Abstract
In recent years the interest in vitamin D is steadily growing. Numerous scientific publications and health guidebooks for the public have been published. Besides the well-known effects on calcium and bone metabolism, a positive impact of the sunshine vitamin on human wellbeing and health has been proposed. A high prevalence of vitamin D deficiency according to established optimal values has been described, although no increase of the classical diseases associated with vitamin D deficiency, e.g., rachitis and osteomalacia, has been observed. Besides infants and the elderly, populations at risk include women of childbearing age. The discovery that human tissues with a role in reproductive function, e.g., ovaries, endometrium, and placenta, express the vitamin D receptor and enzymes involved in vitamin D metabolism, has provoked studies on the role of vitamin D in reproductive health. While observational studies suggest an association between low vitamin D status and impaired reproductive outcomes, there are only few high quality randomized clinical trials available that could prove causality. This chapter summarizes the current knowledge on vitamin D metabolism, epidemiology, and treatment of vitamin D deficiency with focus on women’s reproductive health.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
Abbreviations
- aOR:
-
Adjusted odds ratio
- AFC:
-
Antral follicle count
- AMH:
-
Anti-mullerian hormone
- CI:
-
Confidence interval
- DBP:
-
Vitamin D-binding protein
- 7-(DHC):
-
7-Dehydrocholesterol
- DGE:
-
German Nutrition Society
- FSH:
-
Follicle stimulating hormone
- 25(OH)D:
-
25-Hydroxyvitamin D
- 1,25(OH)2D:
-
1,25-Dihydoxyvitamin D
- IL-8:
-
Interleukin-8
- IR:
-
Insulin resistance
- IOM:
-
Institute of Medicine
- IVF:
-
In vitro-fertilization
- LH:
-
Luteinising hormone
- PCOS:
-
Polycystic ovary syndrome
- PTH:
-
Parathyroid hormone
- RCT:
-
Randomized controlled trial
- RDA:
-
Recommended dietary allowance
- RXR:
-
Retinoic acid receptor
- VDR:
-
Vitamin D receptor
References
Agic A, Xu H, Altgassen C, Noack F, Wolfler MM, Diedrich K, Friedrich M, Taylor RN, Hornung D (2007) 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 14(5):486–497. https://doi.org/10.1177/1933719107304565
Ahn SH, Monsanto SP, Miller C, Singh SS, Thomas R, Tayade C (2015) Pathophysiology and immune dysfunction in endometriosis. Biomed Res Int 2015:795976. https://doi.org/10.1155/2015/795976
Aleyasin A, Hosseini MA, Mahdavi A, Safdarian L, Fallahi P, Mohajeri MR, Abbasi M, Esfahani F (2011.: Epub ahead of print) Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology. Eur J Obstet Gynecol Reprod Biol. https://doi.org/10.1016/j.ejogrb.2011.07.006
Anifandis GM, Dafopoulos K, Messini CI, Chalvatzas N, Liakos N, Pournaras S, Messinis IE (2010) Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reprod Biol Endocrinol 8:91. https://doi.org/10.1186/1477-7827-8-91
Baran DT, Whyte MP, Haussler MR, Deftos LJ, Slatopolsky E, Avioli LV (1980) Effect of the menstrual cycle on calcium-regulating hormones in the normal young woman. J Clin Endocrinol Metab 50(2):377–379
Barrera D, Avila E, Hernandez G, Mendez I, Gonzalez L, Halhali A, Larrea F, Morales A, Diaz L (2008) Calcitriol affects hCG gene transcription in cultured human syncytiotrophoblasts. Reprod Biol Endocrinol 6:3. https://doi.org/10.1186/1477-7827-6-3
Berger VK, Baker VL (2014) Preimplantation diagnosis for single gene disorders. Semin Reprod Med 32(2):107–113. https://doi.org/10.1055/s-0033-1363552
Bikle DD (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21(3):319–329. https://doi.org/10.1016/j.chembiol.2013.12.016
Böhles HJ, Fusch C, Genzel-Boroviczény O, Jochum F, Kauth T, Kersting M, Koletzko B, Lentze MJ, Moß AG, Mihatsch WA, Przyrembel H, Schnabel DG, Wabitsch M (2011) Vitamin-D-Versorgung im Säuglings-, Kindes- und Jugendalter. Monatsschr Kinderheilkd 159(11):1084–1084. https://doi.org/10.1007/s00112-011-2535-y
Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, Lieben L, Mathieu C, Demay M (2008) Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev 29(6):726–776. https://doi.org/10.1210/er.2008-0004. er.2008-0004 [pii]
Buchanan JR, Santen R, Cauffman S, Cavaliere A, Greer RB, Demers LM (1986) The effect of endogenous estrogen fluctuation on metabolism of 25-hydroxyvitamin D. Calcif Tissue Int 39(3):139–144
Chiu KC, Chuang LM, Yoon C (2001) The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians. BMC Med Genet 2:2
Christakos S, Ajibade DV, Dhawan P, Fechner AJ, Mady LJ (2010) Vitamin D: metabolism. Endocrinol Metab Clin North Am 39(2):243–253. https://doi.org/10.1016/j.ecl.2010.02.002
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G (2016) Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev 96(1):365–408. https://doi.org/10.1152/physrev.00014.2015
D-A-CH Referenzwerte für die Nährstoffzufuhr. 3.korrigierte Auflage, Nachdruck, Frankfurt am Main:Umschau/Braus: Deutsche Gesellschaft für Ernährung (DGE), Österreichische Gesellschaft für Ernährung (ÖGE), Schweizerische Gesellschaft für Ernährungsforschung (SGE), Schweizerische Vereinigung für Ernährung (SVE). DGE-Medienservice. 2008
Dicken CL, Israel DD, Davis JB, Sun Y, Shu J, Hardin J, Neal-Perry G (2012) Peripubertal vitamin D(3) deficiency delays puberty and disrupts the estrous cycle in adult female mice. Biol Reprod 87(2):51. https://doi.org/10.1095/biolreprod.111.096511
Dokoh S, Donaldson CA, Marion SL, Pike JW, Haussler MR (1983) The ovary: a target organ for 1,25-dihydroxyvitamin D3. Endocrinology 112(1):200–206
Drakopoulos P, van de Vijver A, Schutyser V, Milatovic S, Anckaert E, Schiettecatte J, Blockeel C, Camus M, Tournaye H, Polyzos NP (2017) The effect of serum vitamin D levels on ovarian reserve markers: a prospective cross-sectional study. Hum Reprod 32(1):208–214. https://doi.org/10.1093/humrep/dew304
Dressler N, Chandra A, Aguirre Davila L, Spineli LM, Schippert C, von Versen-Hoynck F (2016) BMI and season are associated with vitamin D deficiency in women with impaired fertility: a two-centre analysis. Arch Gynecol Obstet 293(4):907–914. https://doi.org/10.1007/s00404-015-3950-4
Dunaif A, Segal KR, Futterweit W, Dobrjansky A (1989) Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes 38(9):1165–1174
Eskenazi B, Warner ML (1997) Epidemiology of endometriosis. Obstet Gynecol Clin North Am 24(2):235–258
Faserl K, Golderer G, Kremser L, Lindner H, Sarg B, Wildt L, Seeber B (2011) Polymorphism in vitamin D-binding protein as a genetic risk factor in the pathogenesis of endometriosis. J Clin Endocrinol Metab 96(1):E233–E241. https://doi.org/10.1210/jc.2010-1532
Fischer D, Thome M, Becker S, Cordes T, Diedrich K, Friedrich M, Thill M (2009) 25-Hydroxyvitamin D3 1alpha-hydroxylase splice variants in benign and malignant ovarian cell lines and tissue. Anticancer Res 29(9):3627–3633
Franasiak JM, Molinaro TA, Dubell EK, Scott KL, Ruiz AR, Forman EJ, Werner MD, Hong KH, Scott RT Jr (2015) Vitamin D levels do not affect IVF outcomes following the transfer of euploid blastocysts. Am J Obstet Gynecol 212(3):315.e311–315.e316. https://doi.org/10.1016/j.ajog.2014.09.029
Franasiak JM, Wang X, Molinaro TA, Green K, Sun W, Werner MD, Juneau CR, Scott RT (2016) Free vitamin D does not vary through the follicular phase of the menstrual cycle. Endocrine 53(1):322–326. https://doi.org/10.1007/s12020-016-0946-1
German Nutrition Society (DGE) (2012) New Reference Values for Vitamin D. Annals of Nutrition and Metabolism 60 (4):241-246
Grant WB, Holick MF (2005) Benefits and requirements of vitamin D for optimal health: a review. Altern Med Rev 10(2):94–111
Gray TK, McAdoo T, Hatley L, Lester GE, Thierry M (1982) Fluctuation of serum concentration of 1,25-dihydroxyvitamin D3 during the menstrual cycle. Am J Obstet Gynecol 144(8):880–884. https://doi.org/10.1016/0002-9378(82)90177-6
Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA (2013) Dairy-food, calcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort study. Am J Epidemiol 177(5):420–430. https://doi.org/10.1093/aje/kws247
Holick MF 2002 Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Curr Opin Endocrinol Diabetes Obes 9(1):87–98
Holick MF (2009) Vitamin D status: measurement, interpretation, and clinical application. Ann Epidemiol 19(2):73–78. https://doi.org/10.1016/j.annepidem.2007.12.001
Institute of Medicine (1999) Food and Nutrition Board: Dietary reference intakes: calcium, phosphorus. magnesium, vitamin D and fluoride. National Academy Press, Washington, DC
Institute of Medicine (2010) Food and nutrition board: dietary reference intakes for calcium and vitamin D. National Academy Press, Washington, DC
Jukic AM, Steiner AZ, Baird DD (2015) Lower plasma 25-hydroxyvitamin D is associated with irregular menstrual cycles in a cross-sectional study. Reprod Biol Endocrinol 13:20. https://doi.org/10.1186/s12958-015-0012-5
Jukic AM, Upson K, Harmon QE, Baird DD (2016) Increasing serum 25-hydroxyvitamin D is associated with reduced odds of long menstrual cycles in a cross-sectional study of African American women. Fertil Steril 106(1):172–179.e172. https://doi.org/10.1016/j.fertnstert.2016.03.004
Kamphuis EI, Bhattacharya S, van der Veen F, Mol BW, Templeton A, Evidence Based IVF Group (2014) Are we overusing IVF? BMJ 348:g252. https://doi.org/10.1136/bmj.g252
Krul-Poel YH, Snackey C, Louwers Y, Lips P, Lambalk CB, Laven JS, Simsek S (2013) The role of vitamin D in metabolic disturbances in polycystic ovary syndrome: a systematic review. Eur J Endocrinol 169(6):853–865. https://doi.org/10.1530/eje-13-0617
Lanham-New SA, Buttriss JL, Miles LM, Ashwell M, Berry JL, Boucher BJ, Cashman KD, Cooper C, Darling AL, Francis RM, Fraser WD, de Groot CP, Hypponen E, Kiely M, Lamberg-Allardt C, Macdonald HM, Martineau AR, Masud T, Mavroeidi A, Nowson C, Prentice A, Stone EM, Reddy S, Vieth R, Williams CM (2011) Proceedings of the rank forum on vitamin D. Br J Nutr 105(1):144–156. https://doi.org/10.1017/S0007114510002576
Lasco A, Catalano A, Benvenga S (2012) Improvement of primary dysmenorrhea caused by a single oral dose of vitamin D: results of a randomized, double-blind, placebo-controlled study. Arch Intern Med 172(4):366–367. https://doi.org/10.1001/archinternmed.2011.715
Lerchbaum E, Obermayer-Pietsch B (2012) Vitamin D and fertility: a systematic review. Eur J Endocrinol 166(5):765–778. https://doi.org/10.1530/EJE-11-0984
Liu E, Meigs JB, Pittas AG, McKeown NM, Economos CD, Booth SL, Jacques PF (2009) Plasma 25-hydroxyvitamin d is associated with markers of the insulin resistant phenotype in nondiabetic adults. J Nutr 139(2):329–334. https://doi.org/10.3945/jn.108.093831
Loomis WF (1967) Skin-pigment regulation of vitamin-D biosynthesis in man. Science 157(3788):501–506
Lv SS, Wang JY, Wang XQ, Wang Y, Xu Y (2016) Serum vitamin D status and in vitro fertilization outcomes: a systematic review and meta-analysis. Arch Gynecol Obstet 293(6):1339–1345. https://doi.org/10.1007/s00404-016-4058-1
Mahmoudi T (2009) Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk. Fertil Steril 92(4):1381–1383. https://doi.org/10.1016/j.fertnstert.2009.05.002. S0015-0282(09)01071-1 [pii]
Merhi ZO, Seifer DB, Weedon J, Adeyemi O, Holman S, Anastos K, Golub ET, Young M, Karim R, Greenblatt R, Minkoff H (2012) Circulating vitamin D correlates with serum antimullerian hormone levels in late-reproductive-aged women: women’s interagency HIV study. Fertil Steril 98(1):228–234. https://doi.org/10.1016/j.fertnstert.2012.03.029
Merhi Z, Doswell A, Krebs K, Cipolla M (2014) Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells. J Clin Endocrinol Metab 99(6):E1137–E1145. https://doi.org/10.1210/jc.2013-4161
Muse KN, Manolagas SC, Deftos LJ, Alexander N, Yen SS (1986) Calcium-regulating hormones across the menstrual cycle. J Clin Endocrinol Metab 62(6):1313–1316
Need AG, Morris HA, Horowitz M, Nordin C (1993) Effects of skin thickness, age, body fat, and sunlight on serum 25-hydroxyvitamin D. Am J Clin Nutr 58(6):882–885
Ozkan S, Jindal S, Greenseid K, Shu J, Zeitlian G, Hickmon C, Pal L (2010) Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril 94(4):1314–1319. https://doi.org/10.1016/j.fertnstert.2009.05.019. S0015-0282(09)01095-4 [pii]
Paffoni A, Ferrari S, Vigano P, Pagliardini L, Papaleo E, Candiani M, Tirelli A, Fedele L, Somigliana E (2014) Vitamin D deficiency and infertility: insights from in vitro fertilization cycles. J Clin Endocrinol Metab 99(11):E2372–E2376. https://doi.org/10.1210/jc.2014-1802
Pagliardini L, Vigano P, Molgora M, Persico P, Salonia A, Vailati SH, Paffoni A, Somigliana E, Papaleo E, Candiani M (2015) High prevalence of vitamin D deficiency in infertile women referring for assisted reproduction. Nutrients 7(12):9972–9984. https://doi.org/10.3390/nu7125516
Panda DK, Miao D, Tremblay ML, Sirois J, Farookhi R, Hendy GN, Goltzman D (2001) Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc Natl Acad Sci U S A 98(13):7498–7503. https://doi.org/10.1073/pnas.131029498
Parikh G, Varadinova M, Suwandhi P, Araki T, Rosenwaks Z, Poretsky L, Seto-Young D (2010) Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm Metab Res 42(10):754–757. https://doi.org/10.1055/s-0030-1262837
Perez-Fernandez R, Alonso M, Segura C, Munoz I, Garcia-Caballero T, Diguez C (1997) Vitamin D receptor gene expression in human pituitary gland. Life Sci 60(1):35–42
Pitkin RM, Reynolds WA, Williams GA, Hargis GK (1978) Calcium-regulating hormones during the menstrual cycle. J Clin Endocrinol Metab 47(3):626–632
Polyzos NP, Anckaert E, Guzman L, Schiettecatte J, Van Landuyt L, Camus M, Smitz J, Tournaye H (2014) Vitamin D deficiency and pregnancy rates in women undergoing single embryo, blastocyst stage, transfer (SET) for IVF/ICSI. Hum Reprod 29(9):2032–2040. https://doi.org/10.1093/humrep/deu156
Potashnik G, Lunenfeld E, Levitas E, Itskovitz J, Albutiano S, Yankowitz N, Sonin Y, Levy J, Glezerman M, Shany S (1992) The relationship between endogenous oestradiol and vitamin D3 metabolites in serum and follicular fluid during ovarian stimulation for in-vitro fertilization and embryo transfer. Hum Reprod 7(10):1357–1360
Ranjzad F, Mahban A, Irani Shemirani A, Mahmoudi T, Vahedi M, Nikzamir A, Zali MR (2010) Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet 28:225–232. https://doi.org/10.1007/s10815-010-9506-4 [doi]
Ranjzad F, Mahmoudi T, Irani Shemirani A, Mahban A, Nikzamir A, Vahedi M, Ashrafi M, Gourabi H (2011) A common variant in the adiponectin gene and polycystic ovary syndrome risk. Mol Biol Rep. https://doi.org/10.1007/s11033-011-0981-1. Epub ahead of print
Rojansky N, Brzezinski A, Schenker JG (1992) Seasonality in human reproduction: an update. Hum Reprod 7(6):735–745
Ross AC (2011) The 2011 report on dietary reference intakes for calcium and vitamin D. Public Health Nutr 14(5):938–939. https://doi.org/10.1017/S1368980011000565
Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K (2012) Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod 27(11):3321–3327. https://doi.org/10.1093/humrep/des280
Rudick BJ, Ingles SA, Chung K, Stanczyk FZ, Paulson RJ, Bendikson KA (2014) Influence of vitamin D levels on in vitro fertilization outcomes in donor-recipient cycles. Fertil Steril 101(2):447–452. https://doi.org/10.1016/j.fertnstert.2013.10.008
Scragg R, Sowers M, Bell C (2004) Serum 25-hydroxyvitamin D, diabetes, and ethnicity in the third national health and nutrition examination survey. Diabetes Care 27(12):2813–2818
Somigliana E, Panina-Bordignon P, Murone S, Di Lucia P, Vercellini P, Vigano P (2007) Vitamin D reserve is higher in women with endometriosis. Hum Reprod 22(8):2273–2278. https://doi.org/10.1093/humrep/dem142
Sun T, Zhao Y, Mangelsdorf DJ, Simpson ER (1998) Characterization of a region upstream of exon I.1 of the human CYP19 (aromatase) gene that mediates regulation by retinoids in human choriocarcinoma cells. Endocrinology 139(4):1684–1691
Tamblyn JA, Susarla R, Jenkinson C, Jeffery LE, Ohizua O, Chun RF, Chan SY, Kilby MD, Hewison M (2017) Dysregulation of maternal and placental vitamin D metabolism in preeclampsia. Placenta 50:70–77. https://doi.org/10.1016/j.placenta.2016.12.019
Thierfelder W, Roth HJ, Laussmann D, Pientka L, Schumacher J, Schulz J (2008) Vitamin D and parathyoid hormone: a tool to determine assay-specific cutoff values for vitamin D. J Lab Med 32(6): 456-463. https://doi.org/10.1515/JLM.2008.060et
Thill M, Becker S, Fischer D, Cordes T, Hornemann A, Diedrich K, Salehin D, Friedrich M (2009) Expression of prostaglandin metabolising enzymes COX-2 and 15-PGDH and VDR in human granulosa cells. Anticancer Res 29(9):3611–3618
Tjellesen L, Christiansen C, Hummer L, Larsen NE (1983) Unchanged biochemical indices of bone turnover despite fluctuations in 1,25-dihydroxyvitamin D during the menstrual cycle. Acta Endocrinol 102(3):476–480
Unholzer S, Rothmund A, Haen E (2017) All-rounder vitamin D? Nervenarzt 88:489. https://doi.org/10.1007/s00115-016-0278-7
USDA Food Composition Databases (1889) United States Department of Agriculture, Beltsville. https://ndb.nal.usda.gov/ndb/. Accessed 1 Mar 2017
Vigano P, Lattuada D, Mangioni S, Ermellino L, Vignali M, Caporizzo E, Panina-Bordignon P, Besozzi M, Di Blasio AM (2006) Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system. J Mol Endocrinol 36(3):415–424. https://doi.org/10.1677/jme.1.01946
Wehr E, Pilz S, Boehm BO, Marz W, Obermayer-Pietsch B (2010) Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf) 73(2):243–248. https://doi.org/10.1111/j.1365-2265.2009.03777.x
Wehr E, Trummer O, Giuliani A, Gruber HJ, Pieber TR, Obermayer-Pietsch B (2011) Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 164(5):741–749. https://doi.org/10.1530/EJE-11-0134
Zarei S, Mohammad-Alizadeh-Charandabi S, Mirghafourvand M, Javadzadeh Y, Effati-Daryani F (2016) Effects of calcium-vitamin D and calcium-alone on pain intensity and menstrual blood loss in women with primary dysmenorrhea: a randomized controlled trial. Pain Med. https://doi.org/10.1093/pm/pnw121
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this entry
Cite this entry
Schröder-Heurich, B., von Versen-Höynck, F. (2019). Vitamin D Deficiency and Fertility: An Overview. In: Preedy, V., Patel, V. (eds) Handbook of Famine, Starvation, and Nutrient Deprivation. Springer, Cham. https://doi.org/10.1007/978-3-319-55387-0_44
Download citation
DOI: https://doi.org/10.1007/978-3-319-55387-0_44
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-55386-3
Online ISBN: 978-3-319-55387-0
eBook Packages: MedicineReference Module Medicine