of women have impaired fecundity and 7% of couples have infertility, with 1/3 attributable to female factors. Underlying mechanisms remain largely unknown, even when more proximal pathologies (e.g., endometriosis) are identified, thus precluding the development of accurate diagnostics and personalized therapies. In addition, pregnancies in subfertile women, conceived naturally or as a result of infertility treatments, have greater risk of complications such as pre-eclampsia, preterm birth, and fetal growth restriction that have life-long effects on the offspring. Thus, dissecting the mechanisms underlying reproductive success and compromise at the genomic, molecular, and cellular levels is crucial to the health and well-being of this and future generations. Engaging investigators from multiple disciplines and building a sustainable pipeline of junior investigators, including those underrepresented in science and medicine, is also essential to this effort, as is the promotion of public literacy about reproductive health and science. These are core principles of our NIH National Center for Translational Research in Reproduction and Infertility (NCTRI) at UCSF funded since 2007. It currently is focused on the inter-related roles of endometrial inflammation, epigenetics, and developmental processes of the peri-implantation uterus and early conceptus as central determinants of early pregnancy success or failure. This focus is motivated by the fact that the clinical association between pathological endometrial inflammation and female infertility, while well-established, lacks a deep mechanistic understanding.