Fertility is a function of vitamin D around each egg (follicular fluid) – many studies

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Low vitamin D levels in follicular fluid, but not in serum, are associated with adverse outcomes in assisted reproduction - Feb 2022

Archives of Gynecology and Obstetrics V 305, pages 505–517 https://doi.org/10.1007/s00404-021-06174-9
Kahindo P. Muyayalo, Su Song, Hui Zhai, Hong Liu, Dong-Hui Huang, Hui Zhou, Yang-Jiao Chen & Ai-Hua Liao

Purpose
To assess the relationship between serum/follicular fluid (FF) vitamin D (VD) status and assisted reproductive technology (ART) treatment outcomes among infertile patients.

Methods
A prospective cohort study, including 132 infertile patients scheduled for their first ART treatment cycle, was carried out in a Reproductive Medical Center. Serum and FF samples were collected to assess 25-hydroxy VD [25(OH)D] levels. Low VD level was defined as 25(OH)D concentration of less than 30 ng/mL.

Results
Most infertile patients had low VD levels in serum (88%) and FF (90%). We observed a moderately positive correlation between VD levels in serum and FF (r = 0.34, p < 0.0001). Compared to the group of patients with low VD levels in the FF, those with sufficient VD levels had a significantly higher number of retrieved oocytes (p = 0.03), normal fertilization (p = 0.01), and high-quality embryos (p = 0.001). Moreover, patients with sufficient VD levels in the FF also had significantly higher implantation rates than those with low VD levels (76.92% vs. 46.58%, respectively, p = 0.01) and clinical pregnancy rates (92.31% vs. 61.54%, respectively, p = 0.04).

Conclusion
These data collectively revealed that low VD levels in serum and FF were common among infertile patients. VD levels in FF, but not in serum, were associated with embryo quality, normal fertilization, implantation rates, and clinical pregnancy rates. Further studies are mandatory to determine the molecular mechanism and VD’s potential therapeutic benefits in infertile patients.

References (4 on vit D in follicular fluid)

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48. Paffoni A, Ferrari S, Vigano P, Pagliardini L, Papaleo E, Candiani M et al (2014) Vitamin D deficiency and infertility: insights from in vitro fertilization cycles. J Clin Endocrinol Metab 99(11):E2372–E2376. https://doi.org/10.1210/jc.2014-1802
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The level of vitamin D in follicular fluid and ovarian reserve in an in vitro fertilization program: A pilot study (all levels <25 ng) - May 2022

Science Progress 105(2) https://doi.org/10.1177/00368504221103782
Ji Yeon Han, Sung Woo Kim, Hoon Kim, ...

Background
The level of vitamin D in follicular fluid (FF) according to the ovarian reserve has never been investigated, and the effect of FF vitamin D on the outcome of assisted reproductive technology (ART) remains controversial. The aim of this study is to evaluate the association between FF vitamin D levels and baseline anti-Müllerian hormone (AMH) / ART outcomes.

Methods
Forty-seven patients who underwent controlled ovarian stimulation at the fertility clinic of an academic tertiary care center were enrolled for a prospective observational study. FF was collected from the first aspirated leading follicle of each ovary and assayed by an enzyme-linked immunosorbent assay. Multivariable linear regression analysis was used to assess the association between baseline AMH and FF vitamin D levels with adjustment for basal FSH and serum vitamin D levels.

Results
Both the AMH and serum vitamin D were significant predictors for FF vitamin D. The estimated marginal mean of FF vitamin D level was higher in women with decreased ovarian reserve (DOR) than those with normal ovarian reserve (24.1 ± 2.1 vs. 18.8 ± 1.4 ng/ml, p = 0.048). However, FF vitamin D did not demonstrate any significant associations with cycle outcomes, including fertilization rate and the number and proportion of good embryos at day three.

Conclusion
We observed significantly higher FF vitamin D levels in women with DOR. However, FF vitamin D did not demonstrate any significant associations with the outcome of ART. A larger prospective study is needed to investigate the effect of FF vitamin D on the clinical pregnancy rate and live birth rate.
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FF Vit D levels corrlated with pregnancy test, oocyte count - (did not consider VDR) - July 2022

Follicular fluid 25-hydroxyvitamin D levels determine fertility outcome in patients with polycystic ovary syndrome
Taiwan J Obstet Gynecol. 2022 Jul;61(4):620-625. doi: 10.1016/j.tjog.2022.03.041
Ramazan Ozyurt 1, Cemil Karakus 2

Objective: To determine the possible relationship between follicular fluid 25-hydroxyvitamin D 25(OH)D levels and fertility outcome of women who underwent IVF/ICSI with the diagnosis of lean polycystic ovary syndrome.

Materials and methods: Thirty patients who were diagnosed with PCOS according to the Rotterdam criteria and decided on IVF/ICSI were included in the study. Thirty patients who were scheduled for IVF/ICSI for reasons other than PCOS and matched in terms of age and BMI were taken as the control group (non-PCOS). According to BMI values, patients in both PCOS and non-PCOS groups were lean. Women in both groups were aged 21-35 years with a normal BMI (18.5-24.9 kg/m2) and first IVF/ICSI attempt. Both groups of patients were followed up using the antagonist protocol. Vit D levels were measured in serum and follicular fluid (FF) samples taken on the day of oocyte collection. The correlation between FF vit D levels, the number of total oocytes, MII oocytes and 2 PN zygotes, HOMA-IR, hormonal and demographic parameters, clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate were evaluated.

Results: At the time of oocyte retrieval women with PCOS had similar serum Vitamin D compared to non-PCOS women (21.8 (12.6-24.8) ng/ml vs 22.3 (11.5-25.1) ng/ml, p < 0.54). In FF, assessed on the day of oocyte retrieval, the concentration of Vitamin D was similar in women with PCOS when compared to non-PCOS women (11.2 (9.2-14.4) ng/ml vs 13.3 (11.1-17.4) ng/ml, p < 0.06). For both groups, Vitamin D levels were lower in FF compared to serum vit D. A positive correlation was found between serum and FF Vitamin D concentrations in the full cohort. A positive and significant correlation was found between FF-vit D levels and the number of total oocyte (r = 0.344, p < 0.04) and MII oocyte (r = 0.404, p < 0.02) in the PCOS group. The number of total oocyte, MII oocyte and 2 PN zygotes of the PCOS group were significantly higher than the non-PCOS group. Positive pregnancy test rate, clinical pregnancy and live birth rates were similar in both groups. The miscarriage rates in the non-PCOS group were significantly higher than in the PCOS group.
A positive and significant correlation was also found between FF vit D levels and positive pregnancy test (r = 0.566, p < 0.03) and CPR (r = 0.605, p < 0.02) in PCOS group.
There was no correlation between FF-vit D levels and live birth and miscarriage rates in neither the PCOS nor the non-PCOS group.

Conclusions: Both serum and FF 25-hydroxyvitamin D level of women with PCOS at the time of oocyte retrieval are similar to non-PCOS controls. While FF 25-hydroxyvitamin D levels correlate with total and MII oocyte counts, positive pregnancy test and CPR, it does not correlate with miscarriage and live birth rates.
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Follicular Fluid and follicles

A follicle is a small sac of fluid in the ovaries that contains a developing egg.
One egg per follicle
Women begin puberty with about 300,000 to 400,000 eggs.
Each monthly menstrual cycle a number of follicles, each containing an egg, are selected to grow and mature

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Agreed: Local level of Vitamin D is more important than blood/serum level Vitamin D

At least 5 genes can restrict the level of vitamin D which actually gets to the cell
However, It is both expensive and difficult to measure cell-level of Vitamin D
Many studies have found that high levels of vitamin D (50-70 ng) in the blood greatly increase the cellular Vitamin D
2 groups keep increasing vitamin D dose until the PTH is reduced (Vitamin actually getting to cells
Examples:
Vitamin D is needed for human fertility – goal is 50 ng – Sept 2018
Vitamin D level in eye not associated with level in blood – Jan 2020

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Different Vitamin D levels to stop restrictions due to poor or disease-altered genes

Vitamin D	Treats
150 ng	Multiple Sclerosis *
80 ng	Cluster Headache * Reduced office visits by 4X *
70 ng	Sleep *
60 ng	Breast Cancer death reduced 60% Preeclampsia RCT
50 ng	COVID-19 T1 Diabetes Fertility Psoriasis Infections Review Infection after surgery
40 ng	Breast Cancer 65% lower risk Depression ACL recovery Hypertension Asthma?
30 ng	Rickets

* Evolution of experiments with patients, often also need co-factors

• Click here for more information

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VitaminDWiki - Vitamin D greatly improves Fertility

• Vitamin D is needed for human fertility – goal is 50 ng – Sept 2018
• In-vitro Fertilization costs at least 10,000 dollars, Vitamin D costs 5 dollars
• Women were 50X more likely to be fertile if just 1 ng higher level of vitamin D – Nov 2024
• Infertile patients 1.7X more-likely to become pregnant if take Vitamin D – meta-analysis Feb 2023
• Live birth 1.7 X more likely after IVF if good level of vitamin D – meta-analysis Aug 2020
• If diagnosed infertile, more likely to have live birth if Vitamin D fortification – Feb 2020
• Preconception vitamin D is great - every extra 10 ng associated with 10 percent more likely to have live birth – Aug 2018
• Women with more than minimum vitamin D were 3.4 X more likely to achieve pregnancy and 1.6 X more likely to have live births – June 2017
• Assisted Reproduction – 5 studies concluded vitamin D repletion helps – Review March 2015
• Pregnancy success increased 30 percent if sunny (or vitamin D) one month earlier – June 2015
• IVF 4X more successful for white women with lots of vitamin D – many studies

Increased male Vitamin D increases fertility

• Birth rates doubled with Vitamin D - 300,000 for infertile men – RCT Nov 2017
• Higher vitamin D results in 22% fewer abnormal sperm (Mendelian analysis) – May 2024
• Conception was 3.7X more likely if the male had a good level of Vitamin D – July 2022
• Far better sperm in fertility clinic if more than 30 ng of Vitamin D - June 2022
• Fertility (sperm) associated with vitamin D – meta-analysis Sept 2019
• Infertility - 71 percent of the time of BOTH partners had less than 20 ng of Vitamin D – Aug 2017
• Male fertility 4 X higher if high Vitamin D – Nov 2015
• Vitamin D somewhat assists reproduction – both the mother and the father – May 2014

Decreased Fertility if decreased Vitamin D Receptor

• Unexplained infertility 4X more likely if poor vitamin D receptor – Dec 2020
• Male Infertility is associated with poor Vitamin D Receptor – July 2021

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VitaminDWiki - Genetics chart (Receptor is the most important and easily changed)

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The risk of 44 diseases at least double with poor Vitamin D Receptor

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VitaminDWiki - Vitamin D Receptor activation can be increased in 13+ ways:

Resveratrol,  Omega-3,  Magnesium,  Zinc,   Quercetin,   non-daily Vit D,  Curcumin, intense exercise,   Ginger,   Essential oils, etc   Note: The founder of VitaminDWiki uses 10 of the 13 known VDR activators

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VitaminDWiki - 7 studies in both categories Fertility and Vitamin D Receptor

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