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.
- IVF 4X more successful for white women with lots of vitamin D – Oct 2012
- Assisted Reproduction might be aided by Vitamin D – review Dec 2014
- Vitamin D somewhat assists reproduction – both the mother and the father – May 2014
- Vitamin D and aspects of female fertility (especially PCOS) – May 2017
- Fertility and Sperm category listing has
65 items along with related searches
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.
- Bouillon, R, Carmeliet, G, Daci, E, Segaert, S, Verstuyf, A (1998) Vitamin D metabolism and action. Osteoporos Int 8: pp. S13-S19 CrossRef
- 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
- 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
- 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
- Forrest, KYZ, Stuhldreher, WL (2011) Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res 31: pp. 48-54 CrossRef
- 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
- 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
- Dietary reference intakes for calcium and vitamin D. National Academy Press, Washington, DC
- Vitamin D: screening and supplementation during pregnancy. Committee opinion no. 495. Obstet Gynecol 118: pp. 197-198 CrossRef
- Kwiecinski, GG, Petrie, GI, Deluca, HF (1989) Vitamin D is necessary for reproductive functions of the male rat. J Nutr 119: pp. 741-744
- 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
- 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
- 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
- Corbett, ST, Hill, O, Nangia, AK (2006) Vitamin D receptor found in human sperm. Urology 68: pp. 1345-1349 CrossRef
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Lebovic, DI, Mueller, MD, Taylor, RN (2001) Immunobiology of endometriosis. Fertil Steril 75: pp. 1-10 CrossRef
- 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
- 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
- Goodarzi, MO, Dumesic, DA, Chazenbalk, G, Azziz, R (2011) Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 7: pp. 219-231 CrossRef
- 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
- 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
- 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
- Tai, K, Need, AG, Horowitz, M, Chapman, IM (2008) Vitamin D, glucose, insulin, and insulin sensitivity. Nutrition 24: pp. 279-285 CrossRef
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Merhi, Z (2014) Advanced glycation end products and their relevance in female reproduction. Hum Reprod 29: pp. 135-145 CrossRef
- Singh, R, Barden, A, Mori, T, Beilin, L (2001) Advanced glycation end-products: a review. Diabetologia 44: pp. 129-146 CrossRef
- 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
- Unoki, H, Yamagishi, S (2008) Advanced glycation end products and insulin resistance. Curr Pharm Des 14: pp. 987-989 CrossRef
- 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
- 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
- Jia, X, Chang, T, Wilson, TW, Wu, L (2012) Methylglyoxal mediates adipocyte proliferation by increasing phosphorylation of Akt1. PLoS One 7: pp. e36610 CrossRef
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
- Consumer price index. Bureau of Labor Statistics, Washington, DC
- 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.
- Drug Price Search. https://www.rxpricequotes.com. Accessed 11 Aug 2014.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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.
1094 visitors, last modified 14 May, 2017, URL: