Panagiotis Drakopoulos1, Arne van de Vijver1, Valerie Schutyser1, Stevan Milatovic2, Ellen Anckaert3, Johan Schiettecatte3, Christophe Blockeel1,4, Michel Camus1, Herman Tournaye1, Nikolaos P Polyzos5,6. 1. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium. 2. Clinic for Gynecology and Obstetrics, Clinical Centre of Vojvodina Novi Sad, Serbia. 3. Laboratory of Hormonology and Tumour markers, Universitair Ziekenhuis Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium. 4. Department of Obstetrics and Gynaecology, School of Medicine, University of Zagreb, Croatia. 5. Centre for Reproductive Medicine, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels , Belgium n.polyzos@gmail.com nikolaos.polyzos@uzbrussel.be. 6. The Fertility Clinic, Skive Regional Hospital, Denmark and Aarhus University, Faculty of Health, Aarhus, Denmark.
Abstract
STUDY QUESTION: Is there any association between serum 25-OH vitamin D levels and ovarian reserve markers in infertile women? SUMMARY ANSWER: Vitamin D is not associated with the ovarian reserve markers, anti-mullerian hormone (AMH) and antral follicle count (AFC), in infertile women. WHAT IS KNOWN ALREADY: 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. STUDY DESIGN, SIZE, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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 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 CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared. TRIAL REGISTRATION NUMBER: N/A.
STUDY QUESTION: Is there any association between serum 25-OH vitamin D levels and ovarian reserve markers in infertile women? SUMMARY ANSWER: Vitamin D is not associated with the ovarian reserve markers, anti-mullerian hormone (AMH) and antral follicle count (AFC), in infertile women. WHAT IS KNOWN ALREADY: 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 humanovaries, 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, DURATION: 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. PARTICIPANTS/MATERIALS, SETTING, METHODS: 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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 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 CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. No conflicts of interest are declared. TRIAL REGISTRATION NUMBER: N/A.
Authors: Alexandra C Purdue-Smithe; Brian W Whitcomb; JoAnn E Manson; Susan E Hankinson; Lisa M Troy; Bernard A Rosner; Elizabeth R Bertone-Johnson Journal: J Nutr Date: 2018-09-01 Impact factor: 4.798
Authors: Huichu Li; Jaime E Hart; Shruthi Mahalingaiah; Rachel C Nethery; Trang VoPham; Elizabeth Bertone-Johnson; Francine Laden Journal: Environ Res Date: 2021-08-21 Impact factor: 6.498
Authors: Nicola A Dennis; Lisa A Houghton; Michael W Pankhurst; Michelle J Harper; Ian S McLennan Journal: Nutrients Date: 2017-07-08 Impact factor: 5.717
Authors: Soheila Arefi; Gholamreza Khalili; Homa Iranmanesh; Fattaneh Farifteh; Ahmad Hosseini; Human M Fatemi; Barbara Lawrenz Journal: J Ovarian Res Date: 2018-07-24 Impact factor: 4.234