AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025370398
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ORIGINAL RESEARCH ARTICLE

Correlation between follicular fluid 25-hydroxyvitamin D levels and IVF embryo quality in women with diminished ovarian reserve: A metabolomic study

Aiping Zhang1,2,3 ,  Yuzi Li1 ,  Liang Zhao1 ,  Ailin Lan1 ,  Feifei Xu2 ,  Qianqian Hong4 ,  Xuehong Zhang1,2,3*
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1 The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China
2 The Assisted Reproductive Medicine Center of The First Hospital of Lanzhou University, Lanzhou, Gansu, China
3 Key Laboratory for Reproductive Medicine and Embryo, Gansu Provincial Department of Science and Technology, Lanzhou, Gansu, China
4 Department of Clinical Medicine, First Clinical Medical College, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, China
EJMO, 025370398 https://doi.org/10.36922/EJMO025370398
Received: 14 September 2025 | Revised: 18 December 2025 | Accepted: 18 December 2025 | Published online: 18 March 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Improving pregnancy outcomes for women with diminished ovarian reserve (DOR) is a key area of focus in assisted reproductive technology (ART).

Objective: This study aims to investigate the association between 25-hydroxyvitamin D (25-[OH]D) levels in follicular fluid (FF) of women with diminished ovarian reserve (DOR) and embryo quality during in vitro fertilization (IVF), and to perform a metabolomics analysis.

Methods: A total of 54 women with DOR and 62 women with normal ovarian reserve (control) were enrolled. Based on FF 25-(OH)D levels, both DOR and control cases were stratified into two subgroups: the vitamin D non-deficient (VDH) and vitamin D deficient (VDL). Baseline characteristics and IVF laboratory outcomes were compared among groups and subgroups. Untargeted metabolomic profiling of FF was then performed to identify differences between subgroups.

Results: FF vitamin D levels were significantly lower in the DOR group than in controls. In both cohorts, the normal fertilization rate was significantly higher in the VDH subgroup than in the VDL subgroup. Metabolites significantly upregulated in the VDH subgroup included phospholipids, hydroxychloroquine, and serinyltryptophan. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed significant enrichment in glycerophospholipid metabolism in the VDH subgroup. In the DOR group, the DOR-VDH subgroup exhibited upregulation of steroid hormone biosynthesis and vitamin metabolism pathways, particularly those mediated by cytochrome P450, relative to the DOR-VDL subgroup.

Conclusion: Vitamin D may enhance the follicular microenvironment in DOR patients primarily by regulating lipid metabolism, thereby improving oocyte and embryo quality and developmental potential.

Keywords
Vitamin D
Diminished ovarian reserve
In vitro fertilization
Follicular fluid
Lipid metabolism
Funding
This work was supported by the Natural Science Foundation of Gansu Province (20JR10RA675) and the Hospital Foundation Project of the First Hospital of Lanzhou University (ldyyyn2020-12).
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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