Oocyte fertilization rates in bovines following artificial insemination or natural mating are generally good (~90%). Curiously, only about one third of these pregnancies remain until 30 days post-AI in dairy cows. Thus, most pregnancies are lost between fertilization and early embryonic growth. Although classical pathways describing that lower progesterone post-AI is the main culprit to these early embryonic losses, a number of environmental factors such as heat-stress as well as novel concepts in bovine physiology including the effects of excessive negative energy balanced (NEB) and the insulin-resistant state experienced by high producing cows during the postpartum period can help explain the poor reproductive performance, generally observed in dairy herds world-wide. Thus, expanding the scientific knowledge in these critical areas in bovine fertility related to the evident impact of NEB and/or altered circulating and uterine metabolites in the postpartum period on oocyte quality, gamete transport, uterine environment, and early embryonic growth are of major importance to improve reproductive efficiency in modern high producing dairy cows.