Oral Vitamin D Supplementation does not Impact Cytokine Levels in Uterine Fluid of Women Undergoing Assisted Reproduction Technology (ART)

Abstract Background: Cytokines and chemokines, secreted in the intrauterine environment, are fundamental for the molecular crosstalk between endometrium and preimplantation embryo. Whether Vitamin D can have a beneficial effect on endometrial district and immune cells is still unclear. To fill this gap, the aim of this study was to explore if Vitamin D supplementation can act on intrauterine milieu as immuno-modulator. Methods: We present a report of a secondary outcome from the SUNDRO clinical trial, a multi-center randomized double-blinded trial aimed to explore the effects of Vitamin D replacement (a single dose of 600,000 IU of 25-hydroxy Vitamin D or placebo) in insufficient women undergoing autologous ART cycles. Inclusion criteria were female age between 18-39 years, with body mass index between 18 and 25 Kg/m2. Uterine fluid samples were collected during the secretory phase of the menstrual cycle that proceeded the oocyte retrieval. The quantitative determination of twenty-seven cytokines in endometrial secretion samples was performed by using a multiplex immunoassay.Results: Forty-nine uterine fluid samples (UF) were collected during the secretory phase of the menstrual cycle prior to oocyte retrieval. Our data revealed no differences in UF composition of Vitamin D supplemented women (n=17) compared with the placebo group (n=32), also when protein normalization was performed. In addition, no significant differences were found in mediators relative content of UFs from women who conceived (n=19) compared with the non-pregnant group (n=30). Conclusions: The explored in vivo vitamin D replacement regimen is unlikely to directly influence the cytokine and chemokine endometrial milieu. EudraCT registration number: 2015-004233-27.