Vitamin D Receptor Polymorphism Is Associated With Reduced Follicle Number in Women Utilizing Assisted Reproductive Technologies.

PURPOSE

Calcitriol, or 1,25-hydroxycholecalciferol, is the active form of vitamin D. It binds and activates vitamin D receptor (VDR). Infertility and defective folliculogenesis have been observed in female knockout mice; however, whether polymorphisms affect human ovarian responses to controlled ovarian stimulation (COS) remains unclear. We hypothesized that polymorphisms are associated with infertility and COS responses. Thus, we evaluated the association between the , and polymorphisms and ovarian responses in women undergoing COS.

METHODS

In this study, we recruited a control group ( = 121) comprising volunteers with a history of natural conception and a second group of women undergoing COS ( = 70). , and genotyping was performed restriction fragment length polymorphism analysis or TaqMan qPCR and Sanger sequencing. Intrafollicular 25(OH)D contents were measured in follicular fluid collected from COS patients during oocyte retrieval. Ovarian response parameters were obtained from patient medical records.

RESULTS

There were no significant differences in the genotype frequencies of polymorphisms ( and between the control and COS groups. However, the allele frequency of (C allele) was significantly lower in the COS group than in the control group ( = 0.02). Follicle number but not oocyte number was lower in patients with polymorphic (TC/CC) genotypes ( = 0.03). Importantly, the ratio between the number of follicles retrieved and intrafollicular estradiol concentrations was higher in patients with the TC/CC genotypes ( < 0.02).

CONCLUSION

We identified an association between the polymorphism and reduced follicle number in women undergoing COS, suggesting that signaling affects the ovarian response to stimulation unknown mechanisms.