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Assisted Reproduction – 5 studies concluded vitamin D repletion helps – Review March 2015

Vitamin D and assisted reproduction: should vitamin D be routinely screened and repleted prior to ART? A systematic review.

J Assist Reprod Genet. 2015 Mar;32(3):323-35. doi: 10.1007/s10815-014-0407-9. Epub 2014 Dec 30.
Pacis MM1, Fortin CN, Zarek SM, Mumford SL, Segars JH.
1Department of Obstetrics and Gynecology, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH, 03756, USA.


Vitamin D greatly improves Fertility

Increased male Vitamin D increases fertility

Decreased Fertility if decreased Vitamin D Receptor

 Download the PDF from VitaminDWiki

To review the current literature regarding the role of vitamin D status in pregnancy outcomes in women undergoing assisted reproductive technology (ART) and to assess cost-effectiveness of routine vitamin D deficiency screening and repletion prior to initiation of ART.

A systematic literature review was conducted using PubMed. Relevant study outcomes were compared among the selected studies. A cost-benefit analysis was performed using a decision tree mathematical model with sensitivity analyses from the perspective of direct societal cost. Published data were used to estimate probabilities and costs in 2014 US dollars.

Thirty-four articles were retrieved, of which eight met inclusion criteria. One study demonstrated a negative relationship between vitamin D status and ART outcomes, while two studies showed no association. The remaining five studies concluded that ART outcomes improved after vitamin D repletion.

The majority of reviewed studies reported a decrement in ART outcomes in patients with vitamin D deficiency. Cost-benefit analyses suggested that screening and supplementing vitamin D prior to ART might be cost effective, but further evidence is needed. Given the absence of Level I evidence regarding vitamin D status and ART outcomes, full endorsement of routine vitamin D screening and supplementation prior to ART is premature.

PMID: 25547950


  1. Bouillon, R, Carmeliet, G, Daci, E, Segaert, S, Verstuyf, A (1998) Vitamin D metabolism and action. Osteoporos Int 8: pp. S13-S19 CrossRef
  2. Norman, AW (2008) From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88: pp. 491S-499S
  3. Mitchell, DM, Henao, MP, Finkelstein, JS, Burnett-Bowie, SA (2012) Prevalence and predictors of vitamin D deficiency in healthy adults. Endocr Pract 18: pp. 914-923 CrossRef
  4. Looker, AC, Johnson, CL, Lacher, DA, Pfeiffer, CM, Schleicher, RL, Sempos, CT (2011) Vitamin D status: United States, 2001–2006. NCHS Data Brief 59: pp. 1-8
  5. Forrest, KYZ, Stuhldreher, WL (2011) Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res 31: pp. 48-54 CrossRef
  6. Kennel, KA, Drake, MT, Hurley, DL (2010) Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc 85: pp. 752-758 CrossRef
  7. Holick, MF, Binkley, NC, Bischoff-Ferrari, HA, Gordon, CM, Hanley, DA, Heaney, RP (2011) Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96: pp. 1911-1930 CrossRef
  8. Dietary reference intakes for calcium and vitamin D. National Academy Press, Washington, DC
  9. Vitamin D: screening and supplementation during pregnancy. Committee opinion no. 495. Obstet Gynecol 118: pp. 197-198 CrossRef
  10. Kwiecinski, GG, Petrie, GI, Deluca, HF (1989) Vitamin D is necessary for reproductive functions of the male rat. J Nutr 119: pp. 741-744
  11. Jensen, MB, Nielsen, JE, Jorgensen, A, Meyts, ER-D, Kristensen, DM, Jorgensen, N (2010) Vitamin D receptor and vitamin D metabolizing enzymes are expressed in the human male reproductive tract. Hum Reprod 25: pp. 1303-1311 CrossRef
  12. Johnson, JA, Grande, JP, Roche, PC, Kumar, R (1996) Immunohistochemical detection and distribution of the 1,25-dihydroxyvitamin D-3 receptor in rat reproductive tissues. Histochem Cell Biol 105: pp. 7-15 CrossRef
  13. Schleicher, G, Privette, TH, Stumpf, WE (1989) Distribuition of soltriol 1,25(OH)2-vitamin-D3 binding sites in male sex organs of the mouse: an autoradiographic study. J Histochem Cytochem 37: pp. 1083-1086 CrossRef
  14. Corbett, ST, Hill, O, Nangia, AK (2006) Vitamin D receptor found in human sperm. Urology 68: pp. 1345-1349 CrossRef
  15. Aquila, S, Guido, C, Perrotta, I, Tripepi, S, Nastro, A, Ando, S (2008) Human sperm anatomy: ultrastructural localization of 1 alpha,25-dihydroxyvitamin D(3) receptor and its possible role in the human male gamete. J Anat 213: pp. 555-564 CrossRef
  16. Jensen, MB, Bjerrum, PJ, Jessen, TE, Nielsen, JE, Joensen, UN, Olesen, IA (2011) Vitamin D is positively associated with sperm motility and increases intracellular calcium in human spermatozoa. Obstet Gynecol Surv 66: pp. 556-558 CrossRef
  17. Blomberg Jensen, M, Jorgensen, A, Nielsen, JE, Bjerrum, PJ, Skalkam, M, Petersen, JH (2012) Expression of the vitamin D metabolizing enzyme CYP24A1 at the annulus of human spermatozoa may serve as a novel marker of semen quality. Int J Androl 35: pp. 499-510 CrossRef
  18. Ramlau-Hansen, CH, Moeller, UK, Bonde, JP, Olsen, J, Thulstrup, AM (2011) Are serum levels of vitamin D associated with semen quality? Results from a cross-sectional study in young healthy men. Fertil Steril 95: pp. 1000-1004 CrossRef
  19. Hammoud, AO, Meikle, AW, Peterson, CM, Stanford, J, Gibson, M, Carrell, DT (2012) Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J Androl 14: pp. 855-859 CrossRef
  20. Adams, JS, Hewison, M (2008) Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab 4: pp. 80-90 CrossRef
  21. Ota, K, Dambaeva, S, Han, AR, Beaman, K, Gilman-Sachs, A, Kwak-Kim, J (2014) Vitamin D deficiency may be a risk factor for recurrent pregnancy losses by increasing cellular immunity and autoimmunity. Hum Reprod 29: pp. 208-219 CrossRef
  22. Andreoli, L, Piantoni, S, Dall’Ara, F, Allegri, F, Meroni, PL, Tincani, A (2012) Vitamin D and antiphospholipid syndrome. Lupus 21: pp. 736-740 CrossRef
  23. Tavakoli, M, Jeddi-Tehrani, M, Salek-Moghaddam, A, Rajaei, S, Mohammadzadeh, A, Sheikhhasani, S (2011) Effects of 1,25(OH)2 vitamin D3 on cytokine production by endometrial cells of women with recurrent spontaneous abortion. Fertil Steril 96: pp. 751-757 CrossRef
  24. Gysler SM, Mulla MJ, Stuhlman M, Sfakianaki AK, Paidas MJ, Stanwood NL, et al. Vitamin D reverses aPL-induced inflammation and LMWH-induced sFlt-1 release by human trophoblast. Am J Reprod Immunol. 2014.
  25. Bodnar, LM, Catov, JM, Simhan, HN, Holick, MF, Powers, RW, Roberts, JM (2007) Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 92: pp. 3517-3522 CrossRef
  26. Bodnar, LM, Catov, JM, Zmuda, JM, Cooper, ME, Parrott, MS, Roberts, JM (2010) Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr 140: pp. 999-1006 CrossRef
  27. Mannion, CA, Gray-Donald, K, Koski, KG (2006) Association of low intake of milk and vitamin D during pregnancy with decreased birth weight. CMAJ 174: pp. 1273-1277 CrossRef
  28. Brooke, OG, Brown, IRF, Bone, CDM, Carter, ND, Cleeve, HJW, Maxwell, JD (1980) Vitamin-D supplements in pregnant Asian women: effects on calcium status and fetal growth. BMJ 280: pp. 751-754 CrossRef
  29. Morley, R, Carlin, JB, Pasco, JA, Wark, JD (2006) Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Metab 91: pp. 906-912 CrossRef
  30. Merewood, A, Mehta, SD, Chen, TC, Bauchner, H, Holick, MF (2009) Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab 94: pp. 940-945 CrossRef
  31. Poel, YHM, Hummel, P, Lips, P, Stam, F, Ploeg, T, Simsek, S (2012) Vitamin D and gestational diabetes: a systematic review and meta-analysis. Eur J Intern Med 23: pp. 465-469 CrossRef
  32. Lebovic, DI, Mueller, MD, Taylor, RN (2001) Immunobiology of endometriosis. Fertil Steril 75: pp. 1-10 CrossRef
  33. Agic, A, Xu, H, Altgassen, C, Noack, F, Wolfler, MM, Diedrich, K (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: pp. 486-497 CrossRef
  34. Wortsman, J, Matsuoka, LY, Chen, TC, Lu, Z, Holick, MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72: pp. 690-693
  35. Goodarzi, MO, Dumesic, DA, Chazenbalk, G, Azziz, R (2011) Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7: pp. 219-231 CrossRef
  36. Girgis, CM, Clifton-Bligh, RJ, Hamrick, MW, Holick, MF, Gunton, JE (2013) The roles of vitamin D in skeletal muscle: form, function, and metabolism. Endocr Rev 34: pp. 33-83 CrossRef
  37. Mitri, J, Muraru, MD, Pittas, AG (2011) Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr 65: pp. 1005-1015 CrossRef
  38. Chiu, KC, Chu, A, Go, VL, Saad, MF (2004) Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am J Clin Nutr 79: pp. 820-825
  39. Tai, K, Need, AG, Horowitz, M, Chapman, IM (2008) Vitamin D, glucose, insulin, and insulin sensitivity. Nutrition 24: pp. 279-285 CrossRef
  40. Chiu, KC, Chuang, LM, Lee, NP, Ryu, JM, McGullam, JL, Tsai, GP (2000) Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone level. Metabolism 49: pp. 1501-1505 CrossRef
  41. McCarty, MF, Thomas, CA (2003) PTH excess may promote weight gain by impeding catecholamine-induced lipolysis-implications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypotheses 61: pp. 535-542 CrossRef
  42. Reis, JP, Muhlen, D, Kritz-Silverstein, D, Wingard, DL, Barrett-Connor, E (2007) Vitamin D, parathyroid hormone levels, and the prevalence of metabolic syndrome in community-dwelling older adults. Diabetes Care 30: pp. 1549-1555 CrossRef
  43. Maestro, B, Campion, J, Davila, N, Calle, C (2000) Stimulation by 1,25-dihydroxyvitamin D3 of insulin receptor expression and insulin responsiveness for glucose transport in U-937 human promonocytic cells. Endocr J 47: pp. 383-391 CrossRef
  44. Maestro, B, Davila, N, Carranza, MC, Calle, C (2003) Identification of a Vitamin D response element in the human insulin receptor gene promoter. J Steroid Biochem Mol Biol 84: pp. 223-230 CrossRef
  45. Kim, JJ, Choi, YM, Chae, SJ, Hwang, KR, Yoon, SH, Kim, MJ (2014) Vitamin D deficiency in women with polycystic ovary syndrome. Clin Exp Reprod Med 41: pp. 80-85 CrossRef
  46. 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: pp. 741-749 CrossRef
  47. Mazloomi, S, Sharifi, F, Hajihosseini, R, Kalantari, S, Mazloomzadeh, S (2012) Association between hypoadiponectinemia and low serum concentrations of calcium and vitamin D in women with polycystic ovary syndrome. ISRN Endocrinol 2012: pp. 949427
  48. Li, HW, Brereton, RE, Anderson, RA, Wallace, AM, Ho, CK (2011) Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism 60: pp. 1475-1481 CrossRef
  49. Mahmoudi, T, Gourabi, H, Ashrafi, M, Yazdi, RS, Ezabadi, Z (2010) Calciotropic hormones, insulin resistance, and the polycystic ovary syndrome. Fertil Steril 93: pp. 1208-1214 CrossRef
  50. Panidis, D, Balaris, C, Farmakiotis, D, Rousso, D, Kourtis, A, Balaris, V (2005) Serum parathyroid hormone concentrations are increased in women with polycystic ovary syndrome. Clin Chem 51: pp. 1691-1697 CrossRef
  51. Hahn, S, Haselhorst, U, Tan, S, Quadbeck, B, Schmidt, M, Roesler, S (2006) Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes 114: pp. 577-583 CrossRef
  52. Yildizhan, R, Kurdoglu, M, Adali, E, Kolusari, A, Yildizhan, B, Sahin, HG (2009) Serum 25-hydroxyvitamin D concentrations in obese and non-obese women with polycystic ovary syndrome. Arch Gynecol Obstet 280: pp. 559-563 CrossRef
  53. Lagunova, Z, Porojnicu, AC, Lindberg, F, Hexeberg, S, Moan, J (2009) The dependency of vitamin D status on body mass index, gender, age and season. Anticancer Res 29: pp. 3713-3720
  54. Merhi, Z (2014) Advanced glycation end products and their relevance in female reproduction. Hum Reprod 29: pp. 135-145 CrossRef
  55. Singh, R, Barden, A, Mori, T, Beilin, L (2001) Advanced glycation end-products: a review. Diabetologia 44: pp. 129-146 CrossRef
  56. Vazzana, N, Guagnano, MT, Cuccurullo, C, Ferrante, E, Lattanzio, S, Liani, R (2012) Endogenous secretory RAGE in obese women: association with platelet activation and oxidative stress. J Clin Endocrinol Metab 97: pp. E1726-E1730 CrossRef
  57. Unoki, H, Yamagishi, S (2008) Advanced glycation end products and insulin resistance. Curr Pharm Des 14: pp. 987-989 CrossRef
  58. Diamanti-Kandarakis, E, Piperi, C, Kalofoutis, A, Creatsas, G (2005) Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 62: pp. 37-43 CrossRef
  59. Diamanti-Kandarakis, E, Piperi, C, Patsouris, E, Korkolopoulou, P, Panidis, D, Pawelczyk, L (2007) Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem Cell Biol 127: pp. 581-589 CrossRef
  60. Jia, X, Chang, T, Wilson, TW, Wu, L (2012) Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1. PLoS One 7: pp. e36610 CrossRef
  61. Diamanti-Kandarakis, E, Piperi, C, Livadas, S, Kandaraki, E, Papageorgiou, E, Koutsilieris, M (2013) Interference of AGE-RAGE signaling with steroidogenic enzyme action in human ovarian cells. Endocrine Society, San Francisco
  62. Yoshizawa, T, Handa, Y, Uematsu, Y, Takeda, S, Sekine, K, Yoshihara, Y (1997) Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet 16: pp. 391-396 CrossRef
  63. Kinuta, K, Tanaka, H, Moriwake, T, Aya, K, Kato, S, Seino, Y (2000) Vitamin D is an important factor in estrogen biosynthesis of both female and male gonads. Endocrinology 141: pp. 1317-1324
  64. Halloran, BP, Deluca, HF (1980) Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat. J Nutr 110: pp. 1573-1580
  65. Liberati, A, Altman, DG, Tetzlaff, J, Mulrow, C, Gotzsche, PC, Ioannidis, JPA (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339: pp. b2700 CrossRef
  66. Firouzabadi, RD, Aflatoonian, A, Modarresi, S, Sekhavat, L, MohammadTaheri, S (2012) Therapeutic effects of calcium & vitamin D supplementation in women with PCOS. Complement Ther Clin Pract 18: pp. 85-88 CrossRef
  67. Aleyasin, A, Hosseini, MA, Mahdavi, A, Safdarian, L, Fallahi, P, Mohajeri, MR (2011) Predictive value of the level of vitamin D in follicular fluid on the outcome of assisted reproductive technology. Eur J Obstet Gynecol Reprod Biol 159: pp. 132-137 CrossRef
  68. Anifandis, GM, Dafopoulos, K, Messini, CI, Chalvatzas, N, Liakos, N, Pournaras, S (2010) Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reprod Bio Endocrinol 8: pp. 91 CrossRef
  69. Ozkan, S, Jindal, S, Greenseid, K, Shu, J, Zeitlian, G, Hickmon, C (2010) Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril 94: pp. 1314-1319 CrossRef
  70. 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: pp. 3321-3327 CrossRef
  71. Rudick, BJIS, 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: pp. 447-452 CrossRef
  72. Garbedian, KBM, Moody, J, Liu, K (2013) Effect of vitamin D status on clinical pregnancy rates following in vitro fertilization. CMAJ Open 1: pp. E77-E82 CrossRef
  73. 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. Hum Reprod. 2014.
  74. Consumer price index. Bureau of Labor Statistics, Washington, DC
  75. Centers for Medicare and Medicaid Services. 2014 clinical laboratory fee schedule. Baltimore, MD: Centers for Medicare and Medicaid Services, 2014. Available from: http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/ClinicalLabFeeSched/clinlab.html.
  76. Drug Price Search. https://www.rxpricequotes.com. Accessed 11 Aug 2014.
  77. Chambers, GM, Sullivan, EA, Ishihara, O, Chapman, MG, Adamson, GD (2009) The economic impact of assisted reproductive technology: a review of selected developed countries. Fertil Steril 91: pp. 2281-2294 CrossRef
  78. You, JH, Chung, TK (2005) Expectant, medical or surgical treatment for spontaneous abortion in first trimester of pregnancy: a cost analysis. Hum Reprod 20: pp. 2873-2878 CrossRef
  79. Bagot, CN, Troy, PJ, Taylor, HS (2000) Alteration of maternal Hoxa10 expression by in vivo gene transfection affects implantation. Gene Ther 7: pp. 1378-1384 CrossRef
  80. Vanni, VS, Vigano’, P, Somigliana, E, Papaleo, E, Paffoni, A, Pagliardini, L (2014) Vitamin D and assisted reproduction technologies: current concepts. Reprod Biol Endocrinol 12: pp. 47 CrossRef
  81. Purcell, K, Schembri, M, Frazier, LM, Rall, MJ, Shen, SH, Croughan, M (2007) Asian ethnicity is associated with reduced pregnancy outcomes after assisted reproductive technology. Fertil Steril 87: pp. 297-302 CrossRef
  82. Fujimoto, VY, Luke, B, Brown, MB, Jain, T, Armstrong, A, Grainger, DA (2010) Racial and ethnic disparities in assisted reproductive technology outcomes in the United States. Fertil Steril 93: pp. 382-390 CrossRef
  83. Gleicher, N, Weghofer, A, Li, J, Barad, D (2007) Differences in ovarian function parameters between Chinese and Caucasian oocyte donors: do they offer an explanation for lower IVF pregnancy rates in Chinese women?. Hum Reprod 22: pp. 2879-2882 CrossRef
  84. Gleicher, N, Kim, A, Weghofer, A, Barad, DH (2012) Differences in ovarian aging patterns between races are associated with ovarian genotypes and sub-genotypes of the FMR1 gene. Reprod Biol Endocrinol 10: pp. 77 CrossRef
  85. Karolinska University Hospital. Vitamin D during in vitro fertilisation (IVF)—a prospective randomized trial. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2014 Aug 17]. Available from: http://clinicaltrials.gov/show/NCT01019785 NLM Identifier: NCT01019785.
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