Pregnancy failure occurs at different stages for a variety of causes with major impacts on reproductive and economic performance of cattle operations. Four pivotal periods during the first trimester of pregnancy are discussed. The first period occurs in the first week of pregnancy with lack of fertilization and degeneration of the early embryo producing major losses, particularly under specific environmental and hormonal conditions. In general, 20–50% of high-producing lactating dairy cows have already experienced pregnancy loss during the first week though there are some methods available to decrease pregnancy loss during this period. These involve increasing oocyte quality by methods such as decreasing heat stress, increasing progesterone concentrations during preovulatory follicle development, and reducing loss of body condition during the early postpartum period. Additionally, the effect of the oviductal environment on early embryonic development is an area of active investigation. The second pivotal period (d 8–27) encompasses embryo elongation and maintenance of the corpus luteum (CL) by maternal signals. There is surprising variation in reported losses during this period with insufficient or inappropriate timing of embryonic interferon-tau or inadequate uterine histotroph as underlying causes of ~30% losses. The third pivotal period is during the second month of pregnancy (d 28 to 60) with losses averaging 11.7% in US dairy cows with ~40% greater losses in multiparous (13.4%) than primiparous (9.5%) cows. Recipients of in vitro produced embryos undergo greater losses (15.6%) in second month. Finally, a fourth pivotal period during the third month of pregnancy has lower pregnancy losses (~2%), compared with the first 3 periods. Twins in the same uterine horn can be an important cause of pregnancy loss in second and third months. Nevertheless, conclusive determination of underlying causes of most pregnancy losses remains elusive. Each pivotal period corresponds to physiological changes in the embryo, uterine environment, and ovary that may allow development of strategies that rationally target the fundamental reason for pregnancy loss in each pivotal period