"Recurrent implantation failure - It's time to get personal"
Recurrent implantation failure (RIF) is a controversial and poorly understood diagnostic dilemma. It can be defined as a failed embryo implantation, where b-human chorionic gonadotropin is in the negative range after a certain number of embryo transfers. The term ''implantation failure'' should be reserved for this specific scenario rather than for early failed biochemical pregnancies that may have a different underlying etiology. Although the concept of recurrence clearly implies repeated failed embryo implantation, the precise number of failed transfers to be classified as RIF is not well established. It is apparent that a cleavage-stage embryo produced by a 45-year-old woman would have a drastically different chance of implantation compared with a top-quality blastocyst from a 32-year-old woman. Therefore, a simple number of failed transfer attempts, without incorporating individual patient and embryo characteristics, is likely to grossly exaggerate the prevalence of RIF, especially in older adults and patients with poor prognosis. This overestimation of the true prevalence of RIF has serious consequences that hamper future research efforts and, most importantly, result in patients and clinicians utilizing unproven and mostly unnecessary tests and interventions, of which some may be detrimental to the overall chance of pregnancy.
The basic question that must be asked is ''after how many transfers is a recurrent failure to implant more likely due to some unrecognized underlying pathology, rather than chance alone?'' In the issue of the journal Fertility and Sterility, Ata et al. pose this crucial question and endeavor to answer it on the basis of an embryo's euploidy status. They postulate that the diagnosis of RIF should be made once recurrent failure of embryos to implant is unlikely to be due to embryo aneuploidy. They use the concept of ''cumulative implantation probability,'' which is similar to the one we proposed recently, termed ''theoretical cumulative implantation rate''. The basic concept behind their model is rather elegant in its simplicity: if 50% of embryos at a certain female age are euploid and a euploid embryo has a 50% chance of implantation, then it follows that an untested embryo produced at this age has a 25% chance of implantation. The next step in their model is to estimate how many embryos with this probability of implantation would be required (cumulative implantation probability) to achieve a certain threshold, beyond which RIF can be diagnosed.
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