Archives of Gynecology and Obstetrics

, Volume 288, Issue 6, pp 1405–1411 | Cite as

The combined therapy myo-inositol plus d-chiro-inositol, rather than d-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial

  • Sandra Colazingari
  • Mariangela Treglia
  • Robert Najjar
  • Arturo Bevilacqua
Reproductive Medicine

Abstract

Purpose

The present study aims to investigate the effects of the combined therapy myo-inositol (MI) plus d-chiro-inositol (DCI) or d-chiro-inositol treatment in oocyte quality.

Methods

Polycystic ovary syndrome (PCOS) women undergoing IVF-ET were treated with myo-inositol combined with d-chiro-inositol in the physiological ratio (1.1 g myo-inositol plus 27.6 mg of d-chiro-inositol; INOFOLIC® combi Lo.Li.pharma) or d-chiro-inositol alone (500 mg; Interquim, s.a., Barcelona, Spain) to evaluate the umber of morphological mature oocytes, total International Units (IU) of recombinant FSH administered and the number of grade 1 embryos.

Results

The data clearly showed that only the combined therapy was able to improve oocyte and embryo quality, as well as pregnancy rates, in PCOS women undergoing IVF-ET.

Conclusion

The present paper further supports the hypothesis that MI plays a crucial role in the ovary in PCOS women. In particular, due to the physiological role played by MI and DCI, the combined therapy should represent a better choice.

Keywords

Myo-inositol d-chiro-inositol Oocyte quality IVF Embryo quality 

Notes

Conflict of interest

None.

References

  1. 1.
    van Loendersloot LL, van Wely M, Limpens J, Bossuyt PM, Repping S, van der Veen F (2010) Predictive factors in in vitro fertilization (IVF): a systematic review and meta-analysis. Hum Reprod Update 16(6):577–589. doi: 10.1093/humupd/dmq015 PubMedCrossRefGoogle Scholar
  2. 2.
    Rienzi L, Vajta G, Ubaldi F (2010) Predictive value of oocyte morphology in human IVF: a systematic review of the literature. Hum Reprod Update 17(1):34–45. doi: 10.1093/humupd/dmq029 PubMedCrossRefGoogle Scholar
  3. 3.
  4. 4.
    Revelli A, Delle Piane L, Casano S, Molinari E, Massobrio M, Rinaudo P (2009) Follicular fluid content and oocyte quality: from single biochemical markers to metabolomics. Reprod Biol Endocrinol 7:40. doi: 10.1186/1477-7827-7-40 PubMedCrossRefGoogle Scholar
  5. 5.
    Chiu TT, Rogers MS, Law EL, Briton-Jones CM, Cheung LP, Haines CJ (2002) Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod 17(6):1591–1596PubMedCrossRefGoogle Scholar
  6. 6.
    Tamura H, Nakamura Y, Korkmaz A, Manchester LC, Tan DX, Sugino N, Reiter RJ (2009) Melatonin and the ovary: physiological and pathophysiological implications. Fertil Steril 92(1):328–343. doi: 10.1016/j.fertnstert.2008.05.016 PubMedCrossRefGoogle Scholar
  7. 7.
    Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, De Santis L (2009) Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. Fertil Steril 91(5):1750–1754. doi: 10.1016/j.fertnstert.2008.01.088 PubMedCrossRefGoogle Scholar
  8. 8.
    Unfer V, Raffone E, Rizzo P, Buffo S (2011) Effect of a supplementation with myo-inositol plus melatonin on oocyte quality in women who failed to conceive in previous in vitro fertilization cycles for poor oocyte quality: a prospective, longitudinal, cohort study. Gynecol Endocrinol. doi: 10.3109/09513590.2011.564687
  9. 9.
    Rizzo P, Raffone E, Benedetto V (2010) Effect of the treatment with myo-inositol plus folic acid plus melatonin in comparison with a treatment with myo-inositol plus folic acid on oocyte quality and pregnancy outcome in IVF cycles. A prospective, clinical trial. Eur Rev Med Pharmacol Sci 14(6):555–561PubMedGoogle Scholar
  10. 10.
    Chattopadhayay R, Ganesh A, Samanta J, Jana SK, Chakravarty BN, Chaudhury K (2010) Effect of follicular fluid oxidative stress on meiotic spindle formation in infertile women with polycystic ovarian syndrome. Gynecol Obstet Invest 69(3):197–202. doi: 10.1159/000270900 PubMedCrossRefGoogle Scholar
  11. 11.
    Berker B, Kaya C, Aytac R, Satiroglu H (2009) Homocysteine concentrations in follicular fluid are associated with poor oocyte and embryo qualities in polycystic ovary syndrome patients undergoing assisted reproduction. Hum Reprod 24(9):2293–2302. doi: 10.1093/humrep/dep069 PubMedCrossRefGoogle Scholar
  12. 12.
    Papaleo E, Unfer V, Baillargeon JP, Chiu TT (2009) Contribution of myo-inositol to reproduction. Eur J Obstet Gynecol Reprod Biol 147(2):120–123. doi: 10.1016/j.ejogrb.2009.09.008 PubMedCrossRefGoogle Scholar
  13. 13.
    Huang LC, Fonteles MC, Houston DB, Zhang C, Larner J (1993) 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 132(2):652–657PubMedCrossRefGoogle Scholar
  14. 14.
    Zacche MM, Caputo L, Filippis S, Zacche G, Dindelli M, Ferrari A (2009) Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome. Gynecol Endocrinol 25(8):508–513. doi: 10.1080/09513590903015544 PubMedCrossRefGoogle Scholar
  15. 15.
    Costantino D, Minozzi G, Minozzi E, Guaraldi C (2009) Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci 13(2):105–110PubMedGoogle Scholar
  16. 16.
    Genazzani AD, Lanzoni C, Ricchieri F, Jasonni VM (2008) Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecol Endocrinol 24(3):139–144. doi: 10.1080/09513590801893232 PubMedCrossRefGoogle Scholar
  17. 17.
    Papaleo E, Unfer V, Baillargeon JP, De Santis L, Fusi F, Brigante C, Marelli G, Cino I, Redaelli A, Ferrari A (2007) Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol 23(12):700–703. doi: 10.1080/09513590701672405 PubMedCrossRefGoogle Scholar
  18. 18.
    Gerli S, Papaleo E, Ferrari A, Di Renzo GC (2007) Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci 11(5):347–354PubMedGoogle Scholar
  19. 19.
    Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G (1999) Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 340(17):1314–1320. doi: 10.1056/NEJM199904293401703 PubMedCrossRefGoogle Scholar
  20. 20.
    Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino F (2011) Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci 15(5):509–514PubMedGoogle Scholar
  21. 21.
    Minozzi M, Costantino D, Guaraldi C, Unfer V (2011) The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome. Gynecol Endocrinol. doi: 10.3109/09513590.2011.564685
  22. 22.
    Cheang KI, Baillargeon JP, Essah PA, Ostlund RE Jr, Apridonize T, Islam L, Nestler JE (2008) Insulin-stimulated release of d-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome. Metabolism 57(10):1390–1397. doi: 10.1016/j.metabol.2008.05.008 PubMedCrossRefGoogle Scholar
  23. 23.
    Unfer V, Carlomagno G, Rizzo P, Raffone E, Roseff S (2011) 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 15(4):452–457PubMedGoogle Scholar
  24. 24.
    Pak Y, Huang LC, Lilley KJ, Larner J (1992) In vivo conversion of [3H]myoinositol to [3H]chiroinositol in rat tissues. J Biol Chem 267(24):16904–16910PubMedGoogle Scholar
  25. 25.
    Larner J (2002) d-chiro-inositol—its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 3(1):47–60PubMedCrossRefGoogle Scholar
  26. 26.
    Saito T, Jones CC, Huang S, Czech MP, Pilch PF (2007) The interaction of Akt with APPL1 is required for insulin-stimulated Glut4 translocation. J Biol Chem 282(44):32280–32287. doi: 10.1074/jbc.M704150200 PubMedCrossRefGoogle Scholar
  27. 27.
    Broussard JA, Lin WH, Majumdar D, Anderson B, Eason B, Brown CM, Webb DJ (2012) The endosomal adaptor protein APPL1 impairs the turnover of leading edge adhesions to regulate cell migration. Mol Biol Cell 23(8):1486–1499. doi: 10.1091/mbc.E11-02-0124 PubMedCrossRefGoogle Scholar
  28. 28.
    Borini A, Sciajno R, Bianchi V, Sereni E, Flamigni C, Coticchio G (2006) Clinical outcome of oocyte cryopreservation after slow cooling with a protocol utilizing a high sucrose concentration. Hum Reprod 21(2):512–517. doi: 10.1093/humrep/dei346 PubMedCrossRefGoogle Scholar
  29. 29.
    Van de Velde H, Nagy ZP, Joris H, De Vos A, Van Steirteghem AC (1997) Effects of different hyaluronidase concentrations and mechanical procedures for cumulus cell removal on the outcome of intracytoplasmic sperm injection. Hum Reprod 12(10):2246–2250PubMedCrossRefGoogle Scholar
  30. 30.
    De Santis L, Cino I, Rabellotti E, Papaleo E, Calzi F, Fusi FM, Brigante C, Ferrari A (2007) Oocyte cryopreservation: clinical outcome of slow-cooling protocols differing in sucrose concentration. Reprod Biomed Online 14(1):57–63PubMedCrossRefGoogle Scholar
  31. 31.
    Isabella R, Raffone E (2012) Does ovary need d-chiro-inositol? J ovarian res 5(1):14. doi: 10.1186/1757-2215-5-14 PubMedCrossRefGoogle Scholar
  32. 32.
    Agranoff BW (2009) Turtles all the way: reflections on myo-inositol. J Biol Chem 284(32):21121–21126. doi: 10.1074/jbc.X109.004747 PubMedCrossRefGoogle Scholar
  33. 33.
    Kutateladze TG (2010) Translation of the phosphoinositide code by PI effectors. Nat Chem Biol 6(7):507–513. doi: 10.1038/nchembio.390 PubMedCrossRefGoogle Scholar
  34. 34.
    Lahiri Majumder A, Biswas BB (eds) (2006) Biology of Inositols and Phosphoinositides. Subcellular Biochemistry, vol 39. Springer, New yorkGoogle Scholar
  35. 35.
    Berridge MJ (2009) Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta 1793(6):933–940. doi: 10.1016/j.bbamcr.2008.10.005 PubMedCrossRefGoogle Scholar
  36. 36.
    Chiu TT, Tam PP (1992) A correlation of the outcome of clinical in vitro fertilization with the inositol content and embryotrophic properties of human serum. J Assist Reprod Genet 9(6):524–530PubMedCrossRefGoogle Scholar
  37. 37.
    Beemster P, Groenen P, Steegers-Theunissen R (2002) Involvement of inositol in reproduction. Nutr Rev 60(3):80–87PubMedCrossRefGoogle Scholar
  38. 38.
    Goud PT, Goud AP, Leybaert L, Van Oostveldt P, Mikoshiba K, Diamond MP, Dhont M (2002) Inositol 1,4,5-trisphosphate receptor function in human oocytes: calcium responses and oocyte activation-related phenomena induced by photolytic release of InsP(3) are blocked by a specific antibody to the type I receptor. Mol Hum Reprod 8(10):912–918PubMedCrossRefGoogle Scholar
  39. 39.
    Chiu TT, Rogers MS, Briton-Jones C, Haines C (2003) Effects of myo-inositol on the in vitro maturation and subsequent development of mouse oocytes. Hum Reprod 18(2):408–416PubMedCrossRefGoogle Scholar
  40. 40.
    Gerli S, Mignosa M, Di Renzo GC (2003) 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 7(6):151–159PubMedGoogle Scholar
  41. 41.
    Carlomagno G, Unfer V, Roseff S (2011) The d-chiro-inositol paradox in the ovary. Fertil Steril 95(8):2515–2516. doi: 10.1016/j.fertnstert.2011.05.027 PubMedCrossRefGoogle Scholar
  42. 42.
    Nechamen CA, Thomas RM, Cohen BD, Acevedo G, Poulikakos PI, Testa JR, Dias JA (2004) Human follicle-stimulating hormone (FSH) receptor interacts with the adaptor protein APPL1 in HEK 293 cells: potential involvement of the PI3K pathway in FSH signaling. Biol Reprod 71(2):629–636. doi: 10.1095/biolreprod.103.025833 PubMedCrossRefGoogle Scholar
  43. 43.
    Ma XW, Ding S, Ma XD, Gu N, Guo XH (2011) Genetic variability in adapter proteins with APPL1/2 is associated with the risk of coronary artery disease in type 2 diabetes mellitus in Chinese Han population. Chin Med J (Engl) 124(22):3618–3621Google Scholar
  44. 44.
    Raffone E, Rizzo P, Benedetto V (2010) Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol 26(4):275–280. doi: 10.3109/09513590903366996 PubMedCrossRefGoogle Scholar
  45. 45.
    Tian L, Luo N, Zhu X, Chung BH, Garvey WT, Fu Y (2012) Adiponectin–AdipoR1/2–APPL1 signaling axis suppresses human foam cell formation: differential ability of AdipoR1 and AdipoR2 to regulate inflammatory cytokine responses. Atherosclerosis 221(1):66–75. doi: 10.1016/j.atherosclerosis.2011.12.014 PubMedCrossRefGoogle Scholar
  46. 46.
    Bohdanowicz M, Balkin DM, De Camilli P, Grinstein S (2012) Recruitment of OCRL and Inpp 5B to phagosomes by Rab5 and APPL1 depletes phosphoinositides and attenuates Akt signaling. Mol Biol Cell 23(1):176–187. doi: 10.1091/mbc.E11-06-0489 PubMedCrossRefGoogle Scholar
  47. 47.
    Pal L, Jindal S, Witt BR, Santoro N (2008) Less is more: increased gonadotropin use for ovarian stimulation adversely influences clinical pregnancy and live birth after in vitro fertilization. Fertil Steril 89(6):1694–1701. doi: 10.1016/j.fertnstert.2007.05.055 PubMedCrossRefGoogle Scholar
  48. 48.
    Pak Y, Paule CR, Bao YD, Huang LC, Larner J (1993) Insulin stimulates the biosynthesis of chiro-inositol-containing phospholipids in a rat fibroblast line expressing the human insulin receptor. Proc Natl Acad Sci USA 90(16):7759–7763PubMedCrossRefGoogle Scholar
  49. 49.
    Larner J, Brautigan DL, Thorner MO (2010) d-chiro-inositol glycans in insulin signaling and insulin resistance. Mol Med 16 (11–12):543–552. doi: 10.2119/molmed.2010.00107 Google Scholar
  50. 50.
    Larner J (2001) d-chiro-inositol in insulin action and insulin resistance-old-fashioned biochemistry still at work. IUBMB Life 51(3):139–148. doi: 10.1080/152165401753544205 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Sandra Colazingari
    • 1
    • 2
  • Mariangela Treglia
    • 3
  • Robert Najjar
    • 3
  • Arturo Bevilacqua
    • 1
    • 2
  1. 1.Department of Psychology, Section of NeuroscienceUniversity of Rome “Sapienza”RomeItaly
  2. 2.Centro di Ricerca in Neurobiologia Daniel Bovet (CRiN)RomeItaly
  3. 3.Leda Fertility CenterRomeItaly

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