Does Vitamin D Help with Fertility?
Vitamin D
Vitamin D (also called “calciferol”) is a fat-soluble vitamin which is naturally present in few foods and is available to take as a dietary supplement [through D2 (ergocalciferol) and D3 (cholecalciferol)]. It is also produced in the body (endogenously) through the conversion of sunshine on the skin (through ultraviolet (UV) rays), which triggers the Vitamin D synthesis pathway. Vitamin D which is obtained through sun exposure and supplementation is biologically inactive and must undergo several physiologic changes (hydroxylations) to convert Vitamin D to 25-hydroxyvitamin D called 25(OH)D (called calcidiol) in the liver, and then to 1,25-dihydroxyvitamin D called 1,25(OH)2D called calcitriol. This is the active form of Vitamin D in the body. This active form of Vitamin D promotes calcium absorption in the gut, regulates bone remodeling and mineralization, and maintains proper serum levels of calcium and phosphate.
Vitamin D deficiency is very common in most countries. A systematic review has shown that 25(OH)D concentrations below 50 and 25 nmol/L during pregnancy were reported in 64% and 9% of Americans, and 57% and 23% of Europeans, and is highest during the winter months (Pilz). There is data suggesting that low blood levels of Vitamin D may negatively impact fertility, pregnancy outcomes, and lactation (Pilz). This has been shown in several studies, including the following Meta-Analysis of Randomized Controlled Trials (Chu 2018).
Study: Is serum vitamin D associated with live birth rates in women undergoing assisted reproductive therapy (ART)? (Chu 2018)
Methods: Systematic review and meta-analysis of 11 cohort studies including 2700 women, analyzing relationship between Vitamin D levels and assisted reproductive therapy outcomes.
Results: Live birth rate was more likely in women with higher Vitamin D levels compared to those with lower Vitamin D levels (OR 1.33 [1.08-1.65]). Five studies (including 1700 patients) found that women replete in vitamin D were more likely to achieve a positive pregnancy test than women deficient or insufficient in vitamin D (OR 1.34 ([1.04-1.73]). Clinical pregnancy was found to be more likely in women replete in vitamin D (OR 1.46 [1.05-2.02]). There was no association found between miscarriage and vitamin D concentrations (OR 1.12 [0.81-1.54].
Conclusions: Vitamin D deficiency and insufficiency can be an important condition which decreases success rate in women trying to conceive and undergoing ART.
When looking at all available evidence derived from published studies, it appears that Vitamin D supplementation in women trying to conceive is safe, improves Vitamin D and calcium levels in the blood, and protects skeletal health. Randomized controlled trials suggest beneficial effects of Vitamin D supplementation and improved pregnancy and neonatal outcomes, and the serum levels of importance seem to be 25(OH)D of <50 nmol/L or >75 nmol/L.
Note: A meta-analysis documented that early spontaneous pregnancy loss was significantly increased in women with serum 25(OH)D concentrations below 50 nmol/L compared to those with higher 25(OH)D levels (relative risk (RR): 2.24; 95% CI: 1.15 to 4.37. A study in 1191 women with previous pregnancy losses showed that women with serum 25(OH)D concentrations ≥75 nmol/L preconception were more likely to achieve clinical pregnancy (adjusted RR: 1.10; 95% CI: 1.01 to 1.20) and livebirth (RR: 1.15; 95% CI: 1.02 to 1.19) compared to those with lower serum 25(OH)D concentrations.
Our take:
Guidelines suggest a daily Vitamin D intake of 400-2000 IU in order to maintain 25(OH)D concentrations of 50-75nmol/L. We recommend a daily Vitamin D intake of 1000-2000 IU to maintain a serum level in this ideal range. If an intramuscular injection is preferred over daily supplement injection (or a quick catch-up period is desired), then a once monthly injection of 50-100k IU is performed every 4 weeks. This recommendation is based on studies showing that an injection of 100k IU peaks at 4 weeks, and then begins to taper (Gorman 2017). Again, it is best to start these supplements >90 days prior to trying to conceive for them to have optimal effects.