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. 2002 Apr;19(4):164–168. doi: 10.1023/A:1014837811353

Ascorbic Acid Supplement During Luteal Phase in IVF

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,✉
PMCID: PMC3455656  PMID: 12036083

Abstract

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.

Keywords: ascorbic acid, fertility, IVF, luteal phase

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REFERENCES

  • 1.Paeschke KD. The role of ascorbic acid in ovulation. Zentralbl Gynakol. 1969;91(35):1129–1132. [PubMed] [Google Scholar]
  • 2.Millar J. Vitamin C–the primate fertility factor? Med Hypotheses. 1992;38:292–295. doi: 10.1016/0306-9877(92)90019-9. [DOI] [PubMed] [Google Scholar]
  • 3.Wagner F, Hofmann KD, Preibsch W, Koob G. Ascorbic acid content of the human ovary. Zentralbl Gynakol. 1970;92(33):1060–1061. [PubMed] [Google Scholar]
  • 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;29:400–407. [PMC free article] [PubMed] [Google Scholar]
  • 5.Deane HW. Histochemical observation on the ovary and oviduct of the albino rat during the oestrus cycle. Am J Anat. 1952;91:363–393. doi: 10.1002/aja.1000910303. [DOI] [PubMed] [Google Scholar]
  • 6.Levine M, Morita K. Ascorbic acid in endocrine systems. Vitam Horm. 1985;42:1–64. doi: 10.1016/s0083-6729(08)60060-6. [DOI] [PubMed] [Google Scholar]
  • 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):399–406. doi: 10.1095/biolreprod54.2.399. [DOI] [PubMed] [Google Scholar]
  • 8.Paszkowski T, Clarke RN. The Graafian follicle is a site of L-ascorbate accumulation. J Assist Reprod Genet. 1999;16(1):41–45. doi: 10.1023/A:1022597629622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 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;36:1930–1934. [PubMed] [Google Scholar]
  • 10.Luck MR, Zhao Y. Structural remodelling of reproductive tissues. J Endocrinol. 1995;146(2):191–195. doi: 10.1677/joe.0.1460191. [DOI] [PubMed] [Google Scholar]
  • 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):647–652. doi: 10.1530/jrf.0.0990647. [DOI] [PubMed] [Google Scholar]
  • 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;106:611–622. [Google Scholar]
  • 13.Eipper BA, Mains RE. The role of ascorbate in the biosynthesis of neuroendocrine peptides. Am J Clin Nutr. 1991;54:1153S–1156S. doi: 10.1093/ajcn/54.6.1153s. [DOI] [PubMed] [Google Scholar]
  • 14.Goralczyk R, Moser UK, Matter U, Weiser H. Regulation of steroid hormone metabolism requires L-ascorbic acid. Ann NY Acad Sci. 1992;669:349–351. doi: 10.1111/j.1749-6632.1992.tb17120.x. [DOI] [PubMed] [Google Scholar]
  • 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):247–258. doi: 10.1677/joe.0.1160247. [DOI] [PubMed] [Google Scholar]
  • 16.Guarnaccia MM, Takami M, Jones EE, Preston SL, Behrman HR. Luteinizing hormone depletes ascorbic acid in preovulatory follicles. Fertil Steril. 2000;74(5):959–963. doi: 10.1016/s0015-0282(00)01550-8. [DOI] [PubMed] [Google Scholar]
  • 17.Aten RF, Duarte KM, Behrman HR. Regulation of ovarian antioxidant vitamins, reduced gluthatione, and lipid peroxidation by luteinizing hormone and prostaglandin F2α. Biol Reprod. 1992;46:401–407. doi: 10.1095/biolreprod46.3.401. [DOI] [PubMed] [Google Scholar]
  • 18.Behrman HR, Preston SL. Luteolytic actions of peroxide in rat ovarian cells. Endocrinology. 1989;124:2895–2900. doi: 10.1210/endo-124-6-2895. [DOI] [PubMed] [Google Scholar]
  • 19.Margolin Y, Aten RF, Behrman HR. Antigonadotropic and antisteroidogenic actions of peroxide in rat granulosa cells. Endocrinology. 1990;127:245–250. doi: 10.1210/endo-127-1-245. [DOI] [PubMed] [Google Scholar]
  • 20.Buettner GR. The pecking order of free radicals and antioxidants: Lipid peroxidation, α-tocopherol, and ascorbate. Arch Biochem Biophys. 1993;300:535–543. doi: 10.1006/abbi.1993.1074. [DOI] [PubMed] [Google Scholar]
  • 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;94:261–263. doi: 10.1016/s0301-2115(00)00352-3. [DOI] [PubMed] [Google Scholar]
  • 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;136:242–252. doi: 10.1210/endo.136.1.7828537. [DOI] [PubMed] [Google Scholar]
  • 23.Kololdecik TR, Aten RF, Behrman HR. Ascorbic aciddependent cytoprotection of ovarian cells by leukocyte and nonleukocyte peroxidases. Biochem Pharmacol. 1998;55(9):1497–1503. doi: 10.1016/s0006-2952(97)00668-0. [DOI] [PubMed] [Google Scholar]
  • 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):11–19. doi: 10.1023/a:1026511420505. [DOI] [PubMed] [Google Scholar]
  • 25.Wilson CW. Letter: Vitamin C and fertility. Lancet. 1973;2(7833):859–860. doi: 10.1016/s0140-6736(73)90919-7. [DOI] [PubMed] [Google Scholar]
  • 26.Luck MR, Jeyaseelan I, Schoels RA. Ascorbic acid and fertility. Biol Reprod. 1995;52:262–266. doi: 10.1095/biolreprod52.2.262. [DOI] [PubMed] [Google Scholar]
  • 27.Igarashi M. Augmentative effect of ascorbic acid upon induction of human ovulation in clomiphene-ineffective anovulatory women. Int J Fertil. 1977;22(3):168–173. [PubMed] [Google Scholar]
  • 28.Phillips PH, Lardy HA, Boyer PD, Werner GM. The relationship of ascorbic acid to reproduction in the cow. J Dairy Sci. 1941;24:153–158. [Google Scholar]
  • 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):175–189. doi: 10.1093/humupd/7.2.175. [DOI] [PubMed] [Google Scholar]
  • 30.Chatterjee IB. Evolution and the biosynthesis of ascorbic acid. Science. 1973;182:1271–1272. doi: 10.1126/science.182.4118.1271. [DOI] [PubMed] [Google Scholar]
  • 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;4:53–58. doi: 10.1093/humrep/4.suppl_1.53. [DOI] [PubMed] [Google Scholar]
  • 32.Vural P, Akgul C, Yildirim A, Canbaz M. Antioxidant defence in recurrent abortion. Clin Chim Acta. 2000;295(1/2):169–177. doi: 10.1016/s0009-8981(99)00255-7. [DOI] [PubMed] [Google Scholar]
  • 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):261–263. doi: 10.1016/s0301-2115(00)00352-3. [DOI] [PubMed] [Google Scholar]
  • 34.Miesel R, Drzejczak PJ, Kurpisz M. Oxidative stress during the interaction of gametes. Biol Reprod. 1993;49:918–923. doi: 10.1095/biolreprod49.5.918. [DOI] [PubMed] [Google Scholar]
  • 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;23:1073–1077. doi: 10.1016/s0891-5849(97)00139-1. [DOI] [PubMed] [Google Scholar]
  • 36.Pauling L. Vitamin C and the Common Cold. San Francisco: WH Freeman; 1976. [Google Scholar]
  • 37.Pauling L. Vitamin C, the Common Cold and the Flu. San Francisco: WH Freeman; 1976. [Google Scholar]
  • 38.Pauling L. How to Live Longer and Feel Better. New York: WH Freeman; 1986. [Google Scholar]
  • 39.Kallner A, Hartmann D, Hornig D. Steady-state turnover and body pool of ascorbic acid in man. Am J Clin Nutr. 1979;32:530–539. doi: 10.1093/ajcn/32.3.530. [DOI] [PubMed] [Google Scholar]
  • 40.Bendich A, Langseth L. The health effects of vitamin C supplementation: A review. J Am Coll Nutr. 1995;14(2):124–136. doi: 10.1080/07315724.1995.10718484. [DOI] [PubMed] [Google Scholar]
  • 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):3704–3709. doi: 10.1073/pnas.93.8.3704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Grimble RF. Effect of antioxidative vitamins on immune function with clinical applications. Int J Vitam Nutr Res. 1997;67(5):312–320. [PubMed] [Google Scholar]
  • 43.Crary EJ, McCarty MF. Potential clinical applications for highdose nutritional antioxidants. Med Hypotheses. 1984;13(1):77–98. doi: 10.1016/0306-9877(84)90132-4. [DOI] [PubMed] [Google Scholar]
  • 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):866–876. doi: 10.1016/s0015-0282(98)00277-5. [DOI] [PubMed] [Google Scholar]
  • 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):89–96. doi: 10.1530/rep.0.1210089. [DOI] [PubMed] [Google Scholar]

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