Objective: The aim of the study was to propose a set of tests to clarify the diagnosis of repeated implantation failure in patients undergoing in vitro fertilization (IVF). Study design: Fifty-nine patients with at least two unsuccessful IVF attempts were included in the study. Blood samples were evaluated for the presence of underlying thyroid abnormalities, antiphospholipid antibodies (aPL), increased levels of natural killer cells (NK), inherited thrombophilia and mouse embryo assay factor (MEAf). The same tests were performed on 20 normal fertile control patients. Results: Seventy-six percent of IVF patients showed at least one abnormal result. This incidence was higher with respect to that found among control patients (45% ). The prevalence of thyroid abnormalities, aPL and increased NK level was higher in IVF patients whereas no differences were observed in terms of prevalence of inherited thrombophilias and MEAf. Conclusions: A better understanding of reproductive failure mechanisms should allow an effective diagnostic flow chart and a focused therapeutic option for patients experiencing repeated IVF failure. With this objective in mind, our data provide two important results: thyroid abnormalities, aPL and increased NK levels are more prevalent in women experiencing IVF failure. No evidence was found for an association between inherited thrombophilia and MEAf and failure to achieve pregnancy after IVF. Objective: The aim of the study was to propose a set of tests to clarify the diagnosis of repeated implantation failure in patients undergoing in vitro fertilization (IVF). Study design: Fifty-nine patients with at least two unsuccessful IVF attempts were included in the study. Blood samples were evaluated for the presence of underlying thyroid abnormalities, antiphospholipid antibodies (aPL), increased levels of natural killer cells (NK), inherited thrombophilia and mouse embryo assay factor (MEAf). The same tests were performed on 20 normal fertile The incidence was higher with respect to that found among control patients (45%). The prevalence of thyroid abnormalities, aPL and increased NK level was higher in IVF patients and no differences were observed in terms of prevalence of inherited thrombophilias and MEAf. Conclusions: A better understanding of reproductive failure mechani With this objective in mind, our data provide two important results: thyroid abnormalities, aPL and increased NK levels are more prevalent in women experiencing IVF failure. No evidence was found for an association between inherited thrombophilia and MEAf and failure to achieve pregnancy after IVF.