Journal of Assisted Reproduction and Genetics

, Volume 19, Issue 4, pp 164–168 | Cite as

Ascorbic Acid Supplement During Luteal Phase in IVF

  • Georg Griesinger
  • Katharina Franke
  • Cordelia Kinast
  • Alexandra Kutzelnigg
  • Sandra Riedinger
  • Sandor Kulin
  • Steven G. Kaali
  • Wilfried Feichtinger


Purpose: To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospective, randomized, placebo-controlled, group comparative, double-blind study. Methods: Voluntary daily oral intake of either ascorbic acid (1, 5, or 10 g/day) or Placebo for 14 days after follicle aspiration for IVF-ET procedure. Data was obtained on 620 cases of women, age <40 years, undergoing first IVF-embryo transfer cycles in two private out-patient infertility clinics. All women were stimulated by the same protocol. The mean age was 31.73 (±4.4 SD) years. Results: No differences in clinical pregnancy rate and implantation rate were noted in statistical logistic regression analysis between the four intake groups. Conclusions: There was no clinical evidence of any beneficial effect, as defined by main outcome measures, of ascorbic acid on IVF-ET. Our data suggest there is no obvious value of high dosed intake of vitamin C during luteal phase in infertility treatment.

ascorbic acid fertility IVF luteal phase 


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  1. 1.
    Paeschke KD: The role of ascorbic acid in ovulation. Zentralbl Gynakol 1969;91(35):1129–1132Google Scholar
  2. 2.
    Millar J: Vitamin C–the primate fertility factor? Med Hypotheses 1992;38:292–295Google Scholar
  3. 3.
    Wagner F, Hofmann KD, Preibsch W, Koob G: Ascorbic acid content of the human ovary. Zentralbl Gynakol 1970; 92(33):1060–1061Google Scholar
  4. 4.
    Hoch-Ligeti C, Bourne GH: Changes in the concentration and histological distribution of ascorbic acid in ovaries, adrenals and liver of rats during oestrus cycle. Br J Pathol 1984;29: 400–407Google Scholar
  5. 5.
    Deane HW: Histochemical observation on the ovary and oviduct of the albino rat during the oestrus cycle. Am J Anat 1952;91:363–393Google Scholar
  6. 6.
    Levine M, Morita K: Ascorbic acid in endocrine systems.Vitam Horm 1985;42:1–64Google Scholar
  7. 7.
    Musicki B, Kodaman PH, Aten RF, Behrman HR: Endocrine regulation of ascorbic acid transport and secretion in luteal cells. Biol Reprod 1996;54(2):399–406Google Scholar
  8. 8.
    Paszkowski T, Clarke RN: The Graafian follicle is a site of L-ascorbate accumulation. J Assist Reprod Genet 1999;16(1): 41–45Google Scholar
  9. 9.
    Himeno N, Kawamura N, Okamura H, Mori T, Fukumoto M, Midorikawa O: Collagen synthetic activity in rabbit ovary during ovulation and its blockage by indomethacin. Acta Obstet Gynaecol Jpn 1984;36:1930–1934Google Scholar
  10. 10.
    Luck MR, Zhao Y: Structural remodelling of reproductive tissues. J Endocrinol 1995;146(2):191–195Google Scholar
  11. 11.
    Luck MR, Zhao Y: Identification and measurement of collagen in the bovine corpus luteum and its relationship with ascorbic acid and tissue development. J Reprod Fertil 1993;99(2):647–652Google Scholar
  12. 12.
    Kramer MM, Harman MT, Brill AK: Disturbances of reproduction and ovarian changes in the guinea-pig in relation to vitamin C deficiency. Am J Physiol 1933;106:611–622Google Scholar
  13. 13.
    Eipper BA, Mains RE:The role of ascorbate in the biosynthesis of neuroendocrine peptides. Am J Clin Nutr 1991;54: 1153S–1156SGoogle Scholar
  14. 14.
    Goralczyk R, Moser UK, Matter U, Weiser H: Regulation of steroid hormone metabolism requires L-ascorbic acid.Ann NY Acad Sci 1992;669:349–351Google Scholar
  15. 15.
    Luck MR, Jungclas B: The time-course of oxytocin secretion from cultured bovine granulosa cells, stimulated by ascorbate and catecholamines. J Endocrinol 1988;116(2): 247–258Google Scholar
  16. 16.
    Guarnaccia MM, Takami M, Jones EE, Preston SL, Behrman HR: Luteinizing hormone depletes ascorbic acid in preovulatory follicles. Fertil Steril 2000;74(5):959–963Google Scholar
  17. 17.
    Aten RF, Duarte KM, Behrman HR: Regulation of ovarian antioxidant vitamins, reduced gluthatione, and lipid peroxidation by luteinizing hormone and prostaglandin F. Biol Reprod 1992;46:401–407Google Scholar
  18. 18.
    Behrman HR, Preston SL: Luteolytic actions of peroxide in rat ovarian cells. Endocrinology 1989;124:2895–2900Google Scholar
  19. 19.
    Margolin Y, Aten RF, Behrman HR: Antigonadotropic and antisteroidogenic actions of peroxide in rat granulosa cells. Endocrinology 1990;127:245–250Google Scholar
  20. 20.
    Buettner GR: The pecking order of free radicals and antioxidants: Lipid peroxidation, α-tocopherol, and ascorbate. Arch Biochem Biophys 1993;300:535–543Google Scholar
  21. 21.
    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: 261–263Google Scholar
  22. 22.
    Tilly JL, Tilly KI: Inhibitors of oxidative stress mimic the ability of follicle stimulating hormone to suppress apoptosis in cultured rat ovarian follicles. Endocrinology 1995;136: 242–252Google Scholar
  23. 23.
    Kololdecik TR, Aten RF, Behrman HR: Ascorbic aciddependent cytoprotection of ovarian cells by leukocyte and nonleukocyte peroxidases. Biochem Pharmacol 1998;55(9): 1497–1503Google Scholar
  24. 24.
    Qanungo S, Mukherjea M: Ontogenic profile of some antioxidants and lipid peroxidation in human placental and fetal tissues. Mol Cell Biochem 2000;215(1/2):11–19Google Scholar
  25. 25.
    Wilson CW: Letter: Vitamin C and fertility. Lancet 1973; 2(7833):859–860Google Scholar
  26. 26.
    Luck MR, Jeyaseelan I, Schoels RA: Ascorbic acid and fertility. Biol Reprod 1995;52:262–266Google Scholar
  27. 27.
    Igarashi M: Augmentative effect of ascorbic acid upon induction of human ovulation in clomiphene-ineffective anovulatory women. Int J Fertil 1977;22(3):168–173Google Scholar
  28. 28.
    Phillips PH, Lardy HA, Boyer PD, Werner GM: The relationship of ascorbic acid to reproduction in the cow. J Dairy Sci 1941;24:153–158Google Scholar
  29. 29.
    Guerin P, Mouatassim SE, Menezo Y: Oxidative stress and protection against reactive oxygen species in the pre implantation embryo and its surroundings. Hum Reprod 2001;7(2): 175–189Google Scholar
  30. 30.
    Chatterjee IB: Evolution and the biosynthesis of ascorbic acid. Science 1973;182:1271–1272Google Scholar
  31. 31.
    Kemeter P, Feichtinger W: Experience with a new fixed stimulation protocoll without hormone determinations for programmed oocyte retrieval for in vitro fertilization. Hum Reprod 1989;4:53–58Google Scholar
  32. 32.
    Vural P, Akgul C, Yildirim A, Canbaz M: Antioxidant defence in recurrent abortion. Clin Chim Acta 2000;295(1/2):169–177Google Scholar
  33. 33.
    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):261–263Google Scholar
  34. 34.
    Miesel R, Drzejczak PJ, Kurpisz M: Oxidative stress during the interaction of gametes. Biol Reprod 1993;49:918–923Google Scholar
  35. 35.
    Yamashita T, Yamazaki H, Kon Y: Progressive effect of alphaphenyl-N-tert-butyl nitrone (PBN) on rat embryo development in vitro: Free Radic Biol Med 1997;23:1073–1077Google Scholar
  36. 36.
    Pauling L: Vitamin C and the Common Cold. San Francisco, WH Freeman, 1976Google Scholar
  37. 37.
    Pauling L: Vitamin C, the Common Cold and the Flu. San Francisco, WH Freeman, 1976Google Scholar
  38. 38.
    Pauling L: How to Live Longer and Feel Better. New York, WH Freeman, 1986Google Scholar
  39. 39.
    Kallner A, Hartmann D, Hornig D: Steady-state turnover and body pool of ascorbic acid in man. Am J Clin Nutr 1979;32: 530–539Google Scholar
  40. 40.
    Bendich A, Langseth L: The health effects of vitamin C supplementation: A review. J Am Coll Nutr 1995;14(2):124–136Google Scholar
  41. 41.
    Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR: Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc Natl Acad Sci USA 1996;93(8):3704–3709Google Scholar
  42. 42.
    Grimble RF: Effect of antioxidative vitamins on immune function with clinical applications. Int J Vitam Nutr Res 1997;67(5):312–320Google Scholar
  43. 43.
    Crary EJ, McCarty MF: Potential clinical applications for highdose nutritional antioxidants. Med Hypotheses 1984;13(1):77–98Google Scholar
  44. 44.
    Franchin R, Harmas A, Benaoudie F, Lundkvist U, Oliviennes F, Frydman R: Microbial flora of the cervix assessed at the time of embryo transfer adversely affects in vitro fertilization outcome. Fertil Steril 1998;70(5):866–876Google Scholar
  45. 45.
    Murray AA, Molinek MD, Baker SJ, Kojiman FN, Smith MF, Hillier SG, Spears N: Role of ascorbic acid in promoting follicle integrity and survival in intact mouse ovarian follicles in vitro. Reproduction 2001;121(1):89–96Google Scholar

Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Georg Griesinger
    • 1
    • 2
  • Katharina Franke
    • 2
  • Cordelia Kinast
    • 2
  • Alexandra Kutzelnigg
    • 2
  • Sandra Riedinger
    • 2
  • Sandor Kulin
    • 3
  • Steven G. Kaali
    • 3
  • Wilfried Feichtinger
    • 2
  1. 1.Department of Obstetrics and GynecologyUniversity of ViennaViennaAustria
  2. 2.Institut fuer SterilitaetsbetreuungViennaAustria
  3. 3.Kaali IntezetBudapestHungary

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