RESEARCH PAPER
The role of vitamin D in reproductive dysfunction in women – a systematic review
Krzysztof Łukaszuk
1,2,9
1
Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdansk, Poland
2
INVICTA Fertility and Reproductive Center, Gdańsk, Poland
3
Centre for Reproductive Medicine KRIOBANK, Białystok, Poland
4
Medical University of Bialystok, Poland
5
Department of Chemical and Process Engineering Chemical Faculty, Gdansk University of Technology, Poland
6
INVICTA Fertility and Reproductive Center, Warszawa, Poland
7
First Department of Obstetrics and Gynaecology, Medical Center of Postgraduate Education, Warsaw, Poland
8
Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences, Department of Reproductive Immunology and Pathology, Olsztyn, Poland
9
Department of Gyneacological Endocrinology, Medical University of Warsaw, Warsaw, Poland
Corresponding author
Patrycja Skowrońska
Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdansk, Poland
Department of Obstetrics and Gynecological Nursing, Faculty of Health Sciences, Medical University of Gdansk, Poland
Ann Agric Environ Med. 2016;23(4):671–676
KEYWORDS
ABSTRACT
Vitamin D is essential for the proper functioning of the human body. There is also evidence of its strong association with fertility problems in women. This review aims to evaluate the relationship between vitamin D and diseases affecting women’s fertility (polycystic ovarian syndrome (PCOS), uterine leiomyomas and endometriosis), and in vitro fertilization (IVF) outcome. A systematic review of the literature was conducted in Scopus and PubMed for relevant English language publications since 1989. Vitamin D influences the functioning of the reproductive system in women and has been associated with PCOS, uterine leiomyomas, endometriosis and in vitro fertilization (IVF) outcome. However, further studies on larger groups of patients are needed to establish what role vitamin D plays in the treatment of female infertility.
REFERENCES (78)
2.
Webb AR. Who, what, where and when-influences on cutaneous vitamin D synthesis. Prog Biophys Mol Biol. 2006; 92(1): 17–25.
3.
Anagnostis P, Karras S, Goulis DG. Vitamin D in human reproduction: a narrative review. Int J Clin Pract. 2013; 67(3): 225–35.
4.
Prosser DE, Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem Sci. 2004; 29(12): 664–73.
5.
Prevention and management of osteoporosis. World Health Organ Tech Rep Ser. 2003; 921: 1–164, back cover.
6.
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(7): 1911–30.
7.
Bikle D. Vitamin D: Production, Metabolism, and Mechanisms of Action. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000 [cited 2016 Jul 23]. Available from: http://www.ncbi.nlm.nih.gov/bo....
8.
Haussler MR, Jurutka PW, Mizwicki M, Norman AW. Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)₂vitamin D₃: genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab. 2011; 25(4): 543–59.
9.
Gombart AF. The vitamin D–antimicrobial peptide pathway and its role in protection against infection. Future Microbiology. 2009; 4(9): 1151–65.
10.
Wang T-T, Nestel FP, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004; 173(5): 2909–12.
11.
Nagpal S, Na S, Rathnachalam R. Noncalcemic actions of vitamin D receptor ligands. Endocr Rev. 2005; 26(5): 662–87.
12.
Bręborowicz G. Położnictwo i ginekologia. Warszawa: Wydawnictwo Lekarskie PZWL; 2005 (in Polish).
13.
Sayegh L, Fuleihan GE-H, Nassar AH. Vitamin D in endometriosis: a causative or confounding factor? Metab Clin Exp. 2014; 63(1): 32–41.
14.
Agic A, Xu H, Altgassen C, Noack F, Wolfler MM, Diedrich K, et al. Relative expression of 1,25-dihydroxyvitamin D3 receptor, vitamin D 1 alpha-hydroxylase, vitamin D 24-hydroxylase, and vitamin D 25-hydroxylase in endometriosis and gynecologic cancers. Reprod Sci. 2007; 14(5): 486–97.
15.
Vilarino FL, Bianco B, Lerner TG, Teles JS, Mafra FA, Christofolini DM, et al. Analysis of vitamin D receptor gene polymorphisms in women with and without endometriosis. Hum Immunol. 2011; 72(4): 359–63.
16.
Somigliana E, Panina-Bordignon P, Murone S, Di Lucia P, Vercellini P, Vigano P. Vitamin D reserve is higher in women with endometriosis. Hum Reprod. 2007; 22(8): 2273–8.
17.
Miyashita M, Koga K, Izumi G, Sue F, Makabe T, Taguchi A, et al. Effects of 1,25-Dihydroxy Vitamin D 3 on Endometriosis. The Journal of Clinical Endocrinology & Metabolism. 2016; 101(6): 2371–9.
18.
Hartwell D, Rødbro P, Jensen SB, Thomsen K, Christiansen C. Vitamin D metabolites--relation to age, menopause and endometriosis. Scand J Clin Lab Invest. 1990; 50(2): 115–21.
19.
Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA. Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am J Epidemiol. 2013; 177(5): 420–30.
20.
Borkowski J, Gmyrek GB, Madej JP, Nowacki W, Goluda M, Gabryś M, et al. Serum and peritoneal evaluation of vitamin D-binding protein in women with endometriosis. Postepy Hig Med Dosw (Online). 2008; 62: 103–9.
21.
Faserl K, Golderer G, Kremser L, Lindner H, Sarg B, Wildt L, et al. Polymorphism in vitamin D-binding protein as a genetic risk factor in the pathogenesis of endometriosis. J Clin Endocrinol Metab. 2011; 96(1): E233–241.
22.
Practice Committee of the American Society for Reproductive Medicine. Endometriosis and infertility: a committee opinion. Fertil Steril. 2012; 98(3): 591–8.
23.
Lessey BA, Castelbaum AJ, Sawin SW, Buck CA, Schinnar R, Bilker W, et al. Aberrant integrin expression in the endometrium of women with endometriosis. J Clin Endocrinol Metab. 1994; 79(2): 643–9.
24.
Wei Q, St Clair JB, Fu T, Stratton P, Nieman LK. Reduced expression of biomarkers associated with the implantation window in women with endometriosis. Fertil Steril. 2009; 91(5): 1686–91.
25.
Taylor HS, Bagot C, Kardana A, Olive D, Arici A. HOX gene expression is altered in the endometrium of women with endometriosis. Hum Reprod. 1999; 14(5): 1328–31.
26.
D’Ambrosio D, Cippitelli M, Cocciolo MG, Mazzeo D, Di Lucia P, Lang R, et al. Inhibition of IL-12 production by 1,25-dihydroxyvitamin D3. Involvement of NF-kappaB downregulation in transcriptional repression of the p40 gene. Journal of Clinical Investigation. 1998; 101(1): 252–62.
27.
Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999; 84(11): 4006–11.
28.
Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997; 18(6): 774–800.
29.
Mitri J, Dawson-Hughes B, Hu FB, Pittas AG. Effects of vitamin D and calcium supplementation on pancreatic cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial. American Journal of Clinical Nutrition. 2011; 94(2): 486–94.
30.
George PS, Pearson ER, Witham MD. Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta-analysis. Diabet Med. 2012; 29(8): e142–150.
31.
Wehr E, Pilz S, Schweighofer N, Giuliani A, Kopera D, Pieber TR, et al. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol. 2009; 161(4): 575–82.
32.
Li HWR, Brereton RE, Anderson RA, Wallace AM, Ho CKM. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metab Clin Exp. 2011; 60(10): 1475–81.
33.
Ngo DTM, Chan WP, Rajendran S, Heresztyn T, Amarasekera A, Sverdlov AL, et al. Determinants of insulin responsiveness in young women: Impact of polycystic ovarian syndrome, nitric oxide, and vitamin D. Nitric Oxide. 2011; 25(3): 326–30.
34.
Pittas AG, Lau J, Hu FB, Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007; 92(6): 2017–29.
35.
Milner RD, Hales CN. The role of calcium and magnesium in insulin secretion from rabbit pancreas studied in vitro. Diabetologia. 1967; 3(1): 47–9.
36.
Lerchbaum E, Obermayer-Pietsch B. MECHANISMS IN ENDO-CRINOLOGY: Vitamin D and fertility: a systematic review. European Journal of Endocrinology. 2012; 166(5): 765–78.
37.
Maestro B, Molero S, Bajo S, Dávila N, Calle C. Transcriptional activation of the human insulin receptor gene by 1,25-dihydroxyvitamin D(3). Cell Biochem Funct. 2002; 20(3): 227–32.
38.
Shoelson SE, Herrero L, Naaz A. Obesity, inflammation, and insulin resistance. Gastroenterology. 2007; 132(6): 2169–80.
39.
Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, et al. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2006; 114(10): 577–83.
40.
Mahmoudi T, Gourabi H, Ashrafi M, Yazdi RS, Ezabadi Z. Calciotropic hormones, insulin resistance, and the polycystic ovary syndrome. Fertil Steril. 2010; 93(4): 1208–14.
41.
Panidis D, Balaris C, Farmakiotis D, Rousso D, Kourtis A, Balaris V, et al. Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome. Clin Chem. 2005; 51(9): 1691–7.
42.
Pal L, Berry A, Coraluzzi L, Kustan E, Danton C, Shaw J, et al. Therapeutic implications of vitamin D and calcium in overweight women with polycystic ovary syndrome. Gynecological Endocrinology. 2012; 28(12): 965–8.
43.
Kamycheva E, Joakimsen RM, Jorde R. Intakes of calcium and vitamin d predict body mass index in the population of Northern Norway. J Nutr. 2003; 133(1): 102–6.
44.
Merino PM, Codner E, Cassorla F. A rational approach to the diagnosis of polycystic ovarian syndrome during adolescence. Arquivos Brasileiros de Endocrinologia & Metabologia. 2011; 55(8): 590–8.
45.
Yildizhan R, Kurdoglu M, Adali E, Kolusari A, Yildizhan B, Sahin HG, et al. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet. 2009; 280(4): 559–63.
46.
Shahrokhi SZ, Ghaffari F, Kazerouni F. Role of vitamin D in female Reproduction. Clinica Chimica Acta. 2016; 455: 33–8.
47.
Kotsa K, Yavropoulou MP, Anastasiou O, Yovos JG. Role of vitamin D treatment in glucose metabolism in polycystic ovary syndrome. Fertil Steril. 2009; 92(3): 1053–8.
48.
Irani M, Minkoff H, Seifer DB, Merhi Z. Vitamin D increases serum levels of the soluble receptor for advanced glycation end products in women with PCOS. J Clin Endocrinol Metab. 2014; 99(5): E886–890.
49.
Ciavattini A, Di Giuseppe J, Stortoni P, Montik N, Giannubilo SR, Litta P, et al. Uterine fibroids: pathogenesis and interactions with endometrium and endomyometrial junction. Obstet Gynecol Int. 2013; 2013: 173184.
50.
Laughlin SK, Schroeder JC, Baird DD. New directions in the epidemiology of uterine fibroids. Semin Reprod Med. 2010; 28(3): 204–17.
51.
Sharan C, Halder SK, Thota C, Jaleel T, Nair S, Al-Hendy A. Vitamin D inhibits proliferation of human uterine leiomyoma cells via catechol-O-methyltransferase. Fertil Steril. 2011; 95(1): 247–53.
52.
Bläuer M, Rovio PH, Ylikomi T, Heinonen PK. Vitamin D inhibits myometrial and leiomyoma cell proliferation in vitro. Fertility and Sterility. 2009; 91(5): 1919–25.
53.
Halder SK, Sharan C, Al-Hendy A. Vitamin D treatment induces dramatic shrinkage of uterine leiomyomas growth in the Eker rat model. Fertility and Sterility. 2010; 94(4): S75–S76.
54.
Abdelraheem MS, Al-Hendy A. Serum vitamin D3 level inversely correlates with total fibroid tumor burden in women with symptomatic uterine fibroid. Fertility and Sterility. 2010; 94(4): S74.
55.
Paffoni A, Somigliana E, Vigano’ P, Benaglia L, Cardellicchio L, Pagliardini L, et al. Vitamin D Status in Women With Uterine Leiomyomas. The Journal of Clinical Endocrinology & Metabolism. 2013; 98(8): E1374–E1378.
56.
Marshall LM, Spiegelman D, Barbieri RL, Goldman MB, Manson JE, Colditz GA, et al. Variation in the incidence of uterine leiomyoma among premenopausal women by age and race. Obstet Gynecol. 1997; 90(6): 967–73.
57.
Kjerulff KH, Langenberg P, Seidman JD, Stolley PD, Guzinski GM. Uterine leiomyomas. Racial differences in severity, symptoms and age at diagnosis. J Reprod Med. 1996; 41(7): 483–90.
58.
Rostand SG. Vitamin D, blood pressure, and African Americans: toward a unifying hypothesis. Clin J Am Soc Nephrol. 2010; 5(9): 1697–703.
59.
Baird DD, Hill MC, Schectman JM, Hollis BW. Vitamin d and the risk of uterine fibroids. Epidemiology. 2013; 24(3): 447–53.
60.
Sabry M, Halder SK, Allah ASA, Roshdy E, Rajaratnam V, Al-Hendy A. Serum vitamin D3 level inversely correlates with uterine fibroid volume in different ethnic groups: a cross-sectional observational study. Int J Womens Health. 2013; 5: 93–100.
61.
Sabry M, Al-Hendy A. Medical treatment of uterine leiomyoma. Reprod Sci. 2012; 19(4): 339–53.
62.
Mitro SD, Zota AR. Vitamin D and uterine leiomyoma among a sample of US women: Findings from NHANES, 2001–2006. Reproductive Toxicology. 2015; 57: 81–6.
63.
Walker CL, Stewart EA. Uterine fibroids: the elephant in the room. Science. 2005; 308(5728): 1589–92.
64.
Stewart EA, Friedman AJ, Peck K, Nowak RA. Relative overexpression of collagen type I and collagen type III messenger ribonucleic acids by uterine leiomyomas during the proliferative phase of the menstrual cycle. J Clin Endocrinol Metab. 1994; 79(3): 900–6.
65.
Sozen I, Arici A. Interactions of cytokines, growth factors, and the extracellular matrix in the cellular biology of uterine leiomyomata. Fertil Steril. 2002; 78(1): 1–12.
66.
Malik M, Catherino WH. Novel method to characterize primary cultures of leiomyoma and myometrium with the use of confirmatory biomarker gene arrays. Fertil Steril. 2007; 87(5): 1166–72.
67.
Halder SK, Osteen KG, Al-Hendy A. Vitamin D3 inhibits expression and activities of matrix metalloproteinase-2 and -9 in human uterine fibroid cells. Hum Reprod. 2013; 28(9): 2407–16.
68.
Ozkan S, Jindal S, Greenseid K, Shu J, Zeitlian G, Hickmon C, et al. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril. 2010; 94(4): 1314–9.
69.
Garbedian K, Boggild M, Moody J, Liu KE. Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization. CMAJ Open. 2013; 1(2): E77–E82.
70.
Polyzos NP, Anckaert E, Guzman L, Schiettecatte J, Van Landuyt L, Camus M, et al. Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI. Human Reproduction. 2014; 29(9): 2032–40.
71.
Rudick BJ, Ingles SA, Chung K, Stanczyk FZ, Paulson RJ, Bendikson KA. Influence of vitamin D levels on in vitro fertilization outcomes in donor-recipient cycles. Fertil Steril. 2014; 101(2): 447–52.
72.
Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Human Reproduction. 2012; 27(11): 3321–7.
73.
Aleyasin A, Hosseini MA, Mahdavi A, Safdarian L, Fallahi P, Mohajeri MR, et al. Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology. Eur J Obstet Gynecol Reprod Biol. 2011; 159(1): 132–7.
74.
Franasiak JM, Molinaro TA, Dubell EK, Scott KL, Ruiz AR, Forman EJ, et al. Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts. American Journal of Obstetrics and Gynecology. 2015; 212(3): 315.e1–315.e6.
75.
Firouzabadi RD, Rahmani E, Rahsepar M, Firouzabadi MM. Value of follicular fluid vitamin D in predicting the pregnancy rate in an IVF program. Arch Gynecol Obstet. 2014; 289(1): 201–6.
76.
Lv SS, Wang JY, Wang XQ, Wang Y, Xu Y. Serum vitamin D status and in vitro fertilization outcomes: a systematic review and meta-analysis. Archives of Gynecology and Obstetrics. 2016; 293(6): 1339–45.
77.
Van de Vijver A, Drakopoulos P, Van Landuyt L, Vaiarelli A, Blockeel C, Santos-Ribeiro S, et al. Vitamin D deficiency and pregnancy rates following frozen–thawed embryo transfer: a prospective cohort study. Human Reproduction. 2016; 31(8): 1749–54.
78.
Anifandis GM, Dafopoulos K, Messini CI, Chalvatzas N, Liakos N, Pournaras S, et al. Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reproductive Biology and Endocrinology. 2010; 8(1): 91.
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