Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome—A Review
Abstract
:1. Introduction
2. Materials and Methods
3. Influence of Vitamin D on Fertility and In Vitro Fertilization
4. Polycystic Ovary Syndrome and Vitamin D Deficiency
5. Vitamin D Deficiency and Pregnancy
6. Vitamin D Deficiency and Female Bone Mineral Density (BMD) in Childbearing Period and Pregnancy-Related Transient Osteoporosis of the Hip
Study | Article Type | Study Group | Summary |
---|---|---|---|
Ó Breasail et al. [92] | Case control study | Healthy pregnant women (n = 53), non-pregnant and non-lactating (n = 37) | Significant decrease in volumetric bone mineral density and a different pattern of microarchitecture were seen mainly in the tibia (not in radius) in the pregnant group, suggesting compartment-specific maternal bone mineral density and microarchitecture changes during pregnancy. |
Moller et al. [91] | Controlled cohort study | Women planning pregnancy (in total 153 women, conceived n = 92), women in postpartum (19 month, n = 31) and age-matched controls (n = 75) | Pregnancy and breastfeeding also lead to reversible bone loss, which returns to pre-pregnancy levels 19 months after delivery, independent of the length of breastfeeding. |
Steib-Furno et al. [99] | Prospective survey and retrospective study | Pregnant women (n = 4900) | Pregnancy-related transient osteoporosis of the hip (PR-TOH) is a rare, benign orthopedic–obstetrical illness, it usually occurs during the third trimester of pregnancy. |
Curtis et al. [93] | Randomized controlled trial | Pregnant women (Placebo group (n = 188), cholecalciferol-supplemented (n = 184)) | The bone resorption marker urinary C-terminal telopeptide of type I collagen (CTX) increased during pregnancy. This occurred to a lesser extent during vitamin D supplementation during pregnancy and this was inversely associated with maternal bone mass following delivery. These results may indicate that vitamin D supplementation may ameliorate and prevent pregnancy-related reversible bone loss in mothers. |
7. Comparability of Vitamin D Studies
8. Summary and Recommendations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Study | Article Type | Study Group | Summary |
Xu et al. [25] | Cell line (animal) | Secondary preantral follicles were isolated from ovaries of rhesus monkeys | Vitamin D increases survival of the preantral follicle, sustains AMH production and enhances the growth of the antral follicle. |
Kinute et al. [21] | Animal Study | VDR null mutant mice (n = 3–10 group) | In females: uterine hypoplasia, decreased aromatase activity and aromatase gene expression were observed; in males: decreased sperm count and decreased motility with histological abnormality of the testis were observed. |
Akhavizadegan et al. [22] | Case control study | Fertile men (n = 116) and infertile men (n = 114) | Men with vitamin D levels below 20 ng/mL have significantly lower sperm counts. The mean vitamin D level in the fertile group was significantly higher than in the infertile group. |
Dennis et al. [19] | Correlative and intervention study | Mature men (n = 113), premenopausal women (n = 35), 5- to 6-yr-old boys (n = 74) | Serum AMH correlates positively with vitamin D levels in men (but not in boys). Vitamin D levels and AMH levels show a seasonal difference in women, with AMH levels falling by 18% in the winter compared to summer. The change in AMH levels correlates with initial AMH levels and the magnitude of the change in vitamin D levels. Vitamin D supplementation prevents seasonal AMH change. |
Ozkan et al. [24] | Prospective Cohort Study | Infertile women undergoing IVF (n = 84) | Vitamin D level influences the outcomes of IVF independently of age, BMI, ethnicity and the number of embryo transfers. Vitamin D levels correlate strongly (r = 0.94) with follicular fluid. |
Study | Article Type | Study Group | Summary |
Tavakoli et al. [48] | Cell line (human) | Endometrial samples (from women with recurrent spontaneous abortion and healthy controls) | Vitamin D supplementation may have a beneficial effect in case of recurrent miscarriages. As a result of vitamin D supplementation, Th2 cytokine dominance was observed with decreased proliferation of inflammatory cytokines. |
Diaz et al. [49] | Cell line (human) | Term placentae samples (37–41 weeks of gestation, from uncomplicated pregnancies) | Calcitriol supplementation prevents the production of TNF alpha, IL-6 and IFN gamma—this is likely mediated by VDR. |
Liu et al. [50] | Cell line (human) | Human trophoblastic cell lines from American Type Tissue Culture Collection | In human trophoblast cells, Vitamin D metabolites significantly enhance antibacterial responses. |
Kuyucu et al. [34] | Animal study | Prepubertal female rats, control group (n = 8), PCOS group (n = 8) and PCOS + D3 group (n = 8) | Vitamin D treatment significantly reduced endometrial, epithelial and stromal thickness in PCOS patients, as well as pathological proliferation and apoptosis. AMH was also decreased as a result of vitamin D supplementation (this however did not reach the level of significance). |
Guo et al. [36] | Case control study | Endometrial samples from women who underwent standardized IVF treatment (n = 16) | VDR plays role in the development of endometrial susceptibility: increased VDR expression in the endometrium (especially in the implantation window of the menstrual cycle) is significantly more likely to lead to pregnancy. |
Zadeh-Vakili et al. [32] | Case control study | PCOS women (n = 260) and women with physiological cycles (n = 221) | The genetic variant of VDR is associated with the severity of the clinical features of PCOS, but not with the risk of the disease itself. |
Aghadavod et al. [38] | Case control study | Control group (n = 20 normal weights and n = 20 over-weights); PCOS group (n = 20 normal weight and n = 20 over-weight) | Vitamin D levels in follicular fluid are significantly lower in PCOS and overweight patients. Vitamin D levels in follicular fluid strongly correlate with BMI. VDR expression in granulosa cells is significantly lower in PCOS/overweight patients than in non PCOS or normal weight individuals. |
Zhao et al. [39] | Case control study | In total, 305 women were divided into 4 groups based on serum vitamin D levels. | Optimal vitamin D levels improve embryo quality and lead to significantly higher clinical pregnancy rates. |
March et al. [27] | Retrospective birth cohort study | In total, 728 women born between 1973–1975 in a single maternity hospital were traced and interviewed in adulthood (age = 27–34 year; n = 728). | Prevalence estimates for Rotterdam and AES may be up two twice of that for NIH criteria A significant proportion of women with PCOS are not diagnosed or are diagnosed late. |
Pal et al. [28] | Retrospective cohort study (Secondary analysis of randomized controlled trial data) | Participants in the Pregnancy in PCOS I randomized controlled trial (n = 540) who met the National Institutes of Health diagnostic criteria for PCOS. | In women with PCOS, serum vitamin D level is an independent predictor of reproductive success rates following induction of ovulation. Probability of ovulation correlates with vitamin D levels in PCOS. The reproductive threshold for serum vitamin D is higher in than that recommended for the non-pregnant population. |
Hahn et al. [45] | Prospective cohort study | PCOS women (n = 120) | In PCOS, insulin resistance correlates negatively with vitamin D levels. |
Pittas et al. [46] | Randomized controlled trial | Caucasian adults (n = 314) | In older healthy adults with impaired fasting glucose (IFG), calcium and vitamin D supplementation may reduce the further development of insulin resistance. |
Study | Article Type | Study Group | Summary |
---|---|---|---|
Wilson et al. [74] | Animal study | VDR+/− virgin female mice (n = 12) + VDR+/− male mice | In VDR−/− placenta, the expression of Deptor and Prr5 involved in mTOR signaling was decreased significantly. |
Cleal et al. [75] | Cell line (human) | Placental samples collected in the Southampton Women’s Survey (n = 102) | Maternal vitamin D and vitamin-D-binding protein levels correlate positively with the expression of amino-acid transporter genes of the placenta. |
Brodowski et al. [77] | Cell line (human) | Cord blood samples from uncomplicated pregnancies and uncomplicated pregnancy villous placentae | Vitamin D promotes the formation of capillary-like tubules and the migration of endothelial colony-forming cells, minimizing the negative effects of preeclampsia. |
Wang et al. [79] | Cell line (human) | Placenta samples from healthy women (38–40 weeks of gestations) | Vitamin D downregulates pro-labor genes such as corticotropin-releasing hormone. This reduces the risk of preterm birth. |
Javorski et al. [78] | Cell line (human) | Pregnant women (n = 189) | Polymorphisms in the VDR gene (Fok-l and Cdx-2) increase the risk of spontaneous preterm birth. |
Wang et al. [80] | Case-control study | GDM women (n = 41) and healthy pregnant women (n = 40) | Placental CYP24A1 protein and mRNA levels responsible for vitamin D catabolism, VDR protein and mRNA levels are increased in GDM. |
Knabl et al. [81] | Case-control study | Placental tissue samples from GDM and control patients (n = 40 GDM and n = 40 controls) | VDR expression is regulated in a bimodal fashion by calcitriol: high doses (0.1 and 1 nmol/mL) lead to downregulation, while low doses (0.01 nmol/mL) lead to VDR upregulation. |
Lacroix et al. [82] | Case-control study | Placental tissue samples from normoglycemic and GDM women. | VDR protein expression was increased in GDM patient placenta samples; Vitamin D decreases IL-6 secretion. |
Hou et al. [61] | Case-control study | Placenta and decidua samples were collected following termination of pregnancy (controls n = 20 and spontaneous miscarriage n = 20) | In cases of spontaneous miscarriage, placental and decidual expression of both the vitamin D receptor and the vitamin-D-binding protein was increased. Women who undergo assisted reproductive technologies should ensure optimal vitamin D levels prior to pregnancy. |
Nguyen et al. [72] | Case-control study | Placentae from pregnancies complicated by idiopathic fetal growth restriction (n = 25) and gestational-matched controls (n = 25) | In cases of idiopathic fetal growth restriction, VDR mRNA and protein levels were all significantly decreased. |
Stougaard et al. [58] | Retrospective cohort study | Woman who gave birth between 1983–1988 (n = 73,237) | There is no association between increased dietary intake of vitamin D and the incidence of preeclampsia. |
Merewood et al. [85] | Retrospective cohort study | Women (n = 253) who had undergone a primary cesarean section (n = 43) | There is a negative association between maternal serum vitamin D levels and cesarean sections. Women with vitamin D levels below 37.5 nmol/L were almost four times more likely to have a cesarean section. |
Lee et al. [51] | Prospective observational study | Women who completed 37 weeks of pregnancy (n = 680) | In total, 71.7% of pregnant women were vitamin D deficient, 21.0% of pregnant women were vitamin D insufficient and 7.3% of pregnant women had adequate vitamin D levels. |
Xu et al. [53] | Prospective cohort study | Pregnant women (n = 827, 101 developed GDM) | Median plasma vitamin D concentrations at the first prenatal visit were significantly lower in women who later developed GMD. |
Andersen et al. [64] | Prospective cohort study | Pregnant women (n = 1683) | The adjusted hazard of first trimester miscarriage is lower at higher vitamin D levels: vitamin D levels below 50 ng/mL double the risk of a miscarriage. No such relationship was found in the second trimester. |
McDonnell et al. [67] | Prospective cohort study | Pregnant women (n = 1064) | Maternal vitamin D levels above 40 ng/mL reduce the risk of preterm birth. |
Raia-Barjat et al. [76] | Prospective multicenter cohort study | Pregnant women (n = 200) | At 32 weeks of gestation, placenta-mediated complications (PMC) were 5-fold higher in vitamin D deficiency patients compared to those with normal vitamin D levels. There is a strong inverse relationship between serum vitamin D levels and the risk of late PMC. Vitamin D plays a role in maintaining placental performance, thus preventing the development of late PMC. |
Wang et al. [84] | Prospective case-control study | Mother-infant dyads (36.8 ± 2.7 weeks of gestational, n = 125) | In total, 56% of newborns were vitamin D deficient. Neonatal vitamin D deficiency may be associated with winter birth, insufficient sunbathing time, high maternal BMI, insufficient egg consumption, insufficient vitamin D supplementation and adverse health insurance status. |
Xiaomang et al. [56] | Randomized controlled trial | Women who had undergone maternity treatment and delivery (n = 450) | Vitamin D supplementation may reduce the incidence of preeclampsia while also lowering the IUGR index. |
Schulz et al. [59] | Randomized controlled trial | Pregnant women (n = 43) | Serum vitamin D levels above 100 ng/mL reduce the expression of soluble Fms-like tyrosine kinase-1 (sFlt-1) and VEGF. Maternal vitamin D supplementation may reduce the transcription of genes that contribute to preeclampsia. |
Jefferson et al. [65] | Randomized controlled trial | Pregnant women (n = 316) | Vitamin D may have a positive impact on the vaginal microbiome: megasphere correlated negatively and L. crispatus correlated positively with plasma vitamin D levels. |
Brooke et al. [87] | Randomized controlled trial | Pregnant women (D-vitamin treated n = 59 and control n = 67) during the last trimester | The risk of SGA in the control group was almost twice that found in the vitamin-D-supplemented group. |
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Várbíró, S.; Takács, I.; Tűű, L.; Nas, K.; Sziva, R.E.; Hetthéssy, J.R.; Török, M. Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome—A Review. Nutrients 2022, 14, 1649. https://doi.org/10.3390/nu14081649
Várbíró S, Takács I, Tűű L, Nas K, Sziva RE, Hetthéssy JR, Török M. Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome—A Review. Nutrients. 2022; 14(8):1649. https://doi.org/10.3390/nu14081649
Chicago/Turabian StyleVárbíró, Szabolcs, István Takács, László Tűű, Katalin Nas, Réka Eszter Sziva, Judit Réka Hetthéssy, and Marianna Török. 2022. "Effects of Vitamin D on Fertility, Pregnancy and Polycystic Ovary Syndrome—A Review" Nutrients 14, no. 8: 1649. https://doi.org/10.3390/nu14081649