Is there a treatable cause of repeated implantation failure, or is it simply treatment failure by chance?

Research question: Does repeated implantation failure (RIF) sometimes have a cause, or is it simply treatment failure by chance? Design: A hypothetical model of a cohort of 1000 women undergoing four repeated IVF attempts was constructed. A proportion of women with RIF carried an underlying risk factor negatively affecting implantation, compared with women without the factor. In strategy A, women had standard IVF without additional treatment; in strategy B, the women received standard IVF plus an additional treatment. The sensitivity analysis varied the prevalence of the underlying risk factor from 5% to 50%. The model was compared with literature studies where a treatment strategy had been applied. Results: With strategy A, the clinical pregnancy rate decreased with subsequent IVF attempts (31% in the fi rst transfer with a risk factor prevalence of 5%, to 8% in the fourth transfer with a risk factor prevalence of 50%). As the prevalence increased, the clinical pregnancy rate was higher with strategy A. For strategy B, the clinical pregnancy rates for the modelled cohort decreased with each subsequent IVF attempt. Regardless of the prevalence of the risk factor, the decline in clinical pregnancy rate was less strong (from 32% in the fi rst transfer with a prevalence of 5%, to 25% in the fourth transfer with a prevalence of 50%). When applying the model to the literature studies, the trends expected for strategy B (decreasing clinical pregnancy rates) were not expressed. Conclusions: RIF might therefore be of iatrogenic origin due to the low success rate of IVF and might be triggered by the increasing female age associated with higher numbers of RIF.