Clinical utility of the endometrial receptivity analysis in women with prior failed transfers

Purpose To determine the utility of the endometrial receptivity analysis (ERA) in women with prior failed embryo transfers (ET).

This was a retrospective study of patients who underwent an ERA test with a subsequent frozen ET. Women were classified based on their indication for an ERA test: (1) ≥ 1 prior failed ET (cases), or (2) as a prophylactic measure (controls). A subset analysis of women with ≥ 3 prior failed transfers was performed. Pregnancy outcomes of the subsequent cycle were examined, including conception, clinical pregnancy, and ongoing pregnancy/live birth.

A total of 222 women were included, 131 (59%) women with ≥ 1 prior failed ET and 91 (41%) controls. Among the 131 women with ≥ 1 prior failed ET, 20 women (9%) had ≥ 3 prior failed ETs. The proportion of non-receptive ERA tests in the three groups were the following: 45% (≥ 1 prior failed ET), 40% (≥ 3 prior failed ETs), and 52% (controls). The results did not differ between cases and controls. The pregnancy outcomes did not differ between women with ≥ 1 prior failed ET and controls. In women with ≥ 3 prior failed ETs, there was a lower ongoing pregnancy/live birth rate (28% vs 54%, P = 0.046).

Women with ≥ 1 prior failed ET and ≥ 3 prior failed ETs had a similar prevalence of non-receptive endometrium compared to controls. Women with ≥ 3 prior failed ETs had a lower ongoing pregnancy/live birth rate despite a personalized FET, suggesting that there are additional factors in implantation failure beyond an adjustment in progesterone exposure. Similar content being viewed by others

Lessey BA. Assessment of endometrial receptivity. Fertil Steril. 2011;96:522–9. Achache H, Revel A. Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006;12:731–46. Craciunas L, Gallos I, Chu J, Bourne T, Quenby S, Brosens JJ, et al. Conventional and modern markers of endometrial receptivity: a systematic review and meta-analysis. Hum Reprod Update. 2019;25:202–23. Aghajanova L, Hamilton AE, Giudice LC. Uterine receptivity to human embryonic implantation: histology, biomarkers, and transcriptomics. Semin Cell Dev Biol. 2008;19:204–11. Coutifaris C, Myers ER, Guzick DS, Diamond MP, Carson SA, Legro RS, et al. Histological dating of timed endometrial biopsy tissue is not related to fertility status. Fertil Steril. 2004;82:1264–72. Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, et al. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007;148:3814–26. Savaris RF, Groll JM, Young SL, DeMayo FJ, Jeong JW, Hamilton AE, et al. Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles. J Clin Endocrinol Metab. 2011;96:1737–46. Kao LC, Germeyer A, Tulac S, Lobo S, Yang JP, Taylor RN, et al. Expression profiling of endometrium from women with endometriosis reveals candidate genes for disease-based implantation failure and infertility. Endocrinology. 2003;144:2870–81. Tamaresis JS, Irwin JC, Goldfien GA, Rabban JT, Burney RO, Nezhat C, et al. Molecular classification of endometriosis and disease stage using high-dimensional genomic data. Endocrinology. 2014;155:4986–99. Kao LC, Tulac S, Lobo S, Imani B, Yang JP, Germeyer A, et al. Global gene profiling in human endometrium during the window of implantation. Endocrinology. 2002;143:2119–38. Talbi S, Hamilton AE, Vo KC, Tulac S, Overgaard MT, Dosiou C, et al. Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women. Endocrinology. 2006;147:1097–121. Ruiz-Alonso M, Blesa D, Simon C. The genomics of the human endometrium. Biochim Biophys Acta. 2012;1822:1931–42. Garrido-Gomez T, Ruiz-Alonso M, Blesa D, Diaz-Gimeno P, Vilella F, Simon C. Profiling the gene signature of endometrial receptivity: clinical results. Fertil Steril. 2013;99:1078–85. Gomez E, Ruiz-Alonso M, Miravet J, Simon C. Human endometrial transcriptomics: implications for embryonic implantation. Cold Spring Harb Perspect Med. 2015;5:a022996. Díaz-Gimeno P, Horcajadas JA, Martinez-Conejero JA, Esteban FJ, Alama P, Pellicer A, et al. A genomic diagnostic tool for human endometrial receptivity based on the transcriptomic signature. Fertil Steril. 2011;95:50–60. Endometrial Receptivity Analysis. Available at: http://www.igenomix.com/genetic-solutions/era-endometrial-receptivity-analysis/. Accessed March 5, 2020. Díaz-Gimeno P, Ruiz-Alonso M, Blesa D, Bosch N, Martinez-Conejero JA, Alama P, et al. The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity. Fertil Steril. 2013;99:508–17. Cho K, Tan S, Buckett W, Dahan MH. Intra-patient variability in the endometrial receptivity assay (ERA) test. J Assist Reprod Genet. 2018;35:929–30. Ruiz-Alonso M, Blesa D, Díaz-Gimeno P, Gómez E, Fernández-Sánchez M, Carranza F, et al. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013;100:818–24. Ruiz-Alonso M, Galindo N, Pellicer A, Simon C. What a difference two days make: “personalized” embryo transfer (pET) paradigm: a case report and pilot study. Hum Reprod. 2014;29:1244–7. Tan J, Kan A, Hitkari J, Taylor B, Tallon N, Warraich G, et al. The role of the endometrial receptivity array (ERA) in patients who have failed euploid embryo transfers. J Assist Reprod Genet. 2018;35:683–92. Bassil R, Casper R, Samara N, Hsieh TB, Barzilay E, Orvieto R, et al. Does the endometrial receptivity array really provide personalized embryo transfer? J Assist Reprod Genet. 2018;35:1301–5. Neves AR, Devesa M, Martinez F, Garcia-Martinez S, Rodriguez I, Polyzos NP, et al. What is the clinical impact of the endometrial receptivity array in PGT-A and oocyte donation cycles? J Assist Reprod Genet. 2019;36:1901–8. Hashimoto T, Koizumi M, Doshida M, Toya M, Sagara E, Oka N, et al. Efficacy of the endometrial receptivity array for repeated implantation failure in Japan: a retrospective, two-centers study. Reprod Med Biol. 2017;16:290–6. Mahajan N. Endometrial receptivity array: clinical application. J Hum Reprod Sci. 2015;8:121–9. Patel JA, Patel AJ, Banker JM, Shah SI, Banker MR. Personalized embryo transfer helps in improving in vitro fertilization/ICSI outcomes in patients with recurrent implantation failure. J Hum Reprod Sci. 2019;12:59–66. Lensen S, Shreeve N, Barnhart KT, Gibreel A, Ng EHY, Moffett A. In vitro fertilization add-ons for the endometrium: it doesn’t add up. Fertil Steril. 2019;112:987–93. Tan BK, Vandekerckhove P, Kennedy R, Keay SD. Investigation and current management of recurrent IVF treatment failure in the UK. BJOG. 2005;112(6):773–80. Margalioth EJ, Ben-Chetrit A, Gal M, Eldar-Geva T. Investigation and treatment of repeated implantation failure following IVF-ET. Hum Reprod. 2006;21(12):3036–43. Stephenson MD, Fluker MR. Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial. Fertil Steril. 2000;74(6):1108–13. Author information Authors and Affiliations Corresponding author Ethics declarations Conflict of interest Dr. Jessica Chan is a scientific advisor for the women’s health start up BINTO. All other authors declare that they have no conflict of interest. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions About this article Cite this article Eisman, L.E., Pisarska, M.D., Wertheimer, S. et al. Clinical utility of the endometrial receptivity analysis in women with prior failed transfers. J Assist Reprod Genet 38, 645–650 (2021). https://doi.org/10.1007/s10815-020-02041-9 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-020-02041-9