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Archives of Gynecology and Obstetrics

, Volume 298, Issue 4, pp 675–684 | Cite as

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

  • Antonio Simone Laganà
  • Amerigo Vitagliano
  • Marco Noventa
  • Guido Ambrosini
  • Rosario D’Anna
Review

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.

Keywords

Myo-inositol In vitro fertilization Recombinant follicle-stimulating hormone Controlled ovarian hyperstimulation 

Notes

Author 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.

Funding

The work was not supported by any grant/fund.

Compliance with ethical standards

Conflict of interest

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.

Ethical approval

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

Informed consent

For this type of study, formal consent is not required.

References

  1. 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 CrossRefPubMedGoogle Scholar
  2. 2.
    Hatch AJ, York JD (2010) SnapShot: inositol phosphates. Cell 143(1030–1030):e1.  https://doi.org/10.1016/j.cell.2010.11.045 CrossRefGoogle Scholar
  3. 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 CrossRefPubMedGoogle Scholar
  4. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 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 CrossRefPubMedGoogle Scholar
  7. 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 CrossRefPubMedGoogle Scholar
  8. 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 CrossRefPubMedGoogle Scholar
  9. 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 CrossRefPubMedGoogle Scholar
  10. 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 CrossRefPubMedGoogle Scholar
  11. 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 CrossRefPubMedGoogle Scholar
  12. 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 CrossRefPubMedGoogle Scholar
  13. 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 CrossRefPubMedGoogle Scholar
  14. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 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. 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 14:555–561Google Scholar
  17. 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 15:509–514PubMedGoogle Scholar
  18. 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 15:452–457PubMedGoogle Scholar
  19. 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 CrossRefGoogle Scholar
  20. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Schillaci R, Mangione D, Lo Monte G, Vassiliadis A (2012) Inositol supplementation and IVF outcome: preliminary data. Ital J Gynaecol Obstet 21:38–44Google Scholar
  22. 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 CrossRefPubMedGoogle Scholar
  23. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 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 81:19–25Google Scholar
  26. 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 CrossRefPubMedGoogle Scholar
  27. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 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 CrossRefGoogle Scholar
  29. 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 CrossRefPubMedGoogle Scholar
  30. 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 CrossRefPubMedGoogle Scholar
  31. 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 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and Gynecology“Filippo Del Ponte” Hospital, University of InsubriaVareseItaly
  2. 2.Department of Woman and Child HealthUniversity of PaduaPaduaItaly
  3. 3.Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood “G. Barresi”University of MessinaMessinaItaly

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