Abstract Study question The discordance or consistency between mRNA and microRNA profiles for endometrial receptivity tests (ERT) and associated clinical factors deserve further elucidation. Summary answer The discordance between mRNA and microRNA profiles for ERT existed substantially for patients with recurrent implantation failure and was affected by endometriosis or endometrial polyps. What is known already Evaluation of endometrial receptivity in ART cycles includes mRNA and microRNA approaches. Both ways differentiate the receptive from the nonreceptive endometrium by the gene expression profiles identified from the biopsied endometrial tissue. Nonetheless, the discordance or consistency between these two approaches has not been investigated. Furthermore, gene expression profiles are affected by several clinical factors, such as age, endometritis, or even endometriosis. Whether these clinical factors contribute to the ERT results also needs further investigation. Study design, size, duration A prospective cross-sectional study with 100 infertile couples with recurrent implantation failure from August 2021 to July 2023. Participants/materials, setting, methods We recruited 100 infertile women with recurrent implantation failure who will undergo endometrial biopsy and evaluation of receptivity using the mRNA profiles, namely endometrial receptivity assay (ERA), at Lee Women’s Hospital, Taichung, Taiwan. The miRNA profile of the collected endometrial tissue was evaluated with MIRA (MicroRNA-based Endometrial Receptivity Analysis). The study protocol was approved by the IRB committee of Chung Shan Medical University Hospital (CSMUH No: CS2-21001). Main results and the role of chance According to the criteria of the corresponding company, ERA and MIRA determined that the endometrium was pro-receptive, receptive, or post-receptive. However, only 72% of the 100 participants showed consistent results. The Kappa statistics are only 0.50 (95% CI 0.34-0.66). In the 28 participants with discordant MIRA and ERA results, 9 (9/28= 32.1%), 14 (13/28 = 50%), and 5 (5/28 = 17.9%) patients had pre-receptive, receptive, and post-receptive ERA results, respectively. Interestingly, those patients with pre-receptive ERA characterized a higher percentage of endometriosis or endometrial polyps compared to those patients with receptive and post-receptive ERA results (5/9=55.6% vs. 3/14=21.4% vs. 0/5 = 0% for endometriosis, p = 0.016; 7/9 = 77.8% vs 4/14 =28.6% vs. 1/5 = 20%, p = 0.035, Kai square test, for endometrial polyps). Limitations, reasons for caution The samples of discordant ERA and MIRA are too small. We didn’t have the raw data about ERA, even though the raw data about MIRA are available. We couldn’t do further bioinformatic analysis to identify the molecular signaling pathway. Wider implications of the findings ERA or MIRA for evaluating endometrial receptivity requires careful interpretation of the results, especially in patients with benign endometrial lesions, such as endometriosis or endometrial polyps. The gene expression profiles regarding the progesterone-progesterone receptor signaling pathway may be altered in these patients, leading to misinterpretation of ERT results. Trial registration number not applicable