Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review

Fertil Steril. 2014 Aug;102(2):460-468.e3. doi: 10.1016/j.fertnstert.2014.04.046. Epub 2014 Jun 3.


Objective: To report an update on the role of vitamin D (VD) in ovarian physiology with a focus on genes involved in steroidogenesis, follicular development, and ovarian reserve, as well as ovulatory dysfunction associated with polycystic ovary syndrome (PCOS), and ovarian response to assisted reproductive technology (ART).

Design: Systematic review.

Setting: Not applicable.

Patient(s): Human, animal, and cell culture models.

Intervention(s): Pubmed literature search.

Main outcome measure(s): Granulosa cell function, serum antimüllerian hormone (AMH), AMH and its receptor gene expression, soluble receptor for advanced glycation end-products (sRAGE), PCOS parameters, and ART outcome.

Result(s): In human granulosa cells, VD alters AMH signaling, FSH sensitivity, and progesterone production and release, indicating a possible physiologic role for VD in ovarian follicular development and luteinization. In the serum, 25-hydroxyvitamin D (25OH-D) is positively correlated with AMH, and appropriate VD supplementation in VD-depleted women can suppress the seasonal changes that occur in serum AMH. In VD-deficient women with PCOS, VD supplementation lowers the abnormally elevated serum AMH levels, possibly indicating a mechanism by which VD improves folliculogenesis. The antiinflammatory sRAGE serum levels significantly increase in women with PCOS after VD replacement. Although follicular fluid 25OH-D correlates with IVF outcomes, there is a lack of data pertaining to the impact of VD supplementation on pregnancy rates following IVF.

Conclusion(s): This review underscores the need for understanding the mechanistic actions of VD in ovarian physiology and the critical need for randomized trials to elucidate the impact of VD supplementation on controlled ovarian hyperstimulation/IVF outcome and ovulatory dysfunction associated with PCOS.

Keywords: AMH; IVF; PCOS; Vitamin D; folliculogenesis; ovarian reserve; steroidogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Dietary Supplements
  • Female
  • Fertility*
  • Humans
  • Infertility, Female / metabolism*
  • Infertility, Female / physiopathology
  • Infertility, Female / therapy
  • Male
  • Ovarian Follicle / metabolism
  • Ovary / metabolism*
  • Ovary / physiopathology
  • Polycystic Ovary Syndrome / metabolism*
  • Polycystic Ovary Syndrome / physiopathology
  • Polycystic Ovary Syndrome / therapy
  • Pregnancy
  • Reproductive Techniques, Assisted
  • Signal Transduction
  • Treatment Outcome
  • Vitamin D / metabolism*
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / drug therapy
  • Vitamin D Deficiency / metabolism
  • Vitamin D Deficiency / physiopathology


  • Vitamin D