Nonreceptive endometrial receptivity assay result did not predict failed implantation: a nested non-selection study within a randomized clinical trial

To evaluate the performance of the endometrial receptivity assay (ERA) as a clinical diagnostic test. The control arm of the Synchrony trial served as an a priori non-selection prospective cohort study, since the ERA was performed in both the control and intervention groups, but no intervention was made in the control group. Using these data, the sensitivity, specificity, negative and positive predictive values (NPV, PPV) and other markers were calculated. The primary outcome was sustained implantation of euploid blastocysts (clinical pregnancy with fetal heart rate). A sensitivity analysis was also conducted, comparing patients with a nonreceptive ERA defined as recommending ≥ 24 hours change in progesterone exposure, with changes ≤12 hours considered normal. There were no differences in the clinical outcomes between the control and interventions arms of the clinical trial, nor in sensitivity analyses (Table 1). The sensitivity and specificity of the ERA to predict failure of sustained embryo implantation were poor (55% and 49% respectively). The ERA had a PPV of 74 and 78% in both models, but extremely poor NPV of 29%. Positive and negative likelihood ratios were also low in both analyses. Receiver operating characteristic (ROC) results demonstrated an area under curve (AUC) of 0.52.Tabled 1Receptive vs Nonreceptive1 (Primary Analysis)Receptive or Nonreceptive2 (Sensitivity Analysis)Clinical OutcomeReceptive (n=208)Nonreceptive (n=178)P valueReceptive(n=120)Nonreceptive(n=266)P valuePositive hCG (%)167 (80.3)140 (78.7)0.78799 (82.5)208 (78.2)0.404Sustained implantation (%)155 (74.5)126 (70.8)0.48094 (78.3)187 (70.3)0.129Clinical pregnancy loss (%)25 (12)16 (9)0.42518 (15)23 (8.6)0.090Live birth130 (62.5)109 (61.2)0.88176 (63.3)163 (61.3)0.786Statistical OutcomeReceptive vs Nonreceptive1 (Primary Analysis)Receptive or Nonreceptive2 (Sensitivity Analysis)Sensitivity55.2%33.5%Specificity49.5%75.2%Positive predictive value74.5%78.3%Negative predictive value29.2%29.7%Positive likelihood ratio1.091.35Negative likelihood ratio0.910.88ROC AUC0.520.541Nonreceptive: any result recommending ≥12 hours progesterone change2Nonreceptive: any result recommending ≥24 hours progesterone change Open table in a new tab 1Nonreceptive: any result recommending ≥12 hours progesterone change 2Nonreceptive: any result recommending ≥24 hours progesterone change ERA thresholds of both 12- and 24- hour displacement demonstrated poor diagnostic performance for predicting failure to achieve sustained implantation, with a negative predictive value of only 29%. Furthermore, likelihood ratios demonstrated the test to be highly unlikely to change clinical management or outcomes.