{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:55:23Z","timestamp":1789052123244,"version":"build-2803163510"},"reference-count":98,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Recurrent pregnancy loss (RPL) is a multifactorial reproductive disorder with important genetic, endocrine, immune, and metabolic determinants. Growing evidence links vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms to pregnancy complications, including RPL. A narrative review was conducted via a literature search in major databases: PubMed, EMBASE, Scopus, and Web of Science from January 2010 to January 2026, which synthesized observational studies on maternal 25-hydroxyvitamin D [25(OH)D] status and\/or VDR polymorphisms in RPL, with predefined eligibility criteria and qualitative risk-of-bias assessment. Most studies focused on FokI (rs2228570) and the 3\u2032 regulatory block BsmI\/ApaI\/TaqI. FokI is the most extensively studied VDR variant in RPL and showed the most consistent directional association compared with other variants, particularly in Asian and Middle Eastern populations, though the effect varied by study design, ancestry, and covariate adjustment. Contrary to that, investigations of BsmI\/ApaI\/TaqI loci were not consistent due to ancestry-specific linkage disequilibrium (LD). Genotype and vitamin D interaction effects were scarcely studied, with stratified analyses indicating a more significant genotype effect under vitamin D deficiency. From clinical practice perspectives, VDR polymorphisms may explain why some patients with RPL have a poor response to standard vitamin D supplementation. Women with the FokI f allele polymorphism associated with lower VDR activity require higher vitamin D dosing or earlier immunomodulatory support to achieve adequate endometrial receptivity. VDR variation, particularly FokI, may contribute to RPL susceptibility within an endocrine\u2013immune\u2013metabolic framework. Clinical translation will require standardized RPL definitions, concurrent 25(OH)D assessment, robust control for confounders, and analytical models that account for gene\u2013environment interactions.<\/jats:p>","DOI":"10.3390\/biology15110817","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Polymorphisms of Vitamin D Receptor and Immune-Metabolic Mechanisms in Recurrent Pregnancy Loss: Narrative Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2868-4497","authenticated-orcid":false,"given":"Gulzhanat","family":"Aimagambetova","sequence":"first","affiliation":[{"name":"Department of Surgery, School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan"},{"name":"Clinical Academic Department of Women\u2019s Health, CF University Medical Center, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Nemr","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Lebanese American University Medical Center-Rizk Hospital (LAUMCRH), Beirut P.O. Box 11-3288, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7048-1511","authenticated-orcid":false,"given":"Kuralay","family":"Atageldiyeva","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, Nazarbayev University, Astana 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1633-9757","authenticated-orcid":false,"given":"Wassim Y.","family":"Almawi","sequence":"additional","affiliation":[{"name":"Facult\u00e9 des Sciences, Universit\u00e9 de Tunis El Manar, Tunis 2092, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tomkiewicz, J., and Darmochwa\u0142-Kolarz, D. (2023). The diagnostics and treatment of recurrent pregnancy loss. J. Clin. 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