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Are Dietary Supplements Beneficial for IVF Patients?

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Biennial Review of Infertility

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Abstract

The use of assisted reproductive technologies including in vitro fertilization is increasing globally, and modifiable factors that can improve success rates would have enormous public health significance. We review the literature on the effect of dietary supplementation on IVF outcomes including pregnancy and live birth. The main dietary factors for which there is some evidence of a relationship with these outcomes are folic acid, phytoestrogens, antioxidants, and vitamin D. Although several studies report a significant association between dietary supplementation and improved IVF outcomes, the number of large, high-quality, well-controlled, and randomized trials is limited. As a result, current evidence is not supportive of a change in practice towards routine recommendation of specific dietary supplements for the purpose of improving IVF outcomes. However, given the strength and consistency of the association between folic acid supplementation and IVF outcomes, it would be ideal if this relation were further evaluated in a large randomized controlled trial.

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References

  1. Thoma ME, McLain AC, Louis JF, King RB, Trumble AC, Sundaram R, Buck Louis GM. Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. Fertil Steril. 2013;99(5):1324–31. 5.

    Article  PubMed  PubMed Central  Google Scholar 

  2. CDC. 2010 Assisted reproductive technology fertility clinic success rates report. Atlanta, GA: US Department of Health and Human Services; 2012.

    Google Scholar 

  3. Centers for Disease Control and Prevention, American Society for Reproductive Medicine, Society for Assisted Reproductive Technology. 2012 Assisted reproductive technology fertility clinic success rates report. Atlanta, GA: US Department of Health and Human Services; 2014.

    Google Scholar 

  4. Matthews TJ, Hamilton BE. Delayed childbearing: more women are having their first child later in life. NCHS Data Brief. 2009;August(21):1–8.

    Google Scholar 

  5. van Loendersloot LL, van Wely M, Limpens J, Bossuyt PM, Repping S, van der Veen F. Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update. 2010;16(6):577–89.

    Article  PubMed  Google Scholar 

  6. Verhaak CM, Smeenk JM, Nahuis MJ, Kremer JA, Braat DD. Long-term psychological adjustment to IVF/ICSI treatment in women. Hum Reprod. 2007;22(1):305–8.

    Article  CAS  PubMed  Google Scholar 

  7. Smith JF, Eisenberg ML, Millstein SG, Nachtigall RD, Shindel AW, Wing H, Cedars M, Pasch L, Katz PP, Infertility Outcomes Program Project G. The use of complementary and alternative fertility treatment in couples seeking fertility care: data from a prospective cohort in the United States. Fertil Steril. 2010;93(7):2169–74.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dietary Supplement Health and Education Act of 1994, United States Congress, 103rd Session. 1994.

    Google Scholar 

  9. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991;338(8760):131–7.

    Article  Google Scholar 

  10. Force USPST. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009;150(9):626–31.

    Article  Google Scholar 

  11. World Health Organization, United Nations Children’s Fund, International Council for the Control of Iodine Deficiency Disorders. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 3rd ed. Geneva, Switzerland: World Health Organization; 2007.

    Google Scholar 

  12. Rogers LK, Valentine CJ, Keim SA. DHA supplementation: current implications in pregnancy and childhood. Pharmacol Res. 2013;70(1):13–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Forges T, Monnier-Barbarino P, Alberto JM, Gueant-Rodriguez RM, Daval JL, Gueant JL. Impact of folate and homocysteine metabolism on human reproductive health. Hum Reprod Update. 2007;13(3):225–38.

    Article  CAS  PubMed  Google Scholar 

  14. Mills JL, Scott JM, Kirke PN, McPartlin JM, Conley MR, Weir DG, Molloy AM, Lee YJ. Homocysteine and neural tube defects. J Nutr. 1996;126(3):756S–60.

    CAS  PubMed  Google Scholar 

  15. Nelen WL, Blom HJ, Steegers EA, den Heijer M, Eskes TK. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril. 2000;74(6):1196–9.

    Article  CAS  PubMed  Google Scholar 

  16. Steegers-Theunissen RP, Van Iersel CA, Peer PG, Nelen WL, Steegers EA. Hyperhomocysteinemia, pregnancy complications, and the timing of investigation. Obstet Gynecol. 2004;104(2):336–43.

    Article  CAS  PubMed  Google Scholar 

  17. Centers for Disease Control and Prevention. Folic acid recommendations. Atlanta, GA. 2012. http://www.cdc.gov/ncbddd/folicacid/recommendations.html. Cited 21 September 2014.

  18. Wolff T, Witkop CT, Miller T, Syed SB. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. preventive services task force. Rockville, MD; Agency for Healthcare Research and Quality (US). 2009.

    Google Scholar 

  19. Berry RJ, Bailey L, Mulinare J, Bower C, Folic Acid Working G. Fortification of flour with folic acid. Food Nutr Bull. 2010;31(1 Suppl):S22–35.

    PubMed  Google Scholar 

  20. Willmott M, Bartosik DB, Romanoff EB. The effect of folic acid on superovulation in the immature rat. J Endocrinol. 1968;41(3):439–45.

    Article  CAS  PubMed  Google Scholar 

  21. Matte JJ, Girard CL, Brisson GJ. Folic acid and reproductive performances of sows. J Anim Sci. 1984;59(4):1020–5.

    CAS  PubMed  Google Scholar 

  22. O’Neill C. Endogenous folic acid is essential for normal development of preimplantation embryos. Hum Reprod. 1998;13(5):1312–6.

    Article  PubMed  Google Scholar 

  23. Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Use of multivitamins, intake of B vitamins, and risk of ovulatory infertility. Fertil Steril. 2008;89(3):668–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Gaskins AJ, Mumford SL, Chavarro JE, Zhang C, Pollack AZ, Wactawski-Wende J, Perkins NJ, Schisterman EF. The impact of dietary folate intake on reproductive function in premenopausal women: a prospective cohort study. PLoS One. 2012;7(9):e46276.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Thaler CJ, Budiman H, Ruebsamen H, Nagel D, Lohse P. Effects of the common 677C>T mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness to recombinant follicle-stimulating hormone. Am J Reprod Immunol. 2006;55(4):251–8.

    Article  CAS  PubMed  Google Scholar 

  26. Hecht S, Pavlik R, Lohse P, Noss U, Friese K, Thaler CJ. Common 677C–>T mutation of the 5,10-methylenetetrahydrofolate reductase gene affects follicular estradiol synthesis. Fertil Steril. 2009;91(1):56–61.

    Article  CAS  PubMed  Google Scholar 

  27. Pavlik R, Hecht S, Ochsenkuhn R, Noss U, Lohse P, Thaler CJ. Divergent effects of the 677C>T mutation of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene on ovarian responsiveness and anti-Mullerian hormone concentrations. Fertil Steril. 2011;95(7):2257–62.

    Article  CAS  PubMed  Google Scholar 

  28. Boxmeer JC, Macklon NS, Lindemans J, Beckers NG, Eijkemans MJ, Laven JS, Steegers EA, Steegers-Theunissen RP. IVF outcomes are associated with biomarkers of the homocysteine pathway in monofollicular fluid. Hum Reprod. 2009;24(5):1059–66.

    Article  CAS  PubMed  Google Scholar 

  29. Ebisch IM, Peters WH, Thomas CM, Wetzels AM, Peer PG, Steegers-Theunissen RP. Homocysteine, glutathione and related thiols affect fertility parameters in the (sub)fertile couple. Hum Reprod. 2006;21(7):1725–33.

    Article  CAS  PubMed  Google Scholar 

  30. Laanpere M, Altmae S, Kaart T, Stavreus-Evers A, Nilsson TK, Salumets A. Folate-metabolizing gene variants and pregnancy outcome of IVF. Reprod Biomed Online. 2011;22(6):603–14.

    Article  CAS  PubMed  Google Scholar 

  31. Gaskins AJ, Afeiche MC, Wright DL, Toth TL, Williams PL, Gillman MW, Hauser R, Chavarro JE. Dietary folate and reproductive success among women undergoing assisted reproduction. Obstet Gynecol. 2014;124(4):801–9.

    Article  CAS  PubMed  Google Scholar 

  32. Murto T, Skoog Svanberg A, Yngve A, Nilsson TK, Altmae S, Wanggren K, Salumets A, Stavreus-Evers A. Folic acid supplementation and IVF pregnancy outcome in women with unexplained infertility. Reprod Biomed Online. 2014;28(6):766–72.

    Article  CAS  PubMed  Google Scholar 

  33. Haggarty P, McCallum H, McBain H, Andrews K, Duthie S, McNeill G, Templeton A, Haites N, Campbell D, Bhattacharya S. Effect of B vitamins and genetics on success of in-vitro fertilisation: prospective cohort study. Lancet. 2006;367(9521):1513–9.

    Article  CAS  PubMed  Google Scholar 

  34. Gaskins AJ, Rich-Edwards JW, Hauser R, Williams PL, Gillman MW, Ginsburg ES, Missmer SA, Chavarro JE. Maternal prepregnancy folate intake and risk of spontaneous abortion and stillbirth. Obstet Gynecol. 2014;124(1):23–31.

    Article  CAS  PubMed  Google Scholar 

  35. Pritts EA, Atwood AK. Luteal phase support in infertility treatment: a meta-analysis of the randomized trials. Hum Reprod. 2002;17(9):2287–99.

    Article  CAS  PubMed  Google Scholar 

  36. Baird DD, Wilcox AJ, Weinberg CR, Kamel F, McConnaughey DR, Musey PI, Collins DC. Preimplantation hormonal differences between the conception and non-conception menstrual cycles of 32 normal women. Hum Reprod. 1997;12(12):2607–13.

    Article  CAS  PubMed  Google Scholar 

  37. Lipson SF, Ellison PT. Comparison of salivary steroid profiles in naturally occurring conception and non-conception cycles. Hum Reprod. 1996;11(10):2090–6.

    Article  CAS  PubMed  Google Scholar 

  38. Stewart DR, Overstreet JW, Nakajima ST, Lasley BL. Enhanced ovarian steroid secretion before implantation in early human pregnancy. J Clin Endocrinol Metab. 1993;76(6):1470–6.

    CAS  PubMed  Google Scholar 

  39. Younis JS, Simon A, Laufer N. Endometrial preparation: lessons from oocyte donation. Fertil Steril. 1996;66(6):873–84.

    CAS  PubMed  Google Scholar 

  40. Hutchinson-Williams KA, Lunenfeld B, Diamond MP, Lavy G, Boyers SP, DeCherney AH. Human chorionic gonadotropin, estradiol, and progesterone profiles in conception and nonconception cycles in an in vitro fertilization program. Fertil Steril. 1989;52(3):441–5.

    CAS  PubMed  Google Scholar 

  41. Emperaire JC, Ruffie A, Audebert AJ, Verdaguer S. Early prognosis for IVF pregnancies through plasma oestrogens. Lancet. 1984;2(8412):1151.

    Article  CAS  PubMed  Google Scholar 

  42. Laufer N, Navot D, Schenker JG. The pattern of luteal phase plasma progesterone and estradiol in fertile cycles. Am J Obstet Gynecol. 1982;143(7):808–13.

    CAS  PubMed  Google Scholar 

  43. Unfer V, Casini ML, Gerli S, Costabile L, Mignosa M, Di Renzo GC. Phytoestrogens may improve the pregnancy rate in in vitro fertilization-embryo transfer cycles: a prospective, controlled, randomized trial. Fertil Steril. 2004;82(6):1509–13.

    Article  CAS  PubMed  Google Scholar 

  44. Shahin AY, Ismail AM, Zahran KM, Makhlouf AM. Adding phytoestrogens to clomiphene induction in unexplained infertility patients—a randomized trial. Reprod Biomed Online. 2008;16(4):580–8.

    Article  CAS  PubMed  Google Scholar 

  45. Eden JA, Place J, Carter GD, Jones J, Alaghband-Zadeh J, Pawson ME. The effect of clomiphene citrate on follicular phase increase in endometrial thickness and uterine volume. Obstet Gynecol. 1989;73(2):187–90.

    CAS  PubMed  Google Scholar 

  46. Nakamura Y, Ono M, Yoshida Y, Sugino N, Ueda K, Kato H. Effects of clomiphene citrate on the endometrial thickness and echogenic pattern of the endometrium. Fertil Steril. 1997;67(2):256–60.

    Article  CAS  PubMed  Google Scholar 

  47. Yagel S, Ben-Chetrit A, Anteby E, Zacut D, Hochner-Celnikier D, Ron M. The effect of ethinyl estradiol on endometrial thickness and uterine volume during ovulation induction by clomiphene citrate. Fertil Steril. 1992;57(1):33–6.

    CAS  PubMed  Google Scholar 

  48. Ruder EH, Hartman TJ, Blumberg J, Goldman MB. Oxidative stress and antioxidants: exposure and impact on female fertility. Hum Reprod Update. 2008;14(4):345–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Gupta S, Agarwal A, Banerjee J, Alvarez JG. The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review. Obstet Gynecol Surv. 2007;62(5):335–47. quiz 53–4.

    Article  PubMed  Google Scholar 

  50. Polak G, Koziol-Montewka M, Gogacz M, Blaszkowska I, Kotarski J. Total antioxidant status of peritoneal fluid in infertile women. Eur J Obstet Gynecol Reprod Biol. 2001;94(2):261–3.

    Article  CAS  PubMed  Google Scholar 

  51. Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril. 2003;80(1):123–7.

    Article  PubMed  Google Scholar 

  52. Brown LA, Kerr CJ, Whiting P, Finer N, McEneny J, Ashton T. Oxidant stress in healthy normal-weight, overweight, and obese individuals. Obesity (Silver Spring). 2009;17(3):460–6.

    Article  CAS  Google Scholar 

  53. Tatone C, Amicarelli F, Carbone MC, Monteleone P, Caserta D, Marci R, Artini PG, Piomboni P, Focarelli R. Cellular and molecular aspects of ovarian follicle ageing. Hum Reprod Update. 2008;14(2):131–42.

    Article  CAS  PubMed  Google Scholar 

  54. Showell MG, Brown J, Clarke J, Hart RJ. Antioxidants for female subfertility. Cochrane Database Syst Rev. 2013;8, CD007807.

    PubMed  Google Scholar 

  55. Battaglia C, Salvatori M, Maxia N, Petraglia F, Facchinetti F, Volpe A. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients. Hum Reprod. 1999;14(7):1690–7.

    Article  CAS  PubMed  Google Scholar 

  56. Ruder EH, Hartman TJ, Reindollar RH, Goldman MB. Female dietary antioxidant intake and time to pregnancy among couples treated for unexplained infertility. Fertil Steril. 2014;101(3):759–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Hewison M. Vitamin D, and immune function: an overview. Proc Nutr Soc. 2012;71(1):50–61.

    Article  CAS  PubMed  Google Scholar 

  58. Yoshizawa T, Handa Y, Uematsu Y, Takeda S, Sekine K, Yoshihara Y, Kawakami T, Arioka K, Sato H, Uchiyama Y, Masushige S, Fukamizu A, Matsumoto T, Kato S. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat Genet. 1997;16(4):391–6.

    Article  CAS  PubMed  Google Scholar 

  59. 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):1317–24.

    CAS  PubMed  Google Scholar 

  60. Halloran BP, DeLuca HF. Effect of vitamin D deficiency on fertility and reproductive capacity in the female rat. J Nutr. 1980;110(8):1573–80.

    CAS  PubMed  Google Scholar 

  61. Parikh G, Varadinova M, Suwandhi P, Araki T, Rosenwaks Z, Poretsky L, Seto-Young D. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm Metab Res. 2010;42(10):754–7.

    Article  CAS  PubMed  Google Scholar 

  62. Avila E, Diaz L, Halhali A, Larrea F. Regulation of 25-hydroxyvitamin D3 1alpha-hydroxylase, 1,25-dihydroxyvitamin D3 24-hydroxylase and vitamin D receptor gene expression by 8-bromo cyclic AMP in cultured human syncytiotrophoblast cells. J Steroid Biochem Mol Biol. 2004;89–90(1–5):115–9.

    Article  PubMed  Google Scholar 

  63. Evans KN, Nguyen L, Chan J, Innes BA, Bulmer JN, Kilby MD, Hewison M. Effects of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on cytokine production by human decidual cells. Biol Reprod. 2006;75(6):816–22.

    Article  CAS  PubMed  Google Scholar 

  64. Rojansky N, Benshushan A, Meirsdorf S, Lewin A, Laufer N, Safran A. Seasonal variability in fertilization and embryo quality rates in women undergoing IVF. Fertil Steril. 2000;74(3):476–81.

    Article  CAS  PubMed  Google Scholar 

  65. Rojansky N, Brzezinski A, Schenker JG. Seasonality in human reproduction: an update. Hum Reprod. 1992;7(6):735–45.

    CAS  PubMed  Google Scholar 

  66. 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):3321–7.

    Article  CAS  PubMed  Google Scholar 

  67. Ozkan S, Jindal S, Greenseid K, Shu J, Zeitlian G, Hickmon C, Pal L. Replete vitamin D stores predict reproductive success following in vitro fertilization. Fertil Steril. 2010;94(4):1314–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. 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):E77–82.

    Article  PubMed  PubMed Central  Google Scholar 

  69. 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.

    Article  CAS  PubMed  Google Scholar 

  70. 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.

    Article  CAS  PubMed  Google Scholar 

  71. Aleyasin A, Hosseini MA, Mahdavi A, Safdarian L, Fallahi P, Mohajeri MR, Abbasi M, Esfahani F. 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.

    Article  CAS  PubMed  Google Scholar 

  72. Anifandis GM, Dafopoulos K, Messini CI, Chalvatzas N, Liakos N, Pournaras S, Messinis IE. Prognostic value of follicular fluid 25-OH vitamin D and glucose levels in the IVF outcome. Reprod Biol Endocrinol. 2010;8:91.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr. 2008;88(6):1519–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Boston University School of Public Health, Boston, MA, USA

    Amelia Wesselink MPH

  2. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    Jorge E. Chavarro MD, ScD

  3. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Jorge E. Chavarro MD, ScD

  4. Department of Obstetrics and Gynecology, Boston Medical Center, Boston University, Boston, MA, USA

    Shruthi Mahalingaiah MD

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  1. Jorge E. Chavarro MD, ScD
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Correspondence to Shruthi Mahalingaiah MD .

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Editors and Affiliations

  1. Professor, Departments of Surgery (Urology), Obstetrics and Gynecology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah, USA

    Douglas T. Carrell

  2. James J. Colt Professor of Urology, Chairman, Department of Urology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York, USA

    Peter N. Schlegel

  3. Professor, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA

    Catherine Racowsky

  4. Scientific Director, Reproductive Medicine Unit, S.I.S.M.E.R. s.r.l., Day Surgery Clinic della Riproduzione (SISMeR), Bologna, Bologna, Italy

    Luca Gianaroli

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Wesselink, A., Chavarro, J.E., Mahalingaiah, S. (2015). Are Dietary Supplements Beneficial for IVF Patients?. In: Carrell, D., Schlegel, P., Racowsky, C., Gianaroli, L. (eds) Biennial Review of Infertility. Springer, Cham. https://doi.org/10.1007/978-3-319-17849-3_16

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