Repeated implantation failure at the crossroad between statistics, clinics and over-diagnosis

The most common definition of repeated implantation failure (RIF) is the failure to obtain a clinical pregnancy after three completed IVF cycles. This definition, however, may lead to misuse of the diagnosis. To disentangle this, we set up a mathematical model based on the following main assumptions: rate of success of IVF constant and set at 30%; and RIF postulated to be a dichotomous condition (yes or no) with a prevalence of 10%. On this basis, the expected cumulative chance of pregnancy after three and six cycles was 59% and 79%, respectively. Consequently, the false–positive rate of a diagnosis of RIF is 75% and 51%, respectively. Increasing the rate of success of IVF or the prevalence of RIF lowers but does not make unremarkable the rate of false–positive diagnoses. Overall, this model shows that the commonly used definition of RIF based on three failed attempts in a standard population with good prognosis leads to over-diagnosis and, potentially, to over-treatments.