A new definition of recurrent implantation failure on the basis of anticipated blastocyst aneuploidy rates across female age

Abstract

Objective: To present a definition of recurrent implantation failure that accounts for the effects of female age and anticipated blastocyst euploidy rates on cumulative implantation rates.

Design: Mathematical modeling.

Setting: Not applicable.

Patient(s): Not applicable.

Intervention(s): Mathematical modeling of cumulative implantation probability on the basis of published blastocyst euploidy rates across categories of female age.

Main outcome measure(s): The number of blastocysts required to achieve 95% cumulative implantation probability under the assumption of the absence of any other factor affecting implantation.

Result(s): When the euploidy status of the transferred embryo is unknown (i.e., not subjected to preimplantation genetic testing for aneuploidies), our simulation shows that no age category reaches 95% cumulative probability of implantation of at least one embryo until after transfer of seven blastocysts. The number of blastocysts required to reach the same threshold is higher for older patients. For example, women older than 38 years require transfer of more than 10 untested blastocysts for the upper range of predictive probability to meet the threshold of 95%. On the other hand, if the implantation rate for a euploid blastocyst is assumed to be 55%, then 4 blastocysts are enough to reach a cumulative probability rate greater than 95%, regardless of age.

Conclusion(s): The term "recurrent implantation failure" should be a functional term guiding further management. We suggest that recurrent implantation failure should not be called until implantation failure becomes reasonably likely to be caused by factors other than embryo aneuploidy, the leading cause of implantation failure. We propose a new definition that factors in anticipated blastocyst euploidy rates across categories of female age, euploid blastocyst implantation rate, and a specified threshold of cumulative probability of implantation.

Keywords: ART failure; aneuploidy; euploid embryo; genetic diagnosis; miscarriage; preimplantation.