{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:45Z","timestamp":1787028645157,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T00:00:00Z","timestamp":1712534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Recurrent implantation failure (RIF) poses a significant challenge in assisted reproductive technology (ART) outcomes. The endometrium plays a crucial role in embryo implantation, and its protein expression profile is integral in determining receptivity. Proteomics has emerged as a valuable tool in unraveling the molecular intricacies underlying endometrial receptivity and RIF. The aim of the present review is to analyze the contribution of proteomics to the understanding of endometrial protein expression in women with RIF, based on the results of significant proteomic studies. Medline\/Pubmed databases were searched using keywords pertaining to proteomics combined with terms related to RIF. 15 studies were included in the present review. Several proteins have been found to exbibit differential expression in endometrial biopsies and fluid samples between fertile women and women with RIF during the receptive endometrial phase. The profile of endometrial proteins varied significantly among the studies. Nevertheless, similar changes in the expression levels of annexin-6, progesterone receptor, MMP-2, and MMP-9 in the endometrium of women with RIF, were found in more than one study indicating that certain proteins could potentially be effective biomarkers of endometrial receptivity. Proteomics contributes significantly to the understanding of protein expression in the endometrium of women with RIF and the analysis of proteins in endometrial fluid are promising for improving the clinical management of RIF.<\/jats:p>","DOI":"10.3390\/jcm13072145","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T09:31:23Z","timestamp":1712568683000},"page":"2145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["The Contribution of Proteomics in Understanding Endometrial Protein Expression in Women with Recurrent Implantation Failure"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7716-1521","authenticated-orcid":false,"given":"Anastasios","family":"Potiris","sequence":"first","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Alyfanti","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirini","family":"Drakaki","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Medical School, Alexandra Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Mavrogianni","sequence":"additional","affiliation":[{"name":"First Department of Obstetrics and Gynecology, Medical School, Alexandra Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodoros","family":"Karampitsakos","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavlos","family":"Machairoudias","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Topis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Zikopoulos","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Royal Cornwall Hospital, Treliske, Truro TR1 3LQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chara","family":"Skentou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Medical School of the University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Periklis","family":"Panagopoulos","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Drakakis","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofoklis","family":"Stavros","sequence":"additional","affiliation":[{"name":"Third Department of Obstetrics and Gynecology, Medical School, University General Hospital \u201cATTIKON\u201d, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.rbmo.2019.10.014","article-title":"How common is real repeated implantation failure? An indirect estimate of the prevalence","volume":"40","author":"Busnelli","year":"2020","journal-title":"Reprod. Biomed. Online"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rbmo.2013.08.011","article-title":"Recurrent implantation failure: Definition and management","volume":"28","author":"Coughlan","year":"2014","journal-title":"Reprod. Biomed. Online"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"hoad023","DOI":"10.1093\/hropen\/hoad023","article-title":"ESHRE good practice recommendations on recurrent implantation failure","volume":"2023","author":"Cimadomo","year":"2023","journal-title":"Hum. Reprod. Open"},{"key":"ref_4","first-page":"8895","article-title":"The association between endometrial polyps, chronic endometritis, and IVF outcomes","volume":"27","author":"Vaduva","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1007\/s10815-020-01955-8","article-title":"Chronic endometritis and altered embryo implantation: A unified pathophysiological theory from a literature systematic review","volume":"37","author":"Buzzaccarini","year":"2020","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102347","DOI":"10.1016\/j.bpobgyn.2023.102347","article-title":"Effects of endocrine disrupting compounds on female fertility","volume":"88","author":"Panagopoulos","year":"2023","journal-title":"Best Pract. Res. Clin. Obstet. Gynaecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1061766","DOI":"10.3389\/fendo.2022.1061766","article-title":"Recurrent implantation failure: A comprehensive summary from etiology to treatment","volume":"13","author":"Ma","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Potiris, A., Perros, P., Drakaki, E., Mavrogianni, D., Machairiotis, N., Sfakianakis, A., Karampitsakos, T., Vrachnis, D., Antonakopoulos, N., and Panagopoulos, P. (2024). Investigating the Association of Assisted Reproduction Techniques and Adverse Perinatal Outcomes. J. Clin. Med., 13.","DOI":"10.3390\/jcm13020328"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1093\/humupd\/dmy044","article-title":"Conventional and modern markers of endometrial receptivity: A systematic review and meta-analysis","volume":"25","author":"Craciunas","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/chromsci\/bmw167","article-title":"Proteomics: Technologies and Their Applications","volume":"55","author":"Aslam","year":"2017","journal-title":"J. Chromatogr. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1093\/humupd\/dmz042","article-title":"Identifying biomarkers for predicting successful embryo implantation: Applying single to multi-OMICs to improve reproductive outcomes","volume":"26","author":"Munoz","year":"2020","journal-title":"Hum. Reprod. Update"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/molehr\/gap108","article-title":"Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis","volume":"16","author":"Brosens","year":"2010","journal-title":"Mol. Hum. Reprod."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1093\/humrep\/des134","article-title":"Expression of leukaemia inhibitory factor and interleukin 15 in endometrium of women with recurrent implantation failure after IVF; correlation with the number of endometrial natural killer cells","volume":"27","author":"Mariee","year":"2012","journal-title":"Hum. Reprod."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1093\/humrep\/deu171","article-title":"Deciphering the proteomic signature of human endometrial receptivity","volume":"29","author":"Quinonero","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"gmr.15027849","DOI":"10.4238\/gmr.15027849","article-title":"Endometrial expression of telomerase, progesterone, and estrogen receptors during the implantation window in patients with recurrent implantation failure","volume":"15","author":"Long","year":"2016","journal-title":"Genet. Mol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.rbmo.2018.11.022","article-title":"Endometrial stromal cell proteome mapping in repeated implantation failure and recurrent pregnancy loss cases and fertile women","volume":"38","author":"Dhaenens","year":"2019","journal-title":"Reprod. Biomed. Online"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Bielfeld, A.P., Pour, S.J., Poschmann, G., Stuhler, K., Krussel, J.S., and Baston-Bust, D.M. (2019). A Proteome Approach Reveals Differences between Fertile Women and Patients with Repeated Implantation Failure on Endometrial Level(-) Does hCG Render the Endometrium of RIF Patients?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020425"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e11009","DOI":"10.7717\/peerj.11009","article-title":"Screening and identification of endometrial proteins as novel potential biomarkers for repeated implantation failure","volume":"9","author":"Wang","year":"2021","journal-title":"PeerJ"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Fu, H., Tan, W., Chen, Z., Ye, Z., Duan, Y., Huang, J., Qi, H., and Liu, X. (2022). TOP2A deficit-induced abnormal decidualization leads to recurrent implantation failure via the NF-kappaB signaling pathway. Reprod. Biol. Endocrinol., 20.","DOI":"10.1186\/s12958-022-01013-1"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1144393","DOI":"10.3389\/fendo.2023.1144393","article-title":"Endometrial proteomic profile of patients with repeated implantation failure","volume":"14","author":"Yang","year":"2023","journal-title":"Front. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2217261","DOI":"10.1080\/09513590.2023.2217261","article-title":"Recurrent implantation failure versus recurrent implantation success: A preliminary study at proteomic level","volume":"39","author":"Zhao","year":"2023","journal-title":"Gynecol. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"103381","DOI":"10.1016\/j.jprot.2019.103381","article-title":"iTRAQ comparison of proteomic profiles of endometrial receptivity","volume":"203","author":"Bellver","year":"2019","journal-title":"J. Proteom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/humrep\/deg139","article-title":"Analysis of intra-uterine cytokine concentration and matrix-metalloproteinase activity in women with recurrent failed embryo transfer","volume":"18","author":"Inagaki","year":"2003","journal-title":"Hum. Reprod."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yoshii, N., Hamatani, T., Inagaki, N., Hosaka, T., Inoue, O., Yamada, M., Machiya, R., Yoshimura, Y., and Odawara, Y. (2013). Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity. Reprod. Biol. Endocrinol., 11.","DOI":"10.1186\/1477-7827-11-37"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1080\/14789450.2018.1464915","article-title":"Does the dysregulation of matrix metalloproteinases contribute to recurrent implantation failure?","volume":"15","author":"Benkhalifa","year":"2018","journal-title":"Expert. Rev. Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1093\/humrep\/dey274","article-title":"Differential proteomic analysis of endometrial fluid suggests increased inflammation and impaired glucose metabolism in non-implantative IVF cycles and pinpoints PYGB as a putative implantation marker","volume":"33","author":"Azkargorta","year":"2018","journal-title":"Hum. Reprod."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/clinem\/dgz019","article-title":"Uterine Fluid Proteins for Minimally Invasive Assessment of Endometrial Receptivity","volume":"105","author":"Kasvandik","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"841437","DOI":"10.3389\/fphys.2022.841437","article-title":"The Clinical Efficacy of Personalized Embryo Transfer Guided by the Endometrial Receptivity Array\/Analysis on IVF\/ICSI Outcomes: A Systematic Review and Meta-Analysis","volume":"13","author":"Liu","year":"2022","journal-title":"Front. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.fertnstert.2022.07.007","article-title":"Use of the endometrial receptivity array to guide personalized embryo transfer after a failed transfer attempt was associated with a lower cumulative and per transfer live birth rate during donor and autologous cycles","volume":"118","author":"Cozzolino","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1038\/nrm2973","article-title":"Generating and navigating proteome maps using mass spectrometry","volume":"11","author":"Ahrens","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1093\/molehr\/gag037","article-title":"Gene expression profiling of human endometrial receptivity on days LH+2 versus LH+7 by microarray technology","volume":"9","author":"Riesewijk","year":"2003","journal-title":"Mol. Hum. Reprod."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E2744","DOI":"10.1210\/jc.2014-2155","article-title":"Transcriptomic changes during the pre-receptive to receptive transition in human endometrium detected by RNA-Seq","volume":"99","author":"Hu","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","first-page":"177","article-title":"Endometrial Receptivity Analysis\u2014A tool to increase an implantation rate in assisted reproduction","volume":"84","author":"Hromadova","year":"2019","journal-title":"Ces. Gynekol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.fertnstert.2012.09.046","article-title":"The accuracy and reproducibility of the endometrial receptivity array is superior to histology as a diagnostic method for endometrial receptivity","volume":"99","author":"Blesa","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature19949","article-title":"Mass-spectrometric exploration of proteome structure and function","volume":"537","author":"Aebersold","year":"2016","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-6730-8_7","article-title":"Opportunities and Challenges of Multiplex Assays: A Machine Learning Perspective","volume":"1546","author":"Chen","year":"2017","journal-title":"Methods Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/humupd\/dmt048","article-title":"Guidelines for the design, analysis and interpretation of \u2018omics\u2019 data: Focus on human endometrium","volume":"20","author":"Altmae","year":"2014","journal-title":"Hum. Reprod. Update"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:24:56Z","timestamp":1760106296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/7\/2145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,8]]},"references-count":37,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["jcm13072145"],"URL":"https:\/\/doi.org\/10.3390\/jcm13072145","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,8]]}}}