Endometrial Receptivity Analysis (ERA): data versus opinions

Abstract

This article summarises and contextualises the accumulated basic and clinical data on the ERA test and addresses specific comments and opinions presented by the opponent as part of an invited debate. Progress in medicine depends on new technologies and concepts that translate to practice to solve long-standing problems. In a key example, combining RNA sequencing data (transcriptomics) with artificial intelligence (AI) led to a clinical revolution in personalising disease diagnosis and fostered the concept of precision medicine. The reproductive field is no exception. Translation of endometrial transcriptomics to the clinic yielded an objective definition of the limited time period during which the maternal endometrium is receptive to an embryo, known as the window of implantation (WOI). The WOI is induced by the presence of exogenous and/or endogenous progesterone (P) after proper oestradiol (E2) priming. The window lasts 30–36 hours and, depending on the patient, occurs between LH + 6 and LH + 9 in natural cycles or between P + 4 and P + 7 in hormonal replacement therapy (HRT) cycles. In approximately 30% of IVF cycles in which embryo transfer is performed blindly, the WOI is displaced and embryo-endometrial synchrony is not achieved. Extending this application of endometrial transcriptomics, the endometrial receptivity analysis (ERA) test couples next-generation sequencing (NGS) to a computational predictor to identify transcriptomic signatures for each endometrial stage: proliferative (PRO), pre-receptive (PRE), receptive (R) and post-receptive (POST). In this way, personalised embryo transfer (pET) may be possible by synchronising embryo transfer with each patient’s WOI. Data are the only way to confront arguments sustained in opinions and/or misleading concepts; it is up to the reader to make their own conclusions regarding its clinical utility.

Comparison of the Effectiveness of Endometrial Receptivity Analysis (ERA) to Guide Personalized Embryo Transfer with Conventional Frozen Embryo Transfer in 281 Chinese Women with Recurrent Implantation Failure

“…More importantly, ERA results remain reproducible in the same individual across multiple menstrual cycles (from 29 through 40 months) as long as the body mass index (BMI), endometrial thickness, and treatment regimens are not changed during this period [ 17 ]. Previous studies have shown the effectiveness of ERA for the prediction of the WOI, and the ERA test was identified as an effective and reproducible approach to guiding pET [ 18 – 22 ]; however, the efficacy of such a tool for pET in Chinese women requires further investigation [ 23 ]. Therefore, this study aimed to compare the effectiveness of ERA-guided pET with conventional frozen embryo transfer (FET) in 281 Chinese women with RIF.…”

The Clinical Efficacy of Personalized Embryo Transfer Guided by the Endometrial Receptivity Array/Analysis on IVF/ICSI Outcomes: A Systematic Review and Meta-Analysis

“…Unfortunately, these methods of assessing the temporal boundaries of the physiologic WOI lack precision and objectivity ( Lessey, 2011 ; He et al, 2021 ). In an estimated 30% of IVF cycles where transfer of embryo is conducted blindly, displacement of WOI happens and embryo-endometrial synchrony is not attained ( Ruiz-Alonso et al, 2021 ).…”

“…Several investigations have been carried out to explore the clinical utility of pET guided by the ERA on IVF/ICSI outcomes, and to discover the rate of WOI displacement in different infertile cohort, demonstrating contradictory or conflicting results. Because of skyrocketed utilization of the ERA and the high cost for conducting ERA ( Ruiz-Alonso et al, 2021 ), the present meta-analysis aimed to determine if pET guided by the ERA improve pregnant outcomes in good-prognosis patient population (GPP, 0–2 prior failed ETs) and recurrent implantation failure (RIF)/poor-prognosis patient cohort separately. The secondary objective was to estimate the prevalence of displaced WOI in above two infertile population.…”

Identifying women with a narrow window of embryo implantation using the endometrial receptivity assay

“…Recurrent implantation failure (RIF) is defined as the failure of high quality embryos to implant after several ART cycles. The endometrial receptivity assay (ERA: Igenomix, Miami, FL) was an attempt to determine the optimal WOI by defining the transcriptomic signature for endometrial receptivity [8] . Such a test potentially provides a rational basis for evaluating and treating RIF [8][9][10] .…”

“…The endometrial receptivity assay (ERA: Igenomix, Miami, FL) was an attempt to determine the optimal WOI by defining the transcriptomic signature for endometrial receptivity [8] . Such a test potentially provides a rational basis for evaluating and treating RIF [8][9][10] . The ERA was originally designed to evaluate the expression of 238 genes based on mRNA in tissue obtained from a timed endometrial biopsy taken 120 hours after the addition of progesterone in a woman with an estrogen primed endometrium.…”