The Rate of True Recurrent Implantation Failure (RIF) Is Low: Results of Three Successive Frozen Euploid Single Embryo Transfers (FE-SET)

Abstract

OBJECTIVE: To determine the true prevalence of recurrent implantation failure (RIF). DESIGN Retrospective cohort study METHODS: Women (n=4,429) with anatomically normal uterus who underwent up to three consecutive euploid frozen SETs were included in the study. Cycles with donor eggs or gestational carriers were excluded. Cumulative outcomes from these cycles were analyzed. A logistic regression model was employed to assess the differences of outcomes between first, second, and third euploid SET and a Kaplan-Meier curve as utilized to analyze cumulative implantation rate. RESULTS: The mean age of the patients included in the study was of 35.4±4.2 years. The sustained implantation rates (SIR) of the 1 st , 2 nd and 3 rd FE-SET were 69.9%, 59.8%, and 60.3% per transfer, respectively. The cumulative SIR after up to 3 consecutive FE-SET was 95.2% (95% CI: 94.0%-96.2%). The live birth rates (LBRs) after the 1 st , 2 nd and 3 rd FE-SET were 64.8%, 54.4%, and 54.1% per transfer, respectively. The cumulative LBR after up to 3 consecutive FE-SET was 92.6% (95% CI: 91.2%-93.9%). The miscarriage rate after observing a positive heartbeat was not different between the 1 st (7.2%, 95%CI: 6.4%-8.2%), 2 nd (8.8%, 95% CI:6.3%-11.7%) and 3 rd (12.7%, 95%CI: 6.2%-22.0%) FE-SET. CONCLUSIONS: Our findings suggest that true RIF is rare. For those patients with the ability to make euploid blastocysts, less than 5% would fail to achieve a clinical pregnancy with 3 embryos transferred. It remains to be further investigated whether this threshold identifies a truly recalcitrant group, or simply a statistical certainty based on random variation. FUNDING STATEMENT: All funding was internal from one program – RMA New Jersey, Basking Ridge, US. No outside funding was provided, thus no commercial interest for anyone involved. RMA New Jersey does not collect any money for the performance of PGT-A and thus does not resale or profit from it. Patients were not charged for PGT-A screening. DECLARATION OF INTERESTS: E.S. is a consultant for and receives research funding from the Foundation for Embryonic Competence; he is co-founder and a shareholder of ACIS. All other authors have no competing interests to disclose. ETHICS APPROVAL STATEMENT: No embryos were biopsied specifically for the purpose of this study. Given the retrospective nature of this study, the access and processing of patient data was approved by the Advarra Institutional Review Board under a protocol for retrospective studies - protocol number Pro00027158.