We read with great interest the recent publication by Franasiak et al regarding the impact of vitamin D levels on reproductive outcome of women undergoing in vitro fertilization. As the authors mentioned, it seems that lack of vitamin D is an epidemic and its insufficiency is being associated with an increasing list of chronic conditions, adverse pregnancy outcome, and–lately–compromised fertility results. Opposed to the current trend, authors described in the largest sample analyzed so far of in vitro fertilization patients that vitamin D status was unrelated to pregnancy outcomes. According to their data, as they only transferred high-quality euploid embryos, the impact–if any–might be at the endometrial receptivity level.

It is still not known, as we are in the early stages of research in this area, if vitamin D deficiency may have an impact on the ovary/oocyte, on the embryo, or on the endometrial receptivity. To dissect this question, we have recently analyzed vitamin D levels in women undergoing oocyte donation. This program offers the opportunity to investigate just the endometrial receptivity, as only high-quality embryos obtained from young, healthy oocyte donors are transferred. We analyzed 267 patients, of whom 15.3% were vitamin D replete, 50.2% deficient and 34.4% insufficient. Fertility outcome was not impacted by vitamin D blood levels in oocyte recipients, in line with Franasiak et al. Similarly, receiver operating characteristic curve was not able to detect a cut-off point that may help patients. We even addressed the issue mentioned by Franasiak et al –they may have not been aware due to simultaneous publication times–about measuring not only vitamin D but also its carrier, vitamin D binding protein (VDBP), so we could calculate free circulating vitamin D. Again, no correlation could be found between vitamin D, VDBP, or free vitamin D and reproductive outcome in women undergoing oocyte donation with high-quality embryos.

Many issues are still unsolved. Is vitamin D then affecting oocyte quality, which has not been taken into consideration in the study of Franasiak et al ? If so, suboptimal embryos might be generated in these women and supplementation may have an impact. How relevant is ethnicity here? Should levels be interpreted differently according to the type of assay used? Are there any other molecules apart from 25-hydroxy vitamin D and VDBP that should be evaluated as they may have a more relevant role? The truth is that there are still too many unanswered questions today as to generalize the practice of evaluating or even supplementing vitamin D in patients with the focus on improving their fertility outcome.