How common is real repeated implantation failure? An indirect estimate of the prevalence

Research question: What is the real prevalence of repeated implantation failure (RIF) and what reliable estimates can be given on the risk of false-positive diagnosis after two or three failed IVF attempts. Design: A recent theoretical model suggested that commonly used definitions (two or three failed IVF attempts in good-prognosis couples) may expose couples to substantial odds of overdiagnosis and overtreatment. This model, however, was theoretical and based on unproven assumptions that the pregnancy rate in the non-RIF population was 30% and the prevalence of RIF was 10%. In the present study, we applied this model to real data to distinguish the real prevalence of RIF and to provide more reliable estimates on the risk of false-positive diagnosis after two or three failed IVF attempts. To this aim, we retrospectively selected 1221 good-prognosis couples and evaluated pregnancy rates up to the third cycle. Results: The clinical pregnancy rate at first, second and third IVF cycle was 52%, 41% and 28%, respectively. A pregnancy rate of 61% was extrapolated in the non-RIF population and 15% among women who had experienced RIF. Therefore, the rate of false-positive diagnoses of RIF after two, three and six failed cycles would be 46%, 25%, and 2%, respectively. Conclusions: Our analyses show that estimated prevalence of RIF is 15%. The frequently used definition of RIF based on three failed attempts (but not two) in good-prognosis couples seems justified. Physicians, however, should bear in mind that couples may be inappropriately labelled with this condition in one out of four cases.