A seasonal distribution in human natural conception and birth rates has been consistently demonstrated, showing a peak conception rate during summer in northern countries with strong seasonal contrast in luminosity [
22]. Experimental studies have demonstrated that the ovary is a target organ for 1,25(OH)
2D
3 raising the possibility that this active metabolite of vitamin D
3 might play a role in modulating ovarian activity [
23]. Experiments investigating the significance for fertility and reproductive capacity, demonstrate that 25(OH)D
3-deficient female rats had reduced fertility rates, decreased litter sizes and compromised mating behavior [
24]. VDR-null mice showed hypergonadotropic hypogonadism with decreased aromatase activities in the ovary, testis and epididymis, uterine hypoplasia, impaired folliculogenesis; decreased sperm counts, decreased sperm motility and histological abnormalities of the testis [
19]. Ablation of 1α-hydroxylase in female mice is accompanied by abnormal ovarian follicle development, uterine hypoplasia and infertility similar to VDR knockout mice [
25,
26]. However, when serum calcium and phosphorus were normalized by a rescue diet in the female 1α-hydroxylase -/- mice, the defective phenotype including dysfunction in the hypothalamic-pituitary-ovarian axis and ovarian angiogenesis were reversed. The authors conclude that the infertility seen in 1,25(OH)
2D
3-deficient mice is an indirect effect mediated by extracellular calcium and phosphorus and not a direct effect of vitamin D deficiency [
27,
28]. Specific human data in this context is sparse. The first study looking at vitamin D and in vitro-fertilization (IVF) success in 10 healthy women undergoing IVF and embryo transfer found an association of raised oestradiol levels during gonadotrophin-induced ovarian stimulation and a significant increase of serum 1,25(OH)
2D
3. (r = 0.787, p < 0.001) [
29,
30]. Ozkan et al. recently showed higher pregnancy and implantation rates across tertiles of 25(OH)D
3 in follicular fluid of 84 infertile women undergoing IVF and proposed follicular fluid 25(OH)D
3 levels as an independent predictor to success of an IVF-cycle [
31] whereas two prospective studies with 101 and 82 women could not confirm these findings [
32,
33]. On the contrary no significant differences in pregnancy rates and embryo quality were found between patients with low (< 50 nmol/l) and moderate (50-75 nmol/) 25(OH)D
3 follicular fluid levels, at high vitamin D levels in follicular fluid (> 75 nmol/l) even a decrease in pregnancy rate and embryo quality was seen [
32,
33]. It was also shown that increased follicular fluid 25(OH)D
3 levels in combination with decreased follicular fluid glucose levels have a negative impact on embryo quality and therefore on IVF outcome [
33]. Moreover, Estes and colleagues found a decreased expression of DBP in the follicular fluid of the IVF success group [
34]. While the results of human studies are contradictory the role of vitamin D on human fertility and reproductive physiology merits further assessment by appropriate longitudinal studies.