Abstract
Vitamin D, a vital steroid-based hormone in humans, is crucial not only for maintaining calcium and phosphorus balance but also for influencing several biological activities, including cell maturation, programmed cell death, inflammation control, and insulin sensitivity. The presence of vitamin D receptors across both male and female reproductive organs highlights its potential role in reproductive health. Given the widespread global deficiency of vitamin D, this review explores its possible roles in reproductive functions in both sexes and its relationship with outcomes in assisted reproductive technologies (ART). Vitamin D plays roles in critical reproductive mechanisms such as hormone production, sperm development, and the acrosome reaction. Its levels are linked to semen parameters, ovarian function, polycystic ovary syndrome, endometriosis, and more. This review also uncovers conflicting evidence concerning vitamin D levels and ART success rates. Notably, there is a significant gap in robust, randomized controlled trials evaluating the direct benefits of vitamin D supplementation on fertility in humans. Therefore, more research is urgently needed to explore the molecular pathways influenced by vitamin D across various species and populations, alongside well-designed clinical trials.
Key Words: vitamin D, reproductive health, assisted conception, ART
Introduction
Vitamin D is a fat-soluble steroid hormone essential for human health, primarily recognized for its regulatory effects on calcium and phosphorus balance. The two primary forms are vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Both exist in inactive forms, are not interconvertible, and are collectively termed vitamin D (1). Vitamin D3, accounting for approximately 90%–95% of total vitamin D in the body, can be acquired through dietary sources but is predominantly synthesized in the skin from 7-dehydrocholesterol upon exposure to ultraviolet B (UVB) rays from sunlight. Initially, vitamin D is converted in the liver into 25-hydroxyvitamin D [25(OH)D] via the action of vitamin D-25 hydroxylase enzymes (CYP2R1 or CYP27A1). This metabolite binds to vitamin D–binding protein (DBP) and is carried through the bloodstream to the kidneys. There, under the influence of CYP27B1 in proximal convoluted tubules, it is transformed into the active form, 1α,25-dihydroxyvitamin D3 [1,25(OH)₂D₃ or calcitriol], which, bound to DBP, travels to target tissues to perform its biological actions (2, 3). Vitamin D receptors (VDRs) are found in a broad range of organs and tissues, such as the bones, muscles, intestines, kidneys, parathyroid gland, breast, retina, and spleen. Beyond its well-known skeletal functions, vitamin D also participates in various biological mechanisms, including cell growth regulation, programmed cell death, inflammation control, and modulation of insulin resistance. Deficiency in vitamin D has been linked to numerous conditions like rickets, osteoporosis, type 2 diabetes, cardiovascular diseases, cancers, and autoimmune disorders (4, 5). Serum levels of 25(OH)D are considered the most reliable marker for assessing vitamin D status, as it is the primary circulating metabolite of vitamin D. According to the American Endocrine Society’s clinical guidelines (6), vitamin D levels are categorized as deficient when below 20 ng/mL (50 nmol/L), insufficient between 21–29 ng/mL (52.5–72.5 nmol/L), and sufficient when above 30 ng/mL (75 nmol/L). However, the Institute of Medicine (IOM) considers levels exceeding 20 ng/mL (50 nmol/L) to be adequate for health (7). Despite these standards, both deficiency and insufficiency remain widespread globally. Approximately 37% of studies have documented average serum 25(OH)D concentrations below 20 ng/mL, with values across studies ranging from 2.0 to 54.5 ng/mL (8, 9).
