{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T03:52:10Z","timestamp":1791863530462,"version":"4.3.4"},"reference-count":139,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A limited period of endometrial receptivity is defined by molecular interactions between the embryo and maternal tissues, which are crucial for successful implantation. The results of clinical studies assessing intrauterine human chorionic gonadotropin (hCG) as an endometrial priming agent in in vitro fertilisation (IVF) have been inconsistent, markedly affected by dose, timing, and cycle context. This narrative review summarises molecular data demonstrating that hCG modulates immunological, stromal, endothelial, and epithelial compartments in a coordinated manner, affecting essential endometrial processes. hCG promotes adhesion competence and proliferation in the epithelium via a microRNA-regulated signalling axis (miR-126-3p\u2013PIK3R2\u2013PI3K\/Akt). Intrauterine hCG promotes controlled apposition and invasion at the vascular interface by selectively strengthening endothelial junctional cohesion via VE-cadherin and CD146, without promoting angiogenesis. hCG collaborates with ERK\/mTOR signalling to regulate autophagy and apoptosis, alters steroid\u2013receptor networks in the stroma, initiates early decidual and survival markers (ACTA2, NOTCH1, complement C3), and enhances stress resistance. hCG modifies the immunological milieu by enhancing the activity of regulatory T cells and altering the distribution of uterine natural killer cells. This facilitates immunological tolerance and the remodelling of spiral arteries. These pleiotropic effects together enhance biomarkers and provide a scientific justification for context-dependent clinical responses, including patient-chosen, directed methods for the delivery of intrauterine hCG during IVF.<\/jats:p>","DOI":"10.3390\/ijms27010278","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T05:28:19Z","timestamp":1766986099000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Molecular Crosstalk Between Intrauterine hCG and Endometrial Receptivity: Signalling Pathways, Immune Modulation, and Translational Perspectives in IVF"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9477-7619","authenticated-orcid":false,"given":"Charalampos","family":"Voros","sequence":"first","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios","family":"Chatzinikolaou","sequence":"additional","affiliation":[{"name":"Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Papadimas","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Polykalas","sequence":"additional","affiliation":[{"name":"Athens Medical School, National and Kapodistrian University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aristotelis-Marios","family":"Koulakmanidis","sequence":"additional","affiliation":[{"name":"1st 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University of Athens, 15772 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalampos","family":"Tsimpoukelis","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Anastasia","family":"Daskalaki","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 General Hospital, National and Kapodistrian University of Athens, 80 Vasilissis Sofias Avenue, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-7796","authenticated-orcid":false,"given":"Marianna","family":"Theodora","sequence":"additional","affiliation":[{"name":"1st Department of Obstetrics and Gynecology, \u2018Alexandra\u2019 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