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Role of Vitamin D
in Infertility
Dr. Indraneel Jadhav
Introduction
1, 25-Dihydroxy vitamin D3
(1,25 - [OH]2 D3) Calcitriol
25- Hydroxy vitamin D3
(25- OH D3)
Cholecalciferol
Inactive and
major
circulating form
Active form
25-Hydroxy vitamin D
1α-hydroxylase
(CYP27B1)
Mechanism of Action:
•Steroid hormone
•Binds to VDR in nucleus to up regulate gene expression in target cells
Sources of Vitamin
80%
20%
Vitamin D2 (Ergocalciferol)-
UV irradiation of ergosterol from yeast and fungi
Vitamin D3
Metabolism Of Vitamin D
In
Reproductive
system
Classical effects - on calcium homeostasis and
bone metabolism
Vitamin D and Steroidgenesis
Vitamin D regulates estrogen biosynthesis through VDR’s
Direct regulation of the expression of the aromatase gene
Maintaining extracellular calcium homoeostasis
Vitamin D increases progesterone secretion by
Granulosa cell leutinisation – HOXA10 expression
Increased 3 β- HSD mRNA levels
 Vitamin D increases placental sex steriod production
 Regulates human chorionic expression
 Secretion from human syncitiotrophoblasts (promoter- CYP19 )
Vitamin D and Follicular Development
Vitamin D allows follicles to reach terminal maturation and ovulation
Inhibiting AMH expression
Potentiates granulosa cell differentiation
Vitamin D maintains luteal phase
Decreases AMHR-II and FSHR gene expression
Potentiates LH hormone
 Vitamin D positively co-related to AMH
 Promoter for the AMH gene contains a vitamin D response element and vit D
upregulates AMH production
Vitamin D and PCOS
Vitamin D supplementation improves menstrual frequency and results in
higher number of dominant follicles
Vitamin D deficiency was independently associated with
Lower insulin sensitivity
Lower HDL-C levels
VDR associated polymorphisms
J Ott, L Wattar , C Kurz. Parameters for calcium metabolism in women
with polycystic ovary syndrome who undergo clomiphene citrate
stimulation: a prospective cohort study. European Journal of
Endocrinology (2012) 166 897–902
Vitamin D and Endometriosis
Endometrium as extra renal site of Vitamin D action
 Expresses 1α Hydroxylase activity through VDR
 Abundance of Vitamin D binding protein in Endometriosis ~3 times
 Vitamin D Helps through immunomodulant action causing
implantation tolerance
 Regulation of cytokine by NK cell
 Attenuates decidual T cell function
 Causes proper implantation
 Up-regulates endometrial transcription factor
Denis et al .The level of serum anti-Müllerian
hormone correlates with vitamin D status in
men and women but not in boys. Rev
Endocrinol2012 May
Vitamin D and In Vitro Fertilisation
Higher levels of Vitamin D in follicular fluid was associated with better IVF
outcomes which also reflected body stores
Vitamin D causes significant increase in sRAGE levels counteracting
advanced glyation end products(AGEs) causing optimal follicular growth
 Vitamin D is an independent predictive factor
for CC stimulation
 Very high Vitamin D levels was associated with poor embryo quality
and lower clinical pregnancy rates
Oskan et al. Replete Vitamin D stores predict reproductive succes following IVF. Fertil &Steril 2010
Vitamin D and Male Reproduction
Androgen Status
Low Vitamin D associated with secondary and compensated hypogonadism
Concordant seasonal variation of testosterone
Semen parameters
Increases progressive sperm motility via VDR-mediated calcium release
Induces acrosome reaction
 Testiculopathy
 Testiculopathic patients showed osteopenia and osteoporosis
Vitamin D Supplementation
Adjunctive agent in therapies
Can be taken orally, relatively safe and cheap vitamin
Endocrine Practice guidelines committee
18 – 70 years- 1500 - 2000 IU daily
Upper limit – 10,000 IU daily
1000 IU/day increases Vitamin D levels 10ng/ml
 Vitamin D intoxication resulting in hyper-calcemia , renal damage and
calcification was not observed until Vitamin D levels > 150 ng/ml
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Role of Vitamin D in Infertility

  • 1. Role of Vitamin D in Infertility Dr. Indraneel Jadhav
  • 2. Introduction 1, 25-Dihydroxy vitamin D3 (1,25 - [OH]2 D3) Calcitriol 25- Hydroxy vitamin D3 (25- OH D3) Cholecalciferol Inactive and major circulating form Active form 25-Hydroxy vitamin D 1α-hydroxylase (CYP27B1) Mechanism of Action: •Steroid hormone •Binds to VDR in nucleus to up regulate gene expression in target cells
  • 3. Sources of Vitamin 80% 20% Vitamin D2 (Ergocalciferol)- UV irradiation of ergosterol from yeast and fungi Vitamin D3
  • 5. In Reproductive system Classical effects - on calcium homeostasis and bone metabolism
  • 6. Vitamin D and Steroidgenesis Vitamin D regulates estrogen biosynthesis through VDR’s Direct regulation of the expression of the aromatase gene Maintaining extracellular calcium homoeostasis Vitamin D increases progesterone secretion by Granulosa cell leutinisation – HOXA10 expression Increased 3 β- HSD mRNA levels  Vitamin D increases placental sex steriod production  Regulates human chorionic expression  Secretion from human syncitiotrophoblasts (promoter- CYP19 )
  • 7. Vitamin D and Follicular Development Vitamin D allows follicles to reach terminal maturation and ovulation Inhibiting AMH expression Potentiates granulosa cell differentiation Vitamin D maintains luteal phase Decreases AMHR-II and FSHR gene expression Potentiates LH hormone  Vitamin D positively co-related to AMH  Promoter for the AMH gene contains a vitamin D response element and vit D upregulates AMH production
  • 8. Vitamin D and PCOS Vitamin D supplementation improves menstrual frequency and results in higher number of dominant follicles Vitamin D deficiency was independently associated with Lower insulin sensitivity Lower HDL-C levels VDR associated polymorphisms J Ott, L Wattar , C Kurz. Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study. European Journal of Endocrinology (2012) 166 897–902
  • 9. Vitamin D and Endometriosis Endometrium as extra renal site of Vitamin D action  Expresses 1α Hydroxylase activity through VDR  Abundance of Vitamin D binding protein in Endometriosis ~3 times  Vitamin D Helps through immunomodulant action causing implantation tolerance  Regulation of cytokine by NK cell  Attenuates decidual T cell function  Causes proper implantation  Up-regulates endometrial transcription factor Denis et al .The level of serum anti-Müllerian hormone correlates with vitamin D status in men and women but not in boys. Rev Endocrinol2012 May
  • 10. Vitamin D and In Vitro Fertilisation Higher levels of Vitamin D in follicular fluid was associated with better IVF outcomes which also reflected body stores Vitamin D causes significant increase in sRAGE levels counteracting advanced glyation end products(AGEs) causing optimal follicular growth  Vitamin D is an independent predictive factor for CC stimulation  Very high Vitamin D levels was associated with poor embryo quality and lower clinical pregnancy rates Oskan et al. Replete Vitamin D stores predict reproductive succes following IVF. Fertil &Steril 2010
  • 11. Vitamin D and Male Reproduction Androgen Status Low Vitamin D associated with secondary and compensated hypogonadism Concordant seasonal variation of testosterone Semen parameters Increases progressive sperm motility via VDR-mediated calcium release Induces acrosome reaction  Testiculopathy  Testiculopathic patients showed osteopenia and osteoporosis
  • 12. Vitamin D Supplementation Adjunctive agent in therapies Can be taken orally, relatively safe and cheap vitamin Endocrine Practice guidelines committee 18 – 70 years- 1500 - 2000 IU daily Upper limit – 10,000 IU daily 1000 IU/day increases Vitamin D levels 10ng/ml  Vitamin D intoxication resulting in hyper-calcemia , renal damage and calcification was not observed until Vitamin D levels > 150 ng/ml

Hinweis der Redaktion

  1. In humans, predominant source of vitamin D : endogenous cutaneous synthesis dietary sources contribute 20% Nutritional forms consist of : D3 (cholecalciferol)- found in fish (i.e. sardine, salmon and mackerel), eggs and calf liver, and D2 (ergocalciferol)- UV irradiation of ergosterol from yeast and fungi (i.e. mushrooms). Both forms are inactive and are efficiently absorbed by gut. Dietary vitamin D is identical to the skin derived form. Recently expression of CYP27B1 in non-renal tissues including placenta and decidua generating Vit D by local mechanisms.
  2. In its active form, vitamin D regulates expression of human chorionic gonadotropin (hCG) in syncytiotrophoblasts and stimulates production of sex steroids.2