• Panagiotis Drakopoulos, Arne van de Vijver, Valerie Schutyser, Stevan Milatovic, Ellen Anckaert, Johan Schiettecatte, Christophe Blockeel, Michel Camus, Herman Tournaye, and Nikolaos P Polyzos.
• Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
• Hum. Reprod. 2017 Jan 1; 32 (1): 208-214.

Study QuestionIs there any association between serum 25-OH vitamin D levels and ovarian reserve markers in infertile women?Summary AnswerVitamin D is not associated with the ovarian reserve markers, anti-mullerian hormone (AMH) and antral follicle count (AFC), in infertile women.What Is Known AlreadyThe mechanism underlying the relationship between vitamin D deficiency and reproduction is still unclear; however, evidence indicates a potential direct negative impact on ovarian function. This is mainly due to the fact that gonadal function may be altered by vitamin D deficiency, as observed by the expression of vitamin D receptor mRNA in human ovaries, mixed ovarian cell cultures and granulosa cell cultures. On the other hand, results from clinical studies are conflicting, with some suggesting that vitamin D status is associated with ovarian reserve, whereas other cross-sectional studies have not found any significant correlation between vitamin D and AMH levels.Study Design, Size, DurationThis study was a prospective cross-sectional study from the Centre for Reproductive Medicine at the University Hospital of Brussels. The duration of the study was one year.Participants/Materials, Setting, MethodsOverall, the study included 283 consecutive infertile women younger than 42 years old and undergoing their first treatment cycle in our institution. All patients were recruited within a time interval of 12 months from the initiation of the study, before undergoing infertility treatment. Women consuming vitamin D supplements or taking medication for systematic disease or women who had undergone ovarian surgery were excluded from the study. All infertile women had serum AMH and vitamin D sampled on the same day. AFC was measured on the second or third day of the first cycle following the blood sampling for the determination of AMH and 25-OH vitamin D levels.Main Results And The Role Of ChanceAmong all patients, 30.7% (n = 87) were vitamin D deficient (<20 ng/mL) whereas 69.3% (n = 196) had normal vitamin D levels (≥20 ng/mL). The mean AMH and AFC levels did not differ significantly between the two groups: AMH 3.9 μ/L (±3.8) versus 4.3 μ/L (±4.8), (P value = 0.5) and AFC 13.9 (±13.3) versus 12.7 (±11.4), (P = 0.7), respectively. No correlation was observed between 25-O H vitamin D and AMH (spearman's r = 0.02, P value = 0.7) or AFC (spearman's r = -0.02, P value = 0.7). In multiple linear regression analysis, after adjusting for potential confounders (age, BMI, smoking status, infertility cause and season of blood sampling), the regression slope in all participants for total 25OH-D predicting log10 AMH was 0.006 [standard error (SE) = 0.07, P value = 0.9]. Similarly, no significant association was observed between AFC and vitamin D levels, even after controlling for relevant co-variants (regression coefficient -0.09. SE 0.08, P value = 0.2).Limitations, Reasons For CautionAlthough this is the first prospective study to evaluate the relationship between vitamin D and the most important ovarian reserve markers (AMH and AFC), we need to acknowledge that the data used to generate the study findings are cross-sectional in nature. In this regard, we cannot generate or exclude any causal effect hypothesis. Nevertheless, our data support that an association between vitamin D and ovarian reserve markers is highly unlikely to exist.Wider Implications Of The FindingsAlthough data from basic research indicate that vitamin D deficiency may have an effect on steroidogenesis and follicular development, our study, by prospectively recruiting a large number of infertile women, clearly demonstrates that vitamin D deficiency is highly unlikely to have a detrimental effect on ovarian reserve. Ongoing prospective and translational research projects are currently being conducted in order to evaluate the potential effect of vitamin D deficiency on reproductive outcome mediated through either an effect on the oocyte quality or on endometrial receptivity and embryo implantation.Study Funding/Competing InterestsNo external funding was used for this study. No conflicts of interest are declared.Trial Registration NumberN/A.© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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