Table of Contents
Vitamin D deficiency and female infertility: A mechanism review examining the role of vitamin D in ovulatory dysfunction as a symptom of polycystic ovary syndrome
Excerpt
Materials and methods
This review is based on a systematic search strategy with analysis of available literature, evaluating pathophysiological mechanisms and intervention evidence in order to enable evidence-based reasoning for personalised nutrition interventions. This methodology was used to explicitly identify and minimise bias through the systematic approach detailed below, transparent reporting and critical appraisal.
Results
80 eligible papers were accepted for critical appraisal, comprising 18 review papers (23%), 34 mechanistic, in vitro (Table S1.1) and animal (Table S1.2) studies (43%) (Table 2) and 28 human intervention (Table S1.4) papers (35%) (Table 3).
Analysis and evaluation of studies identified three key themes potentially linking vitamin D deficiency with the pathophysiology of female infertility in PCOS, specifically focused on abnormal folliculogenesis (Section 3.1.2), hormone regulation (Section 3.1.3
Mechanistic evidence
The examined literature highlighted an association between PCOS and vitamin D deficiency, with hormonal imbalances observed. An accumulation of pro-inflammatory AGEs was linked to disrupted follicular development culminating in diminished rates of ovulation. In addition, animal and in vitro studies demonstrated the potential multi-faceted contribution of vitamin D in creating a suitable reproductive environment. However, despite promising evidence for a potential role of vitamin D in
Conclusion
The reportedly widespread prevalence of vitamin D deficiency and frequent occurrence in women with PCOS, make supplementation a seemingly encouraging intervention for ameliorating symptoms of ovulatory dysfunction in PCOS. This mechanism review hypothesised that vitamin D deficiency is associated with female infertility through impaired ovulatory function as a result of dysregulated follicle development, hormone levels and elevated oxidative stress. Despite some mechanistic evidence in favour
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgements
Thank you to Marina Mastrostefano for valuable input, support and guidance.
Declaration of competing interest
The authors declare no conflict of interest.
Abstract
Around one billion people worldwide are understood to have sub-optimal levels of vitamin D. Polycystic ovary syndrome (PCOS) is reportedly a primary reason for female infertility. The main objective of this research was to understand the mechanistic role of vitamin D in the pathogenesis of female infertility in PCOS, specifically in relation to ovarian follicle development. In addition, the impact of vitamin D deficiency on oxidative stress and hormone production central to folliculogenesis was explored. The efficacy of vitamin D supplementation as an intervention to ameliorate ovulatory dysfunction in individuals with PCOS was evaluated. The systematic search strategy included three stages of search with a critical appraisal of the accepted papers: 1) other review papers; 2) primary mechanistic animal, in vitro and human studies; 3) primary intervention studies. In total, 80 papers were examined in detail and results analysed and evaluated. Mechanistic evidence indicated an association between vitamin D deficiency and impaired ovulatory function. Sub-optimal vitamin D levels were implicated in disrupted reproductive hormone balance, including overproduction of anti-mullerian hormone (AMH); accumulation of pro-inflammatory Advanced Glycation End Products (AGEs) and formation of Reactive Oxygen Species (ROS) in ovarian tissue, leading to abnormal folliculogenesis. Human intervention studies demonstrated the capability of vitamin D supplementation for restoring sufficient serum calcidiol (25(OH)D) levels in deficient individuals. Furthermore, the anti-inflammatory benefit of vitamin D was illustrated in studies examining the impact on oxidative stress. Co-supplementation with calcium was shown to benefit follicle growth; oxidative stress reduced with calcium, omega-3 fatty acid or probiotic co-supplementation.