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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

  • Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

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.

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References

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  3. UNCE (2005) http://www.unece.org/stats/trends2005/family.htm

  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

    Article  PubMed  Google Scholar 

  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):1591–1596

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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. 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):555–561

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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):652–657

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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):105–110

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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):347–354

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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):509–514

    PubMed  CAS  Google Scholar 

  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. 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

    Article  PubMed  CAS  Google Scholar 

  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):452–457

    PubMed  CAS  Google Scholar 

  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):16904–16910

    PubMed  CAS  Google Scholar 

  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):47–60

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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):2246–2250

    Article  PubMed  Google Scholar 

  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):57–63

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  33. Kutateladze TG (2010) Translation of the phosphoinositide code by PI effectors. Nat Chem Biol 6(7):507–513. doi:10.1038/nchembio.390

    Article  PubMed  CAS  Google Scholar 

  34. Lahiri Majumder A, Biswas BB (eds) (2006) Biology of Inositols and Phosphoinositides. Subcellular Biochemistry, vol 39. Springer, New york

  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

    Article  PubMed  CAS  Google Scholar 

  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):524–530

    Article  PubMed  CAS  Google Scholar 

  37. Beemster P, Groenen P, Steegers-Theunissen R (2002) Involvement of inositol in reproduction. Nutr Rev 60(3):80–87

    Article  PubMed  Google Scholar 

  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):912–918

    Article  PubMed  CAS  Google Scholar 

  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):408–416

    Article  PubMed  CAS  Google Scholar 

  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):151–159

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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):3618–3621

    CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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):7759–7763

    Article  PubMed  CAS  Google Scholar 

  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. 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

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Psychology, Section of Neuroscience, University of Rome “Sapienza”, Via dei Marsi 78, 00185, Rome, Italy

    Sandra Colazingari & Arturo Bevilacqua

  2. Centro di Ricerca in Neurobiologia Daniel Bovet (CRiN), Rome, Italy

    Sandra Colazingari & Arturo Bevilacqua

  3. Leda Fertility Center, Via del Giordano 34, 00144, Rome, Italy

    Mariangela Treglia & Robert Najjar

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  1. Sandra Colazingari
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  2. Mariangela Treglia
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Correspondence to Arturo Bevilacqua.

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Colazingari, S., Treglia, M., Najjar, R. et al. 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. Arch Gynecol Obstet 288, 1405–1411 (2013). https://doi.org/10.1007/s00404-013-2855-3

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  • DOI: https://doi.org/10.1007/s00404-013-2855-3

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