Introduction, In recent years, much progress has been made in improving embryo quality and selection for transfer after in-vitro fertilization (IVF). However, despite these advances, even when embryos are considered to be of high quality using morphological and chromosomal criteria, implantation rates remain around 25–35% per embryo transfer procedure. Recently it has been demonstrated that around half of embryo transfer procedures result in implantation, but only half of these initiated implantations will result in an ongoing pregnancy. In the same study, around two-thirds of pregnancy losses were shown to occur in the immediate post-implantation period, resulting in a negative clinical pregnancy test (Figure 20.1). When considering where the ceiling on improving IVF results may lie, it is important to realize that this apparently high rate of peri-implantation failure mirrors that reported in spontaneous conceptions (Figure 20.2). Nevertheless, when implantation failure after IVF occurs, it is a cause of considerable frustration and disappointment for all concerned. Recurrent implantation failure (RIF) has been defined as three or more unsuccessful IVF cycles or the failure of conception after the replacement of 10 or more good-quality embryos. However in the age of single embryo transfer (SET), fewer patients will undergo this number of embryo transfer procedures and alternative definitions have therefore been proposed. The chance of pregnancy per cycle tends to remain stable in the first three attempts, but declines thereafter, suggesting an underlying cause for implantation failure in these patients rather than simple calculation of probability.