Advertisement

CONCERN: Does ovary need D-chiro-inositol?

  • Rosalbino IsabellaEmail author
  • Emanuela Raffone
Research

Abstract

Backgroud

Polycystic Ovary Syndrome (PCOS) is a multifactorial pathology that affects 10% of the women in reproductive age being the main cause of infertility due to menstrual dysfunction. Since 1980, it is known that PCOS is associated with insulin resistance (IR). The recognition of this association has prompted extensive investigation on the relationship between insulin and gonadal function, and has turned insulin sensitizer agent as the main therapeutic choice. In particular two different polyalcohol myo-inositol and D-chiro-inositol have been shown to improve insulin resistance, hyperandrogenism and to induce ovulation in PCOS women. In particular, while data on myo-inositol and restored ovulation were consistent, data on D-chiro-inositol were not . Recently, a comparative study, proposed a D-chiro-inositol paradox in the ovary of PCOS patients hypothesizing that only myo-inositol has a specific ovarian action. In the present study we aim to further study the role played by D-chiro-inositol at ovarian level.

Methods

A total of 54 women, aged <40 years and diagnosed with PCOS were enrolled in this study. Patients with insulin resistance and/or hyperglycaemia were excluded from the study. Patients were randomly divided into 5 groups (n=10-12): a placebo group, and 4 groups (A-D) that received 300-600-1200-2400 mg of DCI daily respectively. All treatments were carried out for 8 weeks before follicle stimulating hormone (rFSH) administration.

Results

Total r-FSH units increased significantly in the two groups that received the higher doses of DCI. The number of immature oocytes was significantly increased in the three groups that received the higher doses of DCI. Concurrently, the number of MII oocytes was significantly lower in the D group compared to placebo group. Noteworthy, the number of grade I embryos was significantly reduced by DCI supplementation.

Conclusions

Indeed, increasing DCI dosage progressively worsens oocyte quality and ovarian response.

Keywords

Metformin PCOS Patient Ovarian Response PCOS Woman Oocyte Quality 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Supplementary material

13048_2012_98_MOESM1_ESM.pdf (84 kb)
Authors’ original file for figure 1
13048_2012_98_MOESM2_ESM.pdf (85 kb)
Authors’ original file for figure 2
13048_2012_98_MOESM3_ESM.pdf (35 kb)
Authors’ original file for figure 3

References

  1. 1.
    Taylor AE: Polycystic ovary syndrome. Endocrinol Metab Clin North Am 1998, 27: 877–902. ix 10.1016/S0889-8529(05)70045-1PubMedCrossRefGoogle Scholar
  2. 2.
    Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome Fertil Steril 2004, 81: 19–25.Google Scholar
  3. 3.
    Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS) Hum Reprod 2004, 19: 41–47.Google Scholar
  4. 4.
    Burghen GA, Givens JR, Kitabchi AE: Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980, 50: 113–116. 10.1210/jcem-50-1-113PubMedCrossRefGoogle Scholar
  5. 5.
    Baillargeon JP, Carpentier A: Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity. Fertil Steril 2007, 88: 886–893. 10.1016/j.fertnstert.2006.12.055PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Baptiste CG, Battista MC, Trottier A, Baillargeon JP: Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol 2010, 122: 42–52. 10.1016/j.jsbmb.2009.12.010PubMedCrossRefGoogle Scholar
  7. 7.
    Ehrmann DA: Insulin-lowering therapeutic modalities for polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999, 28: 423–438. viii 10.1016/S0889-8529(05)70078-5PubMedCrossRefGoogle Scholar
  8. 8.
    Hasegawa I, Murakawa H, Suzuki M, Yamamoto Y, Kurabayashi T, Tanaka K: Effect of troglitazone on endocrine and ovulatory performance in women with insulin resistance-related polycystic ovary syndrome. Fertil Steril 1999, 71: 323–327. 10.1016/S0015-0282(98)00454-3PubMedCrossRefGoogle Scholar
  9. 9.
    Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G: Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999, 340: 1314–1320. 10.1056/NEJM199904293401703PubMedCrossRefGoogle Scholar
  10. 10.
    Gerli S, Mignosa M, Di Renzo GC: Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 2003, 7: 151–159.PubMedGoogle Scholar
  11. 11.
    Ng EH, Wat NM, Ho PC: Effects of metformin on ovulation rate, hormonal and metabolic profiles in women with clomiphene-resistant polycystic ovaries: a randomized, double-blinded placebo-controlled trial. Hum Reprod 2001, 16: 1625–1631. 10.1093/humrep/16.8.1625PubMedCrossRefGoogle Scholar
  12. 12.
    Huang LC, Fonteles MC, Houston DB, Zhang C, Larner J: Chiroinositol deficiency and insulin resistance. III. Acute glycogenic and hypoglycemic effects of two inositol phosphoglycan insulin mediators in normal and streptozotocin-diabetic rats in vivo. Endocrinology 1993, 132: 652–657. 10.1210/en.132.2.652PubMedCrossRefGoogle Scholar
  13. 13.
    Papaleo E, Unfer V, Baillargeon JP, De Santis L, Fusi F, Brigante C, Marelli G, Cino I, Redaelli A, Ferrari A: Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol 2007, 23: 700–703. 10.1080/09513590701672405PubMedCrossRefGoogle Scholar
  14. 14.
    Larner J: D-chiro-inositol–its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 2002, 3: 47–60. 10.1080/15604280212528PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ: Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 2002, 17: 1591–1596. 10.1093/humrep/17.6.1591PubMedCrossRefGoogle Scholar
  16. 16.
    Papaleo E, Unfer V, Baillargeon JP, Chiu TT: Contribution of myo-inositol to reproduction. Eur J Obstet Gynecol Reprod Biol 2009, 147: 120–123. 10.1016/j.ejogrb.2009.09.008PubMedCrossRefGoogle Scholar
  17. 17.
    Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, De Santis L: Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 2009, 91: 1750–1754. 10.1016/j.fertnstert.2008.01.088PubMedCrossRefGoogle Scholar
  18. 18.
    Raffone E, Rizzo P, Benedetto V: Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol 2010, 26: 275–280. 10.3109/09513590903366996PubMedCrossRefGoogle Scholar
  19. 19.
    Unfer V, Carlomagno G, Rizzo P, Raffone E, Roseff S: Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Eur Rev Med Pharmacol Sci 2011, 15: 452–457.PubMedGoogle Scholar
  20. 20.
    Borini A, Sciajno R, Bianchi V, Sereni E, Flamigni C, Coticchio G: Clinical outcome of oocyte cryopreservation after slow cooling with a protocol utilizing a high sucrose concentration. Hum Reprod 2006, 21: 512–517.PubMedCrossRefGoogle Scholar
  21. 21.
    Van de Velde H, Nagy ZP, Joris H, De Vos A, Van Steirteghem AC: Effects of different hyaluronidase concentrations and mechanical procedures for cumulus cell removal on the outcome of intracytoplasmic sperm injection. Hum Reprod 1997, 12: 2246–2250. 10.1093/humrep/12.10.2246PubMedCrossRefGoogle Scholar
  22. 22.
    De Santis L, Cino I, Rabellotti E, Papaleo E, Calzi F, Fusi FM, Brigante C, Ferrari A: Oocyte cryopreservation: clinical outcome of slow-cooling protocols differing in sucrose concentration. Reprod Biomed Online 2007, 14: 57–63. 10.1016/S1472-6483(10)60764-XPubMedCrossRefGoogle Scholar
  23. 23.
    Arya BK, Haq AU, Chaudhury K: Oocyte quality reflected by follicular fluid analysis in poly cystic ovary syndrome (PCOS): A hypothesis based on intermediates of energy metabolism. Med Hypotheses 2012, 78: 475–478. 10.1016/j.mehy.2012.01.009PubMedCrossRefGoogle Scholar
  24. 24.
    Ma X, Fan L, Meng Y, Hou Z, Mao YD, Wang W, Ding W, Liu JY: Proteomic analysis of human ovaries from normal and polycystic ovarian syndrome. Mol Hum Reprod 2007, 13: 527–535. 10.1093/molehr/gam036PubMedCrossRefGoogle Scholar
  25. 25.
    Larner J, Craig JW: Urinary myo-inositol-to-chiro-inositol ratios and insulin resistance. Diabetes Care 1996, 19: 76–78.PubMedCrossRefGoogle Scholar
  26. 26.
    Asplin I, Galasko G, Larner J: chiro-inositol deficiency and insulin resistance: a comparison of the chiro-inositol- and the myo-inositol-containing insulin mediators isolated from urine, hemodialysate, and muscle of control and type II diabetic subjects. Proc Natl Acad Sci U S A 1993, 90: 5924–5928. 10.1073/pnas.90.13.5924PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Harwood K, Vuguin P, DiMartino-Nardi J: Current approaches to the diagnosis and treatment of polycystic ovarian syndrome in youth. Horm Res 2007, 68: 209–217.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Matalliotakis I, Kourtis A, Koukoura O, Panidis D: Polycystic ovary syndrome: etiology and pathogenesis. Arch Gynecol Obstet 2006, 274: 187–197. 10.1007/s00404-006-0171-xPubMedCrossRefGoogle Scholar
  29. 29.
    Carlomagno G, Unfer V, Roseff S: The D-chiro-inositol paradox in the ovary. Fertil Steril 2011, 95: 2515–2516. 10.1016/j.fertnstert.2011.05.027PubMedCrossRefGoogle Scholar
  30. 30.
    Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F: Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci 2011, 15: 509–514.PubMedGoogle Scholar
  31. 31.
    Cheang KI, Baillargeon JP, Essah PA, Ostlund RE, Apridonize T, Islam L, Nestler JE: Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome. Metabolism 2008, 57: 1390–1397. 10.1016/j.metabol.2008.05.008PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Palomba S, Falbo A, Di Cello A, Cappiello F, Tolino A, Zullo F: Does metformin affect the ovarian response to gonadotropins for in vitro fertilization treatment in patients with polycystic ovary syndrome and reduced ovarian reserve? A randomized controlled trial. Fertil Steril 2011, 96: 1128–1133. 10.1016/j.fertnstert.2011.08.020PubMedCrossRefGoogle Scholar
  33. 33.
    Baillargeon JP, Iuorno MJ, Jakubowicz DJ, Apridonidze T, He N, Nestler JE: Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004, 89: 242–249. 10.1210/jc.2003-030437PubMedCrossRefGoogle Scholar

Copyright information

© Isabella and Raffone; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  1. 1.C.I.S. Reproductive MedicineLamezia TermeItaly
  2. 2.Obstetrics and Gynecology DepartmentG. Martino HospitalMessinaItaly

Personalised recommendations