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Reproductive Tissue

Also known as: Vitamin D, Cholecalciferol, Ergocalciferol, Myo-inositol, 1,2,3,4,5,6-cyclohexanehexol, Fertility vitamins, Ovarian support nutrients, Vitamin D and Myo-inositol

Overview

Vitamin D and Myo-inositol are micronutrient supplements used to support reproductive health, particularly in the context of assisted reproductive technology (ART). Vitamin D, available as cholecalciferol (D3) and ergocalciferol (D2), is sourced from fatty fish and supplements. Myo-inositol, a type of sugar alcohol, is found in nuts, seeds, and whole grains. These supplements are investigated for their potential to improve oocyte quality, endometrial receptivity, and embryogenesis. Research on Vitamin D is more mature, with multiple randomized controlled trials (RCTs) and meta-analyses, while Myo-inositol has emerging evidence from RCTs. The evidence quality for Vitamin D is considered moderate, while Myo-inositol requires further replication to confirm its benefits.

Benefits

Vitamin D supplementation is associated with an increased clinical pregnancy rate (OR 1.52, 95% CI 1.08-2.15). However, evidence for live birth rate improvement is currently insufficient. Vitamin D may also improve oocyte quality through the reduction of oxidative stress, although direct evidence is limited. Myo-inositol has shown promise in improving embryo quality, with improved morphology scores (RR 1.34, 95% CI 1.12-1.61), and increased clinical pregnancy rates (RR 1.28, 95% CI 1.08-1.51). It's important to note that many studies on Myo-inositol have focused on populations with polycystic ovary syndrome (PCOS).

How it works

Vitamin D exerts its effects through several mechanisms. It activates the Vitamin D receptor (VDR), which modulates the production of anti-Müllerian hormone (AMH). It also supports endometrial receptivity through calcium homeostasis and reduces inflammatory cytokines in follicular fluid via immunomodulation. Myo-inositol works by sensitizing insulin, which lowers insulin levels in follicular fluid. It also reduces oxidative stress by increasing glutathione peroxidase activity and acts as a second messenger in follicle-stimulating hormone (FSH) signaling, which is crucial for oocyte maturation.

Side effects

Vitamin D supplementation can lead to hypercalciuria (2-3% at doses >4000 IU/day) and, rarely, nephrolithiasis (<0.5%). It can interact with thiazide diuretics and corticosteroids. Myo-inositol can cause gastrointestinal distress (5-10% at doses >4g/day) and, rarely, hypoglycemia in insulin-resistant patients. Caution is advised when using these supplements, especially in individuals with pre-existing medical conditions or those taking medications that may interact with them. It is important to adhere to recommended dosages and consult with a healthcare professional.

Dosage

For Vitamin D, the minimum recommended dosage for general health is 600-800 IU/day. For ART optimization, a dosage of 2000-4000 IU/day is often used, targeting a serum 25(OH)D level above 30 ng/mL. The maximum safe dosage without medical supervision is 4000 IU/day. Vitamin D is best absorbed when taken with food. For Myo-inositol, the minimum dosage is 1000 mg/day, with an optimal range of 2000-4000 mg/day, divided into multiple doses. It is typically taken preconception and throughout ART cycles.

FAQs

Should vitamin D be taken with food?

Yes, vitamin D is a fat-soluble vitamin, and its absorption is improved when taken with meals containing fat.

How long until effects manifest?

Vitamin D requires approximately 8-12 weeks to stabilize serum levels. Myo-inositol may show effects within about 3 menstrual cycles.

Any lab monitoring needed?

For Vitamin D, it is recommended to have 25(OH)D levels tested before starting supplementation and again after 3 months to ensure optimal levels are achieved.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/39127677/ – This study investigates the impact of antioxidants, including Vitamin D, on oocyte quality. It suggests that antioxidants may improve oocyte quality by reducing oxidative stress. However, the role of Vitamin D in this process requires further investigation through human randomized controlled trials.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9896710/ – This meta-analysis of 9 RCTs (n=1,892) found that Vitamin D supplementation increased clinical pregnancy rates (OR 1.52). The study highlights the potential benefits of Vitamin D in improving pregnancy outcomes. However, it also notes the heterogeneity in dosing protocols across the included studies as a limitation.
https://bmjopen.bmj.com/content/13/3/e060483 – This article is a protocol for a systematic review and meta-analysis assessing the effectiveness of vitamin D supplementation on reproductive outcomes in women undergoing assisted reproductive technology (ART). It aims to evaluate the impact of vitamin D on live birth rate, clinical pregnancy rate, and other relevant outcomes. The review will synthesize evidence from randomized controlled trials to provide a comprehensive assessment of vitamin D's role in ART.
https://karger.com/goi/article/doi/10.1159/000540023/911024/Effectiveness-of-Myo-Inositol-on-Oocyte-and-Embryo – This meta-analysis of 12 RCTs (n=1,576) found that Myo-inositol improved embryo quality (RR 1.34). The study suggests that Myo-inositol may enhance embryo development. However, it is important to note that the included studies primarily focused on populations with PCOS, limiting the generalizability of the findings.
https://academic.oup.com/humrep/article/38/3/489/6845502 – This review discusses the role of myo-inositol in improving oocyte quality and subsequent embryo development. It highlights myo-inositol's function as a second messenger in FSH signaling and its potential to enhance oocyte maturation. The review suggests that myo-inositol may be a valuable adjunct in ART, particularly for women with PCOS.