RSS-Feed abonnieren
DOI: 10.1055/s-0036-1583529
Vitamin D in Reproductive Health and Pregnancy
Publikationsverlauf
Publikationsdatum:
26. Mai 2016 (online)
![](https://www.thieme-connect.de/media/srm/201602/lookinside/thumbnails/10-1055-s-0036-1583529_001009-1.jpg)
Abstract
Vitamin D has been primarily known for its role in maintaining calcium and phosphorus homeostasis and promoting healthy bone mineralization. Emerging evidence suggests that vitamin D may have a plethora of other functions including cardiometabolic and immunological effects and a role in modulating human reproductive processes. Despite this, vitamin D deficiency (VDD) remains highly prevalent worldwide due to the limited availability of foods that are naturally high or fortified with vitamin D, increased sun avoidance behaviors and use of sunscreen due to fear of skin cancer, and increased sedentary indoor lifestyles, especially among those of reproductive age. This review examines current and emerging evidence for the role of vitamin D in reproductive health including in fertility, conception, and pregnancy outcomes, and outlines areas for future research. We found that existing evidence is based primarily on animal models and in vitro studies with some recent support from observational studies in humans. While these studies indicate that VDD may be a risk factor for adverse fertility and pregnancy outcomes, there is insufficient evidence to establish causality. Future efforts to clarify the benefits of vitamin D in reproductive health may bring about practical, simple, and cost-effective means of improving fertility and pregnancy outcomes.
-
References
- 1 Moon RJ, Harvey NC, Cooper C. Endocrinology In Pregnancy: Influence of maternal vitamin D status on obstetric outcomes and the fetal skeleton. Eur J Endocrinol 2015; 173 (2) R69-R83
- 2 Flood-Nichols SK, Tinnemore D, Huang RR, Napolitano PG, Ippolito DL. Vitamin D deficiency in early pregnancy. PLoS ONE 2015; 10 (4) e0123763
- 3 van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab 2011; 25 (4) 671-680
- 4 Dabrowski FA, Grzechocinska B, Wielgos M. The role of vitamin D in reproductive health—a Trojan Horse or the Golden Fleece?. Nutrients 2015; 7 (6) 4139-4153
- 5 Forti G, Krausz C. Clinical review 100: Evaluation and treatment of the infertile couple. J Clin Endocrinol Metab 1998; 83 (12) 4177-4188
- 6 Jørgensen N, Asklund C, Carlsen E, Skakkebaek NE. Coordinated European investigations of semen quality: results from studies of Scandinavian young men is a matter of concern. Int J Androl 2006; 29 (1) 54-61 , discussion 105–108
- 7 Blomberg Jensen M. Vitamin D and male reproduction. Nat Rev Endocrinol 2014; 10 (3) 175-186
- 8 Yan W-J, Yu N, Yin T-L, Liu L, Yang J. Can Vitamin D supplementation be used as adjunctive treatment for oligozoospermia or asthenozoospermia accompanied with Vitamin D deficiency?. Asian J Androl 2015; 17 (1) 165-167
- 9 Blomberg Jensen M, Bjerrum PJ, Jessen TE , et al. Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Hum Reprod 2011; 26 (6) 1307-1317
- 10 Wehr E, Pilz S, Boehm BO, März W, Obermayer-Pietsch B. Association of vitamin D status with serum androgen levels in men. Clin Endocrinol (Oxf) 2010; 73 (2) 243-248
- 11 Ramlau-Hansen CH, Moeller UK, Bonde JP, Olsen J, Thulstrup AM. Are serum levels of vitamin D associated with semen quality? Results from a cross-sectional study in young healthy men. Fertil Steril 2011; 95 (3) 1000-1004
- 12 Hammoud AO, Meikle AW, Peterson CM, Stanford J, Gibson M, Carrell DT. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J Androl 2012; 14 (6) 855-859
- 13 Joham AE, Teede HJ, Cassar S , et al. Vitamin D in polycystic ovary syndrome: Relationship to obesity and insulin resistance. Mol Nutr Food Res 2016; 60 (1) 110-118
- 14 Teede HJ, Hutchison SK, Zoungas S. The management of insulin resistance in polycystic ovary syndrome. Trends Endocrinol Metab 2007; 18 (7) 273-279
- 15 Diamanti-Kandarakis E, Papavassiliou AG. Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med 2006; 12 (7) 324-332
- 16 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) 2017-2029
- 17 He C, Lin Z, Robb SW, Ezeamama AE. Serum Vitamin D Levels and Polycystic Ovary syndrome: A Systematic Review and Meta-Analysis. Nutrients 2015; 7 (6) 4555-4577
- 18 Mahmoudi T. Genetic variation in the vitamin D receptor and polycystic ovary syndrome risk. Fertil Steril 2009; 92 (4) 1381-1383
- 19 Hahn S, Haselhorst U, Tan 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) 577-583
- 20 Muscogiuri G, Policola C, Prioletta A , et al. Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS?. Clin Nutr 2012; 31 (4) 476-480
- 21 Yildizhan R, Kurdoglu M, Adali E , et al. Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet 2009; 280 (4) 559-563
- 22 Velija-Ašimi Z. Evaluation of the association of vitamin D deficiency with gonadotropins and sex hormone in obese and non-obese women with polycystic ovary syndrome. Med Glas (Zenica) 2014; 11 (1) 170-176
- 23 Thomson RL, Spedding S, Buckley JD. Vitamin D in the aetiology and management of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2012; 77 (3) 343-350
- 24 Wehr E, Pilz S, Schweighofer N , et al. Association of hypovitaminosis D with metabolic disturbances in polycystic ovary syndrome. Eur J Endocrinol 2009; 161 (4) 575-582
- 25 Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil Steril 2014; 102 (2) 460-468.e3
- 26 Sollis SS. Vitamin D Deficiency and Infertility: A Systematic Review. In, College of Nursing. Provo: Brigham Young University; 2015: 20
- 27 Ott J, Wattar L, Kurz C , et al. Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study. Eur J Endocrinol 2012; 166 (5) 897-902
- 28 Asadi M, Matin N, Frootan M, Mohamadpour J, Qorbani M, Tanha FD. Vitamin D improves endometrial thickness in PCOS women who need intrauterine insemination: a randomized double-blind placebo-controlled trial. Arch Gynecol Obstet 2014; 289 (4) 865-870
- 29 Firouzabadi Rd, Aflatoonian A, Modarresi S, Sekhavat L, MohammadTaheri S. Therapeutic effects of calcium & vitamin D supplementation in women with PCOS. Complement Ther Clin Pract 2012; 18 (2) 85-88
- 30 Wehr E, Pieber TR, Obermayer-Pietsch B. Effect of vitamin D3 treatment on glucose metabolism and menstrual frequency in polycystic ovary syndrome women: a pilot study. J Endocrinol Invest 2011; 34 (10) 757-763
- 31 Rashidi B, Haghollahi F, Shariat M, Zayerii F. The effects of calcium-vitamin D and metformin on polycystic ovary syndrome: a pilot study. Taiwan J Obstet Gynecol 2009; 48 (2) 142-147
- 32 Lerchbaum E, Obermayer-Pietsch B. Vitamin D and fertility: a systematic review. Eur J Endocrinol 2012; 166 (5) 765-778
- 33 CDC. 2012 Assisted Reproductive Technology National Summary Report. In: Prevention CfDCa ed. Atlanta, GA: US Dept of Health and Human Services; 2012
- 34 Ozkan S, Jindal S, Greenseid K , et al. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril 2010; 94 (4) 1314-1319
- 35 Anifandis GM, Dafopoulos K, Messini CI , et al. Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reprod Biol Endocrinol 2010; 8: 91
- 36 Aleyasin A, Hosseini MA, Mahdavi A , 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) 132-137
- 37 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) 201-206
- 38 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) 447-452
- 39 Rudick B, Ingles S, Chung K, Stanczyk F, Paulson R, Bendikson K. Characterizing the influence of vitamin D levels on IVF outcomes. Hum Reprod 2012; 27 (11) 3321-3327
- 40 Yeow TP, Lim SL, Hor CP, Khir AS, Wan Mohamud WN, Pacini G. Impact of Vitamin D Replacement on Markers of Glucose Metabolism and Cardio-Metabolic Risk in Women with Former Gestational Diabetes—A Double-Blind, Randomized Controlled Trial. PLoS ONE 2015; 10 (6) e0129017
- 41 Abell SK, De Courten B, Boyle JA, Teede HJ. Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus. Int J Mol Sci 2015; 16 (6) 13442-13473
- 42 Zhang MX, Pan GT, Guo JF, Li BY, Qin LQ, Zhang ZL. Vitamin D Deficiency Increases the Risk of Gestational Diabetes Mellitus: A Meta-Analysis of Observational Studies. Nutrients 2015; 7 (10) 8366-8375
- 43 Ramos-Lopez E, Kahles H, Weber S , et al. Gestational diabetes mellitus and vitamin D deficiency: genetic contribution of CYP27B1 and CYP2R1 polymorphisms. Diabetes Obes Metab 2008; 10 (8) 683-685
- 44 Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O'Beirne M, Rabi DM. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and meta-analysis of observational studies. BMJ 2013; 346: f1169
- 45 Poel YH, Hummel P, Lips P, Stam F, van der Ploeg T, Simsek S. Vitamin D and gestational diabetes: a systematic review and meta-analysis. Eur J Intern Med 2012; 23 (5) 465-469
- 46 Wei SQ, Qi HP, Luo ZC, Fraser WD. Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 2013; 26 (9) 889-899
- 47 Schneuer FJ, Roberts CL, Guilbert C , et al. Effects of maternal serum 25-hydroxyvitamin D concentrations in the first trimester on subsequent pregnancy outcomes in an Australian population. Am J Clin Nutr 2014; 99 (2) 287-295
- 48 Asemi Z, Samimi M, Tabassi Z, Shakeri H, Esmaillzadeh A. Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women. J Nutr 2013; 143 (9) 1432-1438
- 49 Soheilykhah S, Mojibian M, Moghadam MJ, Shojaoddiny-Ardekani A. The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy. Gynecol Endocrinol 2013; 29 (4) 396-399
- 50 Karamali M, Beihaghi E, Mohammadi AA, Asemi Z. Effects of High-Dose Vitamin D Supplementation on Metabolic Status and Pregnancy Outcomes in Pregnant Women at Risk for Pre-Eclampsia. Horm Metab Res 2015; 47 (12) 867-872
- 51 Wagner CL, McNeil R, Hamilton SA , et al. A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina. Am J Obstet Gynecol 2013; 208 (2) 137.e1-137.e13
- 52 Yap C, Cheung NW, Gunton JE , et al. Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial. Diabetes Care 2014; 37 (7) 1837-1844
- 53 Pérez-López FR, Pasupuleti V, Mezones-Holguin E , et al. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and meta-analysis of randomized controlled trials. Fertil Steril 2015; 103 (5) 1278-88.e4
- 54 Hashemipour S, Ziaee A, Javadi A , et al. Effect of treatment of vitamin D deficiency and insufficiency during pregnancy on fetal growth indices and maternal weight gain: a randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 2014; 172: 15-19
- 55 Hossain N, Kanani FH, Ramzan S , et al. Obstetric and neonatal outcomes of maternal vitamin D supplementation: results of an open-label, randomized controlled trial of antenatal vitamin D supplementation in Pakistani women. J Clin Endocrinol Metab 2014; 99 (7) 2448-2455
- 56 Arain N, Mirza WA, Aslam M. Review-Vitamin D and the prevention of preeclampsia: A systematic review. Pak J Pharm Sci 2015; 28 (3) 1015-1021
- 57 Liu NQ, Hewison M. Vitamin D, the placenta and pregnancy. Arch Biochem Biophys 2012; 523 (1) 37-47
- 58 Hyppönen E, Cavadino A, Williams D , et al. Vitamin D and pre-eclampsia: original data, systematic review and meta-analysis. Ann Nutr Metab 2013; 63 (4) 331-340
- 59 Dawodu A, Akinbi H. Vitamin D nutrition in pregnancy: current opinion. Int J Womens Health 2013; 5: 333-343
- 60 Ito M, Koyama H, Ohshige A, Maeda T, Yoshimura T, Okamura H. Prevention of preeclampsia with calcium supplementation and vitamin D3 in an antenatal protocol. Int J Gynaecol Obstet 1994; 47 (2) 115-120
- 61 Cooper NA, Moores R ; East London Preterm Prevention Collaboration. A review of the literature regarding nutritional supplements and their effect on vaginal flora and preterm birth. Curr Opin Obstet Gynecol 2014; 26 (6) 487-492
- 62 Bodnar LM, Krohn MA, Simhan HN. Maternal vitamin D deficiency is associated with bacterial vaginosis in the first trimester of pregnancy. J Nutr 2009; 139 (6) 1157-1161
- 63 Harvey NC, Holroyd C, Ntani G , et al. Vitamin D supplementation in pregnancy: a systematic review. Health Technol Assess 2014; 18 (45) 1-190
- 64 Hossain N, Khanani R, Hussain-Kanani F, Shah T, Arif S, Pal L. High prevalence of vitamin D deficiency in Pakistani mothers and their newborns. Int J Gynaecol Obstet 2011; 112 (3) 229-233
- 65 Christesen HT, Falkenberg T, Lamont RF, Jørgensen JS. The impact of vitamin D on pregnancy: a systematic review. Acta Obstet Gynecol Scand 2012; 91 (12) 1357-1367
- 66 Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res 2011; 26 (10) 2341-2357
- 67 Menacker F, Declercq E, Macdorman MF. Cesarean delivery: background, trends, and epidemiology. Semin Perinatol 2006; 30 (5) 235-241
- 68 Scholl TO, Chen X, Stein P. Maternal vitamin D status and delivery by cesarean. Nutrients 2012; 4 (4) 319-330
- 69 Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF. Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab 2009; 94 (3) 940-945
- 70 Mohammad-Alizadeh-Charandabi S, Mirghafourvand M, Mansouri A, Najafi M, Khodabande F. The Effect of Vitamin D and Calcium plus Vitamin D during Pregnancy on Pregnancy and Birth Outcomes: a Randomized Controlled Trial. J Caring Sci 2015; 4 (1) 35-44
- 71 Karamali M, Asemi Z, Ahmadi-Dastjerdi M, Esmaillzadeh A. Calcium plus vitamin D supplementation affects pregnancy outcomes in gestational diabetes: randomized, double-blind, placebo-controlled trial. Public Health Nutr 2016; 19 (1) 156-163
- 72 Harris AL. Vitamin D deficiency and bacterial vaginosis in pregnancy: examining the link. Nurs Womens Health 2011; 15 (5) 423-430
- 73 Davis LM, Chang SC, Mancini J, Nathanson MS, Witter FR, O'Brien KO. Vitamin D insufficiency is prevalent among pregnant African American adolescents. J Pediatr Adolesc Gynecol 2010; 23 (1) 45-52
- 74 Dunlop AL, Taylor RN, Tangpricha V, Fortunato S, Menon R. Maternal vitamin D, folate, and polyunsaturated fatty acid status and bacterial vaginosis during pregnancy. Infect Dis Obstet Gynecol 2011; 2011: 216217
- 75 Hensel KJ, Randis TM, Gelber SE, Ratner AJ. Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. Am J Obstet Gynecol 2011; 204 (1) 41.e1-41.e9
- 76 Wagner CL, McNeil RB, Johnson DD , et al. Health characteristics and outcomes of two randomized vitamin D supplementation trials during pregnancy: a combined analysis. J Steroid Biochem Mol Biol 2013; 136: 313-320
- 77 Kalra P, Das V, Agarwal A , et al. Effect of vitamin D supplementation during pregnancy on neonatal mineral homeostasis and anthropometry of the newborn and infant. Br J Nutr 2012; 108 (6) 1052-1058
- 78 Marya RK, Rathee S, Dua V, Sangwan K. Effect of vitamin D supplementation during pregnancy on foetal growth. Indian J Med Res 1988; 88: 488-492
- 79 Marya RK, Rathee S, Lata V, Mudgil S. Effects of vitamin D supplementation in pregnancy. Gynecol Obstet Invest 1981; 12 (3) 155-161
- 80 Sørensen IM, Joner G, Jenum PA, Eskild A, Torjesen PA, Stene LC. Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring. Diabetes 2012; 61 (1) 175-178
- 81 Kriegel MA, Manson JE, Costenbader KH. Does vitamin D affect risk of developing autoimmune disease?: a systematic review. Semin Arthritis Rheum 2011; 40 (6) 512-531.e8
- 82 Dong JY, Zhang WG, Chen JJ, Zhang ZL, Han SF, Qin LQ. Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies. Nutrients 2013; 5 (9) 3551-3562
- 83 Miettinen ME, Reinert L, Kinnunen L , et al. Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring. Diabetologia 2012; 55 (5) 1291-1294
- 84 Lewis S, Lucas RM, Halliday J, Ponsonby AL. Vitamin D deficiency and pregnancy: from preconception to birth. Mol Nutr Food Res 2010; 54 (8) 1092-1102
- 85 Lapillonne A. Vitamin D deficiency during pregnancy may impair maternal and fetal outcomes. Med Hypotheses 2010; 74 (1) 71-75
- 86 Thys-Jacobs S, Donovan D, Papadopoulos A, Sarrel P, Bilezikian JP. Vitamin D and calcium dysregulation in the polycystic ovarian syndrome. Steroids 1999; 64 (6) 430-435
- 87 Palomer X, González-Clemente JM, Blanco-Vaca F, Mauricio D. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab 2008; 10 (3) 185-197
- 88 Burris HH, Rifas-Shiman SL, Kleinman K , et al. Vitamin D deficiency in pregnancy and gestational diabetes mellitus. Am J Obstet Gynecol 2012; 207 (3) 182.e1-182.e8
- 89 Reis JP, von Mühlen D, Kritz-Silverstein D, Wingard DL, Barrett-Connor E. Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care 2007; 30 (6) 1549-1555
- 90 Carbone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol 2014; 6 (5) 260-276
- 91 Triunfo S, Lanzone A. Potential impact of maternal vitamin D status on obstetric well-being. J Endocrinol Invest 2016; 39 (1) 37-44
- 92 Wagner CL, Taylor SN, Dawodu A, Johnson DD, Hollis BW. Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus. Nutrients 2012; 4 (3) 208-230
- 93 Kinuta K, Tanaka H, Moriwake T, Aya K, Kato S, Seino Y. Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology 2000; 141 (4) 1317-1324
- 94 Viganò P, Lattuada D, Mangioni S , et al. Cycling and early pregnant endometrium as a site of regulated expression of the vitamin D system. J Mol Endocrinol 2006; 36 (3) 415-424
- 95 Baker AM, Haeri S, Camargo Jr CA, Stuebe AM, Boggess KA. First-trimester maternal vitamin D status and risk for gestational diabetes (GDM) a nested case-control study. Diabetes Metab Res Rev 2012; 28 (2) 164-168
- 96 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) 227-232
- 97 Maestro B, Dávila N, Carranza MC, Calle C. Identification of a Vitamin D response element in the human insulin receptor gene promoter. J Steroid Biochem Mol Biol 2003; 84 (2–3) 223-230
- 98 Chopra S, Cherian D, Jacob JJ. The thyroid hormone, parathyroid hormone and vitamin D associated hypertension. Indian J Endocrinol Metab 2011; 15 (Suppl. 04) S354-S360
- 99 Bikle D. Nonclassic actions of vitamin D. J Clin Endocrinol Metab 2009; 94 (1) 26-34
- 100 Shin JS, Choi MY, Longtine MS, Nelson DM. Vitamin D effects on pregnancy and the placenta. Placenta 2010; 31 (12) 1027-1034
- 101 Gallagher JC, Sai AJ. Vitamin D insufficiency, deficiency, and bone health. J Clin Endocrinol Metab 2010; 95 (6) 2630-2633