Follicular fluid concentrations of the vitamin D metabolite 24,25(OH)2D3 are positively associated with live birth rate after assisted reproductive technology

OBJECTIVE: To investigate the relationship between concentrations of vitamin D metabolites in follicular fluid and outcome of assisted reproductive technology (ART) treatment.

DESIGN: Prospective cohort study including 116 women undergoing in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) treatment.

RESULTS: All measured vitamin D metabolites 25OHD3, 1,25(OH)2D3 and 24,25(OH)2D3 are detectable in follicular fluid. Follicular fluid concentration of the 24,25(OH)2D3 metabolite was higher than corresponding serum values, while the opposite phenomenon was observed for the 1,25(OH)2D3 metabolite. Local conversion is plausible as the vitamin D activating enzymes (CYP2R1 and CYP27B1) as well as the vitamin D receptor (VDR) are highly expressed in the developing follicle. Women who achieved a live birth had 29 % higher 24,25(OH)2D3 and 15 % higher 25OHD3 concentrations in their follicular fluid (18 ± 7.9 versus 14 ± 6.2 nmol/L, p = 0.008 and 71 ± 22 versus 62 ± 18 nmol/L, p = 0.025, respectively) compared to women not achieving a live birth. Moreover, women with a low (≤ 15 %) follicular fluid 1,25(OH)2D3/24,25(OH)2D3 ratio had a higher live birth rate compared to women with a medium (16-84 %) or high (≥ 85 %) ratio (live birth rate: 53 % vs 29 % and 12 %, respectively, p = 0.032).

CONCLUSION: This study reveals that high levels of 24,25(OH)2D3 and low levels of the 1,25(OH)2D3/24,25(OH)2D3 ratio in follicular fluid are associated with increased live birth rates in women undergoing IVF/ICSI treatment. Conversion of vitamin D metabolites systemically or in the ovarian follicle may affect ART outcome. Further studies are warranted to support the findings from this pilot study and identify regulators of ovarian vitamin D metabolites.