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Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Purpose

To evaluate whether oral myo-inositol supplementation (MI) is able to reduce the amount of gonadotropins (GA) and the length of controlled ovarian hyperstimulation (SL) in both Polycystic Ovarian Syndrome (PCOS) and non-PCOS women undergoing in vitro fertilization (IVF).

Methods

We performed a systematic review (PROSPERO ID: CRD42017069439) of randomized controlled trials (RCTs). We searched articles published in English between January 1985 to August 2017, using the combination of the Medical Subject Headings “Inositol” with “Ovulation Induction”, “follicle-stimulating hormone, human, with HCG C-terminal peptide”, “Reproductive Techniques, Assisted”, and “Fertilization in Vitro”. We collected data about GA and SL comparing MI to no treatment or d-Chiro-Inositol (DCI) supplementation (controls). A subgroup analysis was performed to evaluate selected outcomes in PCOS and non-PCOS women.

Results

We included 8 studies embedding 812 participants. We found a reduction in GA (p < 0.00001) and SL (p = 0.0007) in patients receiving MI with respect to controls. MI was effective in both PCOS (p < 0.00001) and non-PCOS women (p = 0.02) in reducing GA; conversely, MI supplementation decreased the SL only in PCOS women (p < 0.00001).

Conclusion

During IVF, MI is effective in both PCOS and non-PCOS women in saving gonadotropins, but reduces efficiently SL only in PCOS women.

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References

  1. Bizzarri M, Fuso A, Dinicola S, Cucina A, Bevilacqua A (2016) Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opin Drug Metab Toxicol 12:1181–1196. https://doi.org/10.1080/17425255.2016.1206887

    Article  CAS  PubMed  Google Scholar 

  2. Hatch AJ, York JD (2010) SnapShot: inositol phosphates. Cell 143(1030–1030):e1. https://doi.org/10.1016/j.cell.2010.11.045

    Article  CAS  Google Scholar 

  3. Di Paolo G, De Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–657. https://doi.org/10.1038/nature05185

    Article  CAS  PubMed  Google Scholar 

  4. Sortino MA, Salomone S, Carruba MO, Drago F (2017) Polycystic ovary syndrome: insights into the therapeutic approach with inositols. Front Pharmacol 8:341. https://doi.org/10.3389/fphar.2017.00341

    Article  PubMed  PubMed Central  Google Scholar 

  5. Chakraborty A, Kim S, Snyder SH (2011) Inositol pyrophosphates as mammalian cell signals. Sci Signal 4:re1. https://doi.org/10.1126/scisignal.2001958

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Noventa M, Vitagliano A, Quaranta M, Borgato S, Abdulrahim B, Gizzo S (2016) Preventive and therapeutic role of dietary inositol supplementation in periconceptional period and during pregnancy: a summary of evidences and future applications. Reprod Sci 23:278–288. https://doi.org/10.1177/1933719115594018

    Article  CAS  PubMed  Google Scholar 

  7. Paul C, Laganà AS, Maniglio P, Triolo O, Brady DM (2016) Inositol’s and other nutraceuticals’ synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives. Gynecol Endocrinol 32:431–438. https://doi.org/10.3109/09513590.2016

    Article  CAS  PubMed  Google Scholar 

  8. Vitagliano A, Noventa M, Gizzo S (2015) Is it time to consider patients suffering from endometriosis-related infertility as “novel candidates” for targeted peri-conceptional d-chiro inositol supplementation? Hypothesis, rationale and some considerations. J Assist Reprod Genet 32:407–408. https://doi.org/10.1007/s10815-014-0412-z

    Article  PubMed  Google Scholar 

  9. Pizzo A, Laganà AS, Barbaro L (2014) Comparison between effects of myo-inositol and d-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol 30:205–208. https://doi.org/10.3109/09513590.2013.860120

    Article  CAS  PubMed  Google Scholar 

  10. 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 91:1750–1754. https://doi.org/10.1016/j.fertnstert.2008.01.088

    Article  CAS  PubMed  Google Scholar 

  11. Colazingari S, Treglia M, Najjar R, Bevilacqua A (2013) 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. https://doi.org/10.1007/s00404-013-2855-3

    Article  CAS  PubMed  Google Scholar 

  12. Pacchiarotti A, Carlomagno G, Antonini G, Pacchiarotti A (2016) Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome. Gynecol Endocrinol 32:69–73. https://doi.org/10.3109/09513590.2015.1101444

    Article  PubMed  Google Scholar 

  13. Mendoza N, Pérez L, Simoncini T, Genazzani A (2017) Inositol supplementation in women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection: a systematic review and meta-analysis of randomized controlled trials. Reprod Biomed Online 35:529–535. https://doi.org/10.1016/j.rbmo.2017.07.005

    Article  CAS  PubMed  Google Scholar 

  14. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097

    Article  PubMed  PubMed Central  Google Scholar 

  15. Higgins JPT, Green S (eds) (2011) Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from http://handbook.cochrane.org

  16. 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 14:555–561

    CAS  Google Scholar 

  17. 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 15:509–514

    CAS  PubMed  Google Scholar 

  18. 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 15:452–457

    CAS  PubMed  Google Scholar 

  19. Carlomagno G, Oliva MM, Roseff SJ, Unfer V (2012) Myo-inositol: ovarian stimulation and IVF outcomes. Fertil Steril 98:S74–S75. https://doi.org/10.1016/j.fertnstert.2012.07.270

    Article  Google Scholar 

  20. Lisi F, Carfagna P, Oliva MM, Rago R, Lisi R, Poverini R, Manna C, Vaquero E, Caserta D, Raparelli V, Marci R, Moscarini M (2012) Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study. Reprod Biol Endocrinol 10:52. https://doi.org/10.1186/1477-7827-10-52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Schillaci R, Mangione D, Lo Monte G, Vassiliadis A (2012) Inositol supplementation and IVF outcome: preliminary data. Ital J Gynaecol Obstet 21:38–44

    Google Scholar 

  22. Artini PG, Di Berardino OM, Papini F, Genazzani AD, Simi G, Ruggiero M, Cela V (2013) Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol 29:375–379. https://doi.org/10.3109/09513590.2012.743020

    Article  CAS  PubMed  Google Scholar 

  23. Caprio F, D’Eufemia MD, Trotta C, Campitiello MR, Ianniello R, Mele D, Colacurci N (2015) Myo-inositol therapy for poor-responders during IVF: a prospective controlled observational trial. J Ovarian Res 8:37. https://doi.org/10.1186/s13048-015-0167-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lesoine B, Regidor PA (2016) Prospective randomized study on the influence of myoinositol in PCOS women undergoing IVF in the improvement of oocyte quality, fertilization rate, and embryo quality. Int J Endocrinol 2016:4378507. https://doi.org/10.1155/2016/4378507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81:19–25

    Google Scholar 

  26. Unfer V, Carlomagno G, Dante G, Facchinetti F (2012) Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials. Gynecol Endocrinol 28:509–515. https://doi.org/10.3109/09513590.2011.650660

    Article  CAS  PubMed  Google Scholar 

  27. Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F (2016) Effects of Inositol(s) in women with PCOS: a systematic review of randomized controlled trials. Int J Endocrinol 2016:1849162. https://doi.org/10.1155/2016/1849162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zheng X, Lin D, Zhang Y, Lin Y, Song J, Li S, Sun Y (2017) Inositol supplement improves clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. Medicine (Baltimore) 96:e8842. https://doi.org/10.1097/MD.0000000000008842

    Article  CAS  Google Scholar 

  29. Busnelli A, Papaleo E, Del Prato D, La Vecchia I, Iachini E, Paffoni A, Candiani M, Somigliana E (2015) A retrospective evaluation of prognosis and cost-effectiveness of IVF in poor responders according to the Bologna criteria. Hum Reprod 30:315–322. https://doi.org/10.1093/humrep/deu319

    Article  PubMed  Google Scholar 

  30. Zivi E, Simon A, Laufer N (2010) Ovarian hyperstimulation syndrome: definition, incidence, and classification. Semin Reprod Med 28:441–447. https://doi.org/10.1055/s-0030-1265669

    Article  CAS  PubMed  Google Scholar 

  31. Csokmay JM, Yauger BJ, Henne MB, Armstrong AY, Queenan JT, Segars JH (2010) Cost analysis model of outpatient management of ovarian hyperstimulation syndrome with paracentesis: “Tap early and often” versus hospitalization. Fertil Steril 93:167–173. https://doi.org/10.1016/j.fertnstert.2008.09.054

    Article  PubMed  Google Scholar 

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Funding

The work was not supported by any grant/fund.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Piazza Biroldi 1, 21100, Varese, Italy

    Antonio Simone Laganà

  2. Department of Woman and Child Health, University of Padua, Padua, Italy

    Amerigo Vitagliano, Marco Noventa & Guido Ambrosini

  3. Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood “G. Barresi”, University of Messina, Messina, Italy

    Rosario D’Anna

Authors
  1. Antonio Simone Laganà
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  2. Amerigo Vitagliano
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  3. Marco Noventa
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  4. Guido Ambrosini
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  5. Rosario D’Anna
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Contributions

ASL: designed the systematic review and lead its development. AV and MN: performed the meta-analysis of retrieved data. GA: edited the manuscript. RD: supervised the development of the systematic review and meta-analysis and gave the final approval. All the authors concurred to screen the literature, include relevant data and write the manuscript. All the authors fulfil the International Committee of Medical Journal Editors (ICMJE) criteria.

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Correspondence to Antonio Simone Laganà.

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The authors have no proprietary, financial, professional, or other personal interest of any nature in any product, service, or company. The authors alone are responsible for the content and writing of the paper.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Laganà, A.S., Vitagliano, A., Noventa, M. et al. Myo-inositol supplementation reduces the amount of gonadotropins and length of ovarian stimulation in women undergoing IVF: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 298, 675–684 (2018). https://doi.org/10.1007/s00404-018-4861-y

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