Role of vitamin D in the genesis of recurrent reproductive loss




pregnancy, recurrent miscarriage, early reproductive losses, vitamin D deficiency, 25(ОН)D deficiency, PCR (polymerase chain reaction)


Currently, there is active discussion worldwide regarding the impact of vitamin D deficiency and the manifestations of its immunosuppressive properties on the development of recurrent pregnancy loss. Vitamin D deficiency and insufficiency are quite common, with prevalence ranging from 35% to 80%. Despite modern molecular-genetic technologies, the question of polymorphisms in the vitamin D receptor (VDR) genes remains relevant.

Purpose - analysis of the relationship between VDR genes polymorphisms in women affected by recurrent reproductive loss.

A systematic search of published literature with a meta-analysis was conducted using the PubMed, Web of Science, and Scopus databases for the period from 2021 to 2022. This review examines the association VDR in women with recurrent reproductive losses. There is a connection between low vitamin D levels and the risk of developing various somatic diseases. The review of scientific data confirmed information about the comorbidity of diseases related to vitamin D deficiency or insufficiency. Thus, extragenital pathology creates unfavorable conditions for recurrent pregnancy losses, limits adaptive mechanisms, and contributes to the exacerbation of complications that may arise due to vitamin D deficiency or insufficiency. During the review, it was found that the most prevalent and well-studied polymorphic variants of the VDR gene, such as FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236), and Cdx2, are associated with various diseases, including reproductive losses. In particular, the FokI polymorphism (rs2228570) of the VDR gene acts as an independent factor capable of predicting the level of vitamin D in the blood, influencing pregnancy outcomes.

Conclusions. The obtained data represent significant information for assessing the risk of recurrent reproductive losses and developing new strategies for the prevention and treatment of these conditions.

No conflict of interests was declared by the authors.


Anderson CM, Gillespie SL et al. (2018, Jun). Effects of Maternal Vitamin D Supplementation on the Maternal and Infant Epigenome. Breastfeed Med. 13(5): 371-380.; PMid:29782187 PMCid:PMC6004083

Barbaro G, Inversetti A, Cristodoro M, Ticconi C, Scambia G, Di Simone N. (2023, Jan 29). HLA-G and Recurrent Pregnancy Loss. Int J Mol Sci. 24(3): 2557.; PMid:36768880 PMCid:PMC9917226

Bosdou JK, Konstantinidou E, Anagnostis P. (2019, Jun 27). Vitamin D and Obesity: Two Interacting Players in the Field of Infertility. Nutrients. 11(7): 1455.; PMid:31252555 PMCid:PMC6683323

Deshmukh H, Way SS. (2019, Jan 24). Immunological Basis for Recurrent Fetal Loss and Pregnancy Complications. Annu Rev Pathol. 14: 185-210.; PMid:30183507 PMCid:PMC6566855

Fernando M, Ellery SJ, Marquina C, Lim S, Naderpoor N, Mousa A. (2020, May 20). Vitamin D-Binding Protein in Pregnancy and Reproductive Health. Nutrients. 12(5): 1489.; PMid:32443760 PMCid:PMC7285222

Holick MF et al. (2021). Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96: 1911-1930.; PMid:21646368

Hong Li Y, Marren A. (2018, Jul). Recurrent pregnancy loss: A summary of international evidence-based guidelines and practice. Aust J Gen Pract. 47(7): 432-436.; PMid:30114870

Jenkinson C. (2019). The vitamin D metabolome: an update on analysis and function. Cell Biochem. Funct. 37: 408-423.; PMid:31328813

Ji J, Zhai H, Zhou H, Song S, Mor G, Liao A. (2019, Jun). The role and mechanism of vitamin D-mediated regulation of Treg/Th17 balance in recurrent pregnancy loss. Am J Reprod Immunol. 81(6): e13112.; PMid:30903715

Kilpatrick LE, Boggs ASP, Davis WC et al. (2020, Jan 23). Assessing a method and reference material for quantification of vitamin D binding protein during pregnancy. Clin Mass Spectrom. 16: 11-17.; PMid:34820515 PMCid:PMC8600997

Lima GO, Menezes da Silva AL, Azevedo JEC et al. (2022, Mar 14). 100 years of vitamin D: Supraphysiological doses of vitamin D changes brainwave activity patterns in rats. Endocr Connect. 11(3): e210457.; PMid:35148281 PMCid:PMC8942315

Nielsen OH, Gubatan JM, Juhl CB, Streett SE, Maxwell C. (2022, Jan). Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol. 20(1): 74-87.e3.; PMid:32931960

Pérez-Barrios C, Hernández-Álvarez E, Blanco-Navarro I. (2016). Prevalence of hypercalcemia related to hypervitaminosis D in clinical practice. Clin Nutr. Dec. 35(6): 1354-1358.; PMid:26995293

Poniedziałek-Czajkowska E, Mierzyński R. (2021, Oct 28). Could Vitamin D Be Effective in Prevention of Preeclampsia? Nutrients. 13(11): 3854.; PMid:34836111 PMCid:PMC8621759

Sharif K, Sharif Y, Watad A, Yavne Y, Lichtbroun B, Bragazzi NL et al. (2018, Sep). Vitamin D, autoimmunity and recurrent pregnancy loss: More than an association. Am J Reprod Immunol. 80(3): e12991.; PMid:29923244

Tamblyn JA, Pilarski NSP, Markland AD et al. (2022, Jul). Vitamin D and miscarriage: a systematic review and meta-analysis. Fertil Steril. 18(1): 111-122.; PMid:35637024

Tieland M, Vaes AMM, de Regt MF, Wittwer J. (2018, Jun). Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults. Clin Nutr. 37(3): 808-814.; PMid:28433267

Tiemeyer S, Shreffler K, McQuillan J. (2020, Apr). Pregnancy happiness: implications of prior loss and pregnancy intendedness. J Reprod Infant Psychol. 38(2): 184-198.; PMid:31271303 PMCid:PMC6942239

Várbíró S, Takács I, Tűű L, Nas K. (2022, Apr 15). Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome-A Review. Nutrients. 14(8): 1649.; PMid:35458211 PMCid:PMC9029121

Zejnullahu VA, Zejnullahu VA, Kosumi E. (2021, Oct 16). The role of oxidative stress in patients with recurrent pregnancy loss: a review. Reprod Health. 18(1): 207.; PMid:34656123 PMCid:PMC8520213

Zhao H, Wei X, Yang X. (2021, May). A novel update on vitamin D in recurrent pregnancy loss (Review). Mol Med Rep. 23(5): 382.; PMid:33760145 PMCid:PMC7986007