title: The effect of serum vitamin D levels on ovarian reserve markers: a prospective cross-sectional study.
abstract: Is there any association between serum 25-OH vitamin D levels and ovarian reserve markers in infertile women?
  
  
  
  Vitamin D is not associated with the ovarian reserve markers, anti-mullerian hormone (AMH) and antral follicle count (AFC), in infertile women.
  
  
  
  The 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.
  
  
  
  This 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.
  
  
  
  Overall, 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.
  
  
  
  Among 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 log10AMH 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).
  
  
  
  Although 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.
  
  
  
  Although 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.
  
  
  
  No external funding was used for this study. No conflicts of interest are declared.
  
  
  
  N/A.
authors.affiliation: Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Drakopoulos
authors.affiliation: Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
authors.forename: Arne
authors.initials: A
authors.lastname: van de Vijver
authors.affiliation: Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
authors.forename: Valerie
authors.initials: V
authors.lastname: Schutyser
authors.affiliation: Clinic for Gynecology and Obstetrics, Clinical Centre of Vojvodina Novi Sad, Serbia.
authors.forename: Stevan
authors.initials: S
authors.lastname: Milatovic
authors.affiliation: Laboratory of Hormonology and Tumour markers, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Anckaert
authors.affiliation: Laboratory of Hormonology and Tumour markers, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Schiettecatte
authors.affiliation: Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.|Department of Obstetrics and Gynaecology, School of Medicine, University of Zagreb, Croatia.
authors.forename: Christophe
authors.initials: C
authors.lastname: Blockeel
authors.affiliation: Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Camus
authors.affiliation: Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium.
authors.forename: Herman
authors.initials: H
authors.lastname: Tournaye
authors.affiliation: Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium n.polyzos@gmail.com nikolaos.polyzos@uzbrussel.be.|The Fertility Clinic, Skive Regional Hospital, Denmark and Aarhus University, Faculty of Health, Aarhus, Denmark.
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Polyzos
mesh_terms: D054304:Anti-Mullerian Hormone / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002452:Cell Count; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007247:Infertility, Female / Q000097:blood*; D006080:Ovarian Follicle / Q000166:cytology*; D065851:Ovarian Reserve / Q000502:physiology*; D011446:Prospective Studies; D014807:Vitamin D / Q000097:blood*
chemical_list: D015415:Biomarkers; D014807:Vitamin D; D054304:Anti-Mullerian Hormone
keywords: 25-O H vitamin D; AFC; AMH; ovarian reserve; ovarian reserve markers; vitamin D