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Journal of Endocrinological Investigation

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15-07-2024 | Endocrinology and Reproductive Medicine | Consensus Statement

Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)—Women’s Endocrinology

Authors: Costanzo Moretti, Marco Bonomi, Paola Dionese, Silvia Federici, Anna Maria Fulghesu, Jacopo Giannelli, Roberta Giordano, Laura Guccione, Elisa Maseroli, Paolo Moghetti, Roberto Mioni, Rosario Pivonello, Chiara Sabbadin, Carla Scaroni, Massimo Tonacchera, Nunzia Verde, Linda Vignozzi, Alessandra Gambineri

Published in: Journal of Endocrinological Investigation | Issue 9/2024

Abstract

Purpose

To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process.

Methods

A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes.

Results

A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM.

Conclusion

This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.

Kiani AK, Paolacci S, Calogero AE, Cannarella R, Di Renzo GC, Gerli S, Della Morte C, Busetto GM, De Berbardinis E, Del Giudice F, Stuppia L, Facchinetti F, Dinicola S, Bertelli M (2021) From Myo-inositol to D-chiro-inositol molecular pathways. Eur Rev Med Pharmacol Sci 25:2390–2402. https://doi.org/10.26355/eurrev_202103_25279CrossRefPubMed

Laganà AS, Rossetti P, Buscema M, La Vignera S, Condorelli RA, Gullo G, Granese R, Triolo O (2016) Metabolism and ovarian function in pcos women: a therapeutic approach with inositols. Int J Endocrinol. https://doi.org/10.1155/2016/6306410CrossRefPubMedPubMedCentral

Pak Y, Huang LC, Lilley KJ, Larner J (1992) In vivo conversion of [3H]myoinositol to [3H]chiroinositol in rat tissues. J Biol Chem 267:16904–16910 (PMID: 1387397)CrossRefPubMed

Larner J (2002) D-chiro-inositol–its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 3:47–60. https://doi.org/10.1080/15604280212528CrossRefPubMedPubMedCentral

Dinicola S, Unfer V, Facchinetti F et al (2021) Inositols: from established knowledge to novel approaches. Int J Mol Sci 22:10575. https://doi.org/10.3390/ijms221910575CrossRefPubMedPubMedCentral

Baldassarre MPA, Di Tomo P, Centorame G, Pandolfi A, Di Pietro N, Consoli A, Formoso G (2021) Myoinositol reduces inflammation and oxidative stress in human endothelial cells exposed in vivo to chronic hyperglycemia. Nutrients 13:2210. https://doi.org/10.3390/nu13072210CrossRefPubMedPubMedCentral

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/10.3109/09513590.2013.860120CrossRefPubMed

Facchinetti F, Dante G, Neri I (2016) The ratio of MI to DCI and Its Impact in the treatment of polycystic ovary syndrome: experimental and literature evidences. Front Gynecol Endocrinol. https://doi.org/10.1007/978-3-319-23865-4_13CrossRef

Bizzarri M, Monti N, Piombarolo A, Angeloni A, Verna R (2023) Myo-inositol and D-Chiro-inositol as modulators of ovary steroidogenesis: a narrative review. Nutrients 15:1–14. https://doi.org/10.3390/nu15081875CrossRef

10.

Berridge MJ (2009) Inositol trisphosphate and calcium signalling mechanisms. Biochim Biophys Acta 1793:933–940. https://doi.org/10.1016/j.bbamcr.2008.10.005CrossRefPubMed

11.

Hallman M, Arjomaa P, Hoppu K (1987) Inositol supplementation in respiratory distress syndrome: relationship between serum concentration, renal excretion, and lung effluent phospholipids. J Pediatr 110:604–610. https://doi.org/10.1016/s0022-3476(87)80561-9CrossRefPubMed

12.

Unfer V, Carlomagno G, Papaleo E, Vailati S, Candiani M, Baillargeon J-P (2014) Hyperinsulinemia alters myioinositol to d-chiroinositol ratio in the follicular fluid of of patients with PCOS. Reprod Sci 21:854–858. https://doi.org/10.1177/1933719113518985CrossRefPubMed

13.

Facchinetti F, Unfer V, Dewailly D, Kamenov ZA, Diamanti-Kandarakis E, Laganà AS, Nestler JE, Soulage CO, Group of ’Inositol in PCOS and Reproduction (2020) Inositols in polycystic ovary syndrome: an overview on the advances. Trends Endocrinol Metab 31(435):447. https://doi.org/10.1016/j.tem.2020.02.002CrossRef

14.

Ravanos K, Monastra G, Pavlidou T, Goudakou M, Prapas N (2017) Can high levels of D-chiro-inositol in follicular fluid exert detrimental effects in blastocyst quality? Eur Rev Med Pharmacol Sci 21:5491–5498. https://doi.org/10.26355/eurrev_201712_13940CrossRefPubMed

15.

Conway G, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Franks S, Gambineri A, Kelestimur F, Macut D, Micic D, Pasquali R, Pfeifer M, Pignatelli D, Pugeat M, Yildiz BO, ESE PCOS Special Interest Group (2014) The polycystic ovary syndrome: a position statement from the European Society of Endocrinology. Eur J Endocrinol 171(P1):29. https://doi.org/10.1530/EJE-14-0253CrossRef

16.

Fedeli V, Catizone A, Querqui A, Unfer V, Bizzarri M (2023) The role of inositols in the Hyperandrogenic phenotypes of PCOS: a re-reading of larner’s results. Int J Mol Sci 24:6296. https://doi.org/10.3390/ijms24076296CrossRefPubMedPubMedCentral

17.

Nestler JE, Unfer V (2015) Reflections of inositol(s) for PCOS therapy: steps toward success. Gynecol Endocrinol 31:501–505. https://doi.org/10.3109/09513590.2015.1054802CrossRefPubMed

18.

Scheider S (2015) Inositol transport proteins. FEBS Lett 589:1049–1058. https://doi.org/10.1016/j.febslet.2015.03.012CrossRef

19.

Gambioli R, Forte G, Buzzaccarini G, Unfer V, Laganà AS (2021) Myo-inositol as a key supporter of fertility and physiological gestation. Pharmaceuticals 14:504. https://doi.org/10.3390/ph14060504CrossRefPubMedPubMedCentral

20.

Monastra G, Vucenik I, Harrath AH, Alwasel SH, Kamenov ZA, Laganà AS, Monti N, Fedeli V, Bizzarri M (2021) PCOS and inositols: controversial results and necessary clarifications. Basic Differ Between D-Chiro and Myo-Inositol Front Endocrinol (Lausanne). https://doi.org/10.3389/fendo.2021.660381CrossRefPubMed

21.

Swiglo BA, Murad MH, Schünemann HJ, Kunz R, Vigersky RA, Guyatt GH, Montori VM (2008) A case for clarity, consistency, and helpfulness: state-of-the-art clinical practice guidelines in endocrinology using the grading of recommendations, assessment, development, and evaluation system. J Clin Endocrinol Metab 93:666–673. https://doi.org/10.1210/jc.2007-1907CrossRefPubMed

22.

Van Trotsenburg P, Stoupa A, Léger J, Rohrer T, Peters C, Fugazzola L, Cassio A, Heinrichs C, Beauloye V, Pohlenz J, Rodien P, Coutant R, Szinnai G, Murray P, Bartés B, Luton D, Salerno M, de Sanctis L, Vigone M, Krude H, Persani L, Polak M (2021) Congenital Hypothyroidism: a 2020–2021 consensus guidelines update-an endo-european reference network initiative endorsed by the European society for pediatric endocrinology and the European society for endocrinology. Thyroid 31:387–419. https://doi.org/10.1089/thy.2020.0333CrossRefPubMedPubMedCentral

23.

Jaye A, Zhilin L, Yi Athena R, Wang-Song W, Wei Z, Shlomit K, Clifford L, Cecilia V, William G, JoAnne R (2016) Enhanced inflammatory transcriptome in the granulosa cells of women with polycystic ovarian syndrome. J Clin Endocrinol Metab 101:3459–3468. https://doi.org/10.1210/jc.2015-4275CrossRef

24.

Franceschi C, Garagnani P, Parini P, Giuliani C (2018) Santoro A (2018) Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol 14:576–590. https://doi.org/10.1038/s41574-018-0059-4CrossRefPubMed

25.

Emekçi Özlen Ö, Ali Cenk Ö, Erkan Ç, Recep Emre O, Bülent G (2017) Myo-inositol administration positively effects ovulation induction and intrauterine insemination in patients with polycystic ovary syndrome: a prospective, controlled, randomized trial. Gynecol Endocrinol 33:524–528. https://doi.org/10.1080/09513590.2017.1296127CrossRef

26.

Facchinetti F, Cavalli P, Copp AJ, D’Anna R, Kandaraki E, Greene NDE, Experts Group on Inositol in Basic and Clinical Research (2020) Unfer V 2020 An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs). Expert Opin Drug Metab Toxicol. https://doi.org/10.1080/174252551828344CrossRefPubMed

27.

Dinicola S, Chiu TT, Unfer V, Carlomagno G, Bizzarri M (2014) The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome. J Clin Pharmacol 54:1079–1092. https://doi.org/10.1002/jcph.362CrossRefPubMed

28.

Heimark D, McAllister J, Larner J (2014) Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. Endocr J 61:111–117. https://doi.org/10.1507/endocrj.ej13-0423CrossRefPubMed

29.

Kirchengast S, Huber J (2001) Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum Reprod 16:1255–1260. https://doi.org/10.1093/humrep/16.6.1255CrossRefPubMed

30.

Ezeh U, Pall M, Mathur R, Azziz R (2014) Association of fat to lean mass ratio with metabolic dysfunction in women with polycystic ovary syndrome. Hum Reprod 29:1508–1517. https://doi.org/10.1093/humrep/deu096CrossRefPubMedPubMedCentral

31.

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 24:139–144. https://doi.org/10.1080/09513590801893232CrossRefPubMed

32.

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 7:151–159PubMed

33.

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 13:105–110PubMed

34.

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 23:700–703. https://doi.org/10.1080/09513590701672405CrossRefPubMed

35.

Ikram-u-Allah NS, Qaiser Javed I, Shazia Z, Tayyiba W (2020) Myoinositol in restoring spontaneous ovarian activity in patients with polycystic ovarian syndrome (PCOS). Esculapio. https://doi.org/10.51273/esc20.2516310CrossRef

36.

Kamenov Z, Kolarov G, Gateva A, Carlomagno G, Genazzani AD (2015) Ovulation induction with myo-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance. Gynecol Endocrinol 31:131–135. https://doi.org/10.3109/09513590.2014.964640CrossRefPubMed

37.

Regidor PA, Schindler AE (2016) Myoinositol as a safe and alternative approach in the treatment of infertile PCOS women: a German observational study. Int J Endocrinol. https://doi.org/10.1155/2016/9537632CrossRefPubMedPubMedCentral

38.

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 340:1314–1320. https://doi.org/10.1056/NEJM199904293401703CrossRefPubMed

39.

Iuorno MJ, Jakubowicz DJ, Baillargeon JP, Dillon P, Gunn RD, Allan G, Nestler JE (2002) Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 8:417–423. https://doi.org/10.4158/EP.8.6.417CrossRefPubMed

40.

La Marca A, Grisendi V, Dondi G, Sighinolfi G, Cianci A (2015) The menstrual cycle regularization following D-chiro-inositol treatment in PCOS women: a retrospective study. Gynecol Endocrinol 31:52–56. https://doi.org/10.3109/09513590.2014.964201CrossRefPubMed

41.

Formuso C, Stracquadanio M, Ciotta L (2015) Myo-inositol vs. D-chiro inositol in PCOS treatment. Minerva Ginecol 67:321–325PubMed

42.

Le Donne M, Metro D, Alibrandi A, Papa M, Benvenga S (2019) Effects of three treatment modalities (diet, myoinositol or myoinositol associated with D-chiro-inositol) on clinical and body composition outcomes in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci 23:2293–2301. https://doi.org/10.26355/eurrev_201903_17278CrossRefPubMed

43.

Bevilacqua A, Dragotto J, Giuliani A, Bizzarri M (2019) Myo-inositol and D-chiro-inositol (40:1) reverse histological and functional features of polycystic ovary syndrome in a mouse model. J Cell Physiol 234:9387–9398. https://doi.org/10.1002/jcp.27623CrossRefPubMed

44.

Nordio M, Basciani S, Camajani E (2019) The 40:1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios. Eur Rev Med Pharmacol Sci 23:5512–5521. https://doi.org/10.26355/eurrev_201906_18223CrossRefPubMed

45.

Kishan C, Sujata M, Sandhya B (2017) A randomised clinical trial comparing myoinositol and metformin in PCOS. Int J Reprod Contracept Obstet Gynecol 6:1814–1820. https://doi.org/10.18203/2320-1770.ijrcog20171563CrossRef

46.

Chhabra N, Malik S (2018) Effect of insulin sensitizers on raised serum anti-mullerian hormone levels in infertile women with polycystic ovarian syndrome. J Hum Reprod Sci 11:348–352. https://doi.org/10.4103/jhrs.JHRS_59_17CrossRefPubMedPubMedCentral

47.

Angik R, Jajoo SS, Hariharan C, Chimote A (2015) A comparative study of metabolic and hormonal effects of myoinositol vs. metformin in women with polycystic ovary syndrome: a randomised controlled trial. Int J Reprod Contracept Obstet Gynecol. https://doi.org/10.5455/2320-1770.ijrcog20150234CrossRef

48.

Pourghasem S, Bazarganipour F, Taghavi SA et al (2019) The effectiveness of inositol and metformin on infertile polycystic ovary syndrome women with resistant to letrozole. Arch Gynecol Obstet 299:1193–1199. https://doi.org/10.1007/s.00404-029-05064-5CrossRefPubMed

49.

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 26:275–280. https://doi.org/10.3109/09513590903366996CrossRefPubMed

50.

Fruzzetti F, Perini D, Russo M, Bucci F, Gadducci A (2017) Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS). Gynecol Endocrinol 33:39–42. https://doi.org/10.1080/09513590.2016.1236078CrossRefPubMed

51.

Bahadur A, Arora H, Ravi AK, Naithani M, Bahurupi Y, Chaturvedi J, Ajmani M, Mundhra R (2021) Comparison of clinical metabolic and hormonal effects of metformin versus, combined therapy of metformin with Myoinositol plus d-Chiro-inositol in women with polycystic ovary syndrome (pcos): a randomized controlled trial. Cureus. https://doi.org/10.7759/cureus.15510CrossRefPubMedPubMedCentral

52.

Nazirudeen R, Sridhar S, Priyanka R, Sumathi B, Natarajan V, Subbiah E, Raghavan KS, Sangumani J (2023) A randomized controlled trial comparing myoinositol with metformin versus metformin monotherapy in polycystic ovary syndrome. Clin Endocrinol (Oxf) 99(2):198–205. https://doi.org/10.1111/cen.14931CrossRefPubMed

53.

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 18:408–416. https://doi.org/10.1093/humrep/deg113CrossRefPubMed

54.

Teede HJ, Tay CT, Laven J, Dokras A, Moran LJ, Piltonen TT, Costello MF, Boivin J, Redman LM, Boyle JA, Norman RJ, Mousa A, Joham AE, International PCOS Network (2023) Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. Eur J Endocrinol 189(2):G43–G64. https://doi.org/10.1093/ejendo/lvad096CrossRefPubMed

55.

Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, Santis De (2009) Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles, A prospective, controlled, randomized trial. Fertil Steril 91(5):1750–1754. https://doi.org/10.1016/j.fertnstert.2008.01.088CrossRefPubMed

56.

Ciotta L, Stracquadanio M, Pagano I, Carbonaro A, Palumbo M, Gulino M (2011) Effects of myo-inositol supplementation on oocyte’s quality in PCOS patients: a double blind trial. Eur Rev Med Pharmacol Sci 15(5):509–514PubMed

57.

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 stud Gynecol Endocrinol 29(4):375–379. https://doi.org/10.3109/09513590.2012.743020CrossRef

58.

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(1):69–73. https://doi.org/10.3109/09513590.2015.1101444.60CrossRefPubMed

59.

Showell MG, Mackenzie-Proctor R, Jordan V, Hodgson R, Farquhar C (2018) Inositol for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD012378.pub2CrossRefPubMedPubMedCentral

60.

Mendoza N, Perez L, Simoncini T, Genazzani A (2017) Inositol supplementation in women with polycystic ovary syndrome undergoing intracytoplasmatic 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.2017.07.005CrossRefPubMed

61.

Laganà AS, Vitagliano A, Noventa M, Ambrosini G, D’Anna R (2018) 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(4):675–684. https://doi.org/10.1007/s00404-018-4861-yCrossRefPubMed

62.

Bhide P, Jyotsna P, Anil G, Amit S, Roy H, Ganesh A (2019) Effect of myo-inositol/di-chiro-inositol on markers of ovarian reserve in women with PCOS undergoing IVF/ICSI: A systematic review and meta-analysis. Acta Obstet Gynecol Scand 98(10):1235–1244. https://doi.org/10.1111/aogs.13625CrossRefPubMed

63.

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/10.1186/1477-7827-10-52CrossRefPubMedPubMedCentral

64.

Schillaci R, Mangione D, Lo Monte G, Vassiliadis A (2012) Inositol supplementation and IVF outcome: preliminary data. J Gynaecol Obstet 24(1):38–44

65.

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). https://doi.org/10.1097/MD.0000000000008842CrossRefPubMedPubMedCentral

66.

Brusco GF, Mariani M (2013) Inositol: effects on oocyte quality in patients undergoing ICSI. an open study. Eur Rev Med Pharmacol Sci 17:3095–3102 (PMID: 24302192)PubMed

67.

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 Re 8:37. https://doi.org/10.1186/s13048-015-0167-xCrossRef

68.

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):452–457PubMed

69.

Greff D, Juhász AE, Váncsa S, Váradi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirády P, Ács N, Várbíró S, Horváth EM (2023) Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol 21(1):10. https://doi.org/10.1186/s12958-023-01055-zCrossRefPubMedPubMedCentral

70.

Lain KY, Catalano PM (2007) Metabolic changes in pregnancy. Clin Obstet Gynecol 50(4):938–948. https://doi.org/10.1097/GRF.0b013e31815a5494CrossRefPubMed

71.

Buchanan TA, Xiang AH (2005) Gestational diabetes mellitus. J Clin Invest 115(3):485–491. https://doi.org/10.1172/JCI24531CrossRefPubMedPubMedCentral

72.

Catalano PM, McIntyre HD, Cruickshank JK, McCance DR, Dyer AR, Metzger BE, Lowe LP, Trimble ER, Coustan DR, Hadden DR, Persson B, Hod M, Oats JJN (2012) The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes. Diabetes Care 35(4):780–786. https://doi.org/10.2337/dc11-1790CrossRefPubMedPubMedCentral

73.

Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L (2013) Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. preventive services task force and the national institutes of health office of medical applications of research. Ann Intern Med 159:123–129. https://doi.org/10.7326/0003-4819-159-2-201307160-00661CrossRefPubMed

74.

D’Anna R, Scilipoti A, Giordano D, Caruso C, Cannata ML, Interdonato ML, Corrado F, Di Benedetto A (2013) Myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. Diabetes Care 36:854–857. https://doi.org/10.2337/dc12-1371CrossRefPubMedPubMedCentral

75.

Matarrelli B, Vitacolonna E, D’Angelo M, Pavone G, Mattei PA, Liberati M, Celentano C (2013) Effect of dietary myo-inositol supplementation in pregnancy on the incidence of maternal gestational diabetes mellitus and fetal outcomes: a randomized controlled trial. J Matern Fetal Neonatal Med 26(10):967–972. https://doi.org/10.3109/14767058.2013.766691CrossRefPubMed

76.

Malvasi A, Casciaro F, Minervini MM, Kosmas I, Mynbaev OA, Pacella E, Monti Condesnitt V, Creanza A, Di Renzo GC, Tinelli A (2014) Myo-inositol, D-chiro-inositol, folic acid and manganese in second trimester of pregnancy: a preliminary investigation. Eur Rev Med Pharmacol Sci 18(2):270–274 (PMID: 24488919)PubMed

77.

D’Anna R, Di Benedetto A, Scilipoti A, Santamaria A, Interdonato ML, Petrella E, Neri I, Pintaudi B, Corrado F, Facchinetti F (2015) Myo-inositol supplementation for prevention of gestational diabetes in obese pregnant women: a randomized controlled trial. Obstet Gynecol 126:310–315. https://doi.org/10.1097/AOG.0000000000000958CrossRefPubMed

78.

Santamaria A, Di Benedetto A, Petrella E, Pintaudi B, Corrado F, D’Anna R, Neri I, Facchinetti F (2016) Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial. J Matern Fetal Neonatal Med 29(19):3234–3237. https://doi.org/10.3109/14767058.2015.1121478CrossRefPubMed

79.

Farren M, Daly N, McKeating A, Kinsley B, Turner MJ, Daly S (2017) The Prevention of gestational diabetes mellitus with antenatal oral inositol supplementation: a randomized controlled trial. Diabetes Care 40(6):759–763. https://doi.org/10.2337/dc16-2449CrossRefPubMed

80.

Celentano C, Matarrelli B, Pavone G, Vitacolonna E, Mattei PA, Berghella V, Liberati M (2020) The influence of different inositol stereoisomers supplementation in pregnancy on maternal gestational diabetes mellitus and fetal outcomes in high-risk patients: a randomized controlled trial. J Matern Fetal Neonatal Med 33(5):743–751. https://doi.org/10.1080/14767058.2018.1500545CrossRefPubMed

81.

Vitale SG, Corrado F, Caruso S, Di Benedetto A, Giunta L, Cianci A, D’Anna R (2021) Myo-inositol supplementation to prevent gestational diabetes in overweight non-obese women: bioelectrical impedance analysis, metabolic aspects, obstetric and neonatal outcomes - a randomized and open-label, placebo-controlled clinical trial. Int J Food Sci Nutr 72(5):670–679. https://doi.org/10.1080/09637486.2020.1852191CrossRefPubMed

82.

Godfrey KM, Barton SJ, El-Heis S, Kenealy T, Nield H, Baker PN, Chong YS, Cutfield W, Chan SY, NiPPeR Study Group (2021) Myo-inositol, probiotics, and micronutrient supplementation from preconception for glycemia in pregnancy: NiPPeR international multicenter double-blind randomized controlled trial. Diabetes Care 44(5):1091–1099. https://doi.org/10.2337/dc20-2515CrossRefPubMedPubMedCentral

83.

Chan SY, Yong HEJ, Chang HF, Barton SJ, Galani S, Zhang H, Wong JT, Ong J, Ebreo M, El-Heis S, Kenealy T, Nield H, Baker PN, Chong YS, Cutfield WS, Godfrey KM, NiPPeR Study Group (2022) Peripartum outcomes after combined myo-inositol, probiotics, and micronutrient supplementation from preconception: the NiPPeR randomized controlled trial. Am J Obstet Gynecol MFM. https://doi.org/10.1016/j.ajogmf.2022.100714CrossRefPubMedPubMedCentral

84.

Amaefule CE, Drymoussi Z, Gonzalez Carreras FJ, Pardo Llorente MDC, Lanz D, Dodds J, Sweeney L, Pizzo E, Thomas A, Heighway J, Daru J, Sobhy S, Poston L, Khalil A, Myers J, Harden A, Hitman G, Khan KS, Zamora J, Pérez T, Huda MSB, Thangaratinam S (2022) Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study. BMJ Open. https://doi.org/10.1136/bmjopen-2021-050110CrossRefPubMedPubMedCentral

85.

Esmaeilzadeh S, Ghadimi R, Mashayekh-Amiri S, Delavar MA, Basirat Z (2023) The effect of myo-inositol supplementation on the prevention of gestational diabetes in overweight pregnant women: a randomized, double-blind, controlled trial. Minerva Obstet Gynecol 75(4):357–364. https://doi.org/10.23736/S2724-606X.22.05036-9CrossRefPubMed

86.

Dell’Edera D, Sarlo F, Allegretti A, Simone F, Lupo MG, Epifania AA (2017) The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance. Biomed Rep 7(2):169–172. https://doi.org/10.3892/br.2017.939CrossRefPubMedPubMedCentral

87.

Dell’Edera D, Sarlo F, Allegretti A, Epifania AA, Simone F, Lupo MG, Benedetto M, D’Apice MR, Capalbo A (2017) Prevention of neural tube defects and maternal gestational diabetes through the inositol supplementation: preliminary results. Eur Rev Med Pharmacol Sci 21(14):3305–3311 (PMID: 28770950)PubMed

88.

D’Anna R, Di Benedetto V, Rizzo P, Raffone E, Interdonato ML, Corrado F, Di Benedetto A (2012) Myo-inositol may prevent gestational diabetes in PCOS women. Gynecol Endocrinol 28(6):440–442. https://doi.org/10.3109/09513590.2011.633665CrossRefPubMed

89.

Santamaria A, Alibrandi A, Di Benedetto A, Pintaudi B, Corrado F, Facchinetti F, D’Anna R (2018) Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: a secondary analysis from 3 RCTs. Am J Obstet Gynecol 219(3):300.e1-300.e6. https://doi.org/10.1016/j.ajog.2018.05.018CrossRefPubMed

90.

Corrado F, D’Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, Di Benedetto A (2011) The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med 28(8):972–975. https://doi.org/10.1111/j.1464-5491.2011.03284.xCrossRefPubMed

91.

Fraticelli F, Celentano C, Zecca IA, Di Vieste G, Pintaudi B, Liberati M, Franzago M, Di Nicola M, Vitacolonna E (2018) Effect of inositol stereoisomers at different dosages in gestational diabetes: an open-label, parallel, randomized controlled trial. Acta Diabetol 55:805–812. https://doi.org/10.1007/s00592-018-1157-4CrossRefPubMed

92.

D’Anna R, Corrado F, Loddo S, Gullo G, Giunta L, Di Benedetto A (2021) Myoinositol plus α-lactalbumin supplementation, insulin resistance and birth outcomes in women with gestational diabetes mellitus: a randomized, controlled study. Sci Rep 11(1):8866. https://doi.org/10.1038/s41598-021-88329-xCrossRefPubMedPubMedCentral

93.

Kulshrestha V, Balani S, Kachhawa G, Vanamail P, Kumari R, Sharma JB, Bhatla N (2021) Efficacy of myoinositol in treatment of gestational diabetes mellitus in Asian Indian women: a pilot randomized clinical trial. Eur J Obstet Gynecol Reprod Biol 260:42–47. https://doi.org/10.1016/j.ejogrb.2021.02.017CrossRefPubMed

94.

Cavalli P, Ronda E (2017) Myoinositol: the bridge (ponti) to reach a healthy pregnancy. Int J Endocrinol 2017:5846286. https://doi.org/10.1155/2017/5846286CrossRefPubMedPubMedCentral

95.

Cogram P, Tesh S, Tesh J, Wade A, Allan G, Greene ND, Copp AJ (2002) D-chiro-inositol is more effective than myo-inositol in preventing folate-resistant mouse neural tube defects. Hum Reprod 17:2451–2458. https://doi.org/10.1093/humrep/17.9.2451CrossRefPubMed

96.

Facchinetti F, Cavalli P, Copp AJ, D’Anna R, Kandaraki E, Greene NDE, Unfer V, Experts Group on Inositol in Basic and Clinical Research (2020) An update on the use of inositols in preventing gestational diabetes mellitus (GDM) and neural tube defects (NTDs). Expert Opin Drug Metab Toxicol 16(12):1187–1198. https://doi.org/10.1080/17425255.2020.1828344CrossRefPubMed

97.

Groenen PM, Peer PG, Wevers RA, Swinkels DW, Franke B, Mariman EC, Steegers-Theunissen RP (2003) Maternal myo-inositol, glucose, and zinc status is associated with the risk of offspring with Spina bifida. Am J Obstet Gynecol 189:1713–1719. https://doi.org/10.1016/s0002-9378(03)00807-xCrossRefPubMed

98.

Hendricks KA, Nuno OM, Suarez L, Larsen R (2001) Effects of hyperinsulinemia and obesity on risk of neural tube defects among Mexican Americans. Epidemiology 12:630–635. https://doi.org/10.1097/00001648-200111000-00009CrossRefPubMed

99.

Reece EA, Khandelwal M, Wu YK, Borenstein M (1997) Dietary intake of myo-inositol and neural tube defects in offspring of diabetic rats. Am J Obstet Gynecol 176(3):536–539. https://doi.org/10.1016/s0002-9378(97)70543-xCrossRefPubMed

100.

Goldman AS, Goto MP (1991) Biochemical basis of the diabetic embryopathy. Isr J Med Sci 27(8–9):469–477PubMed

101.

Cavalli P, Tedoldi S, Riboli B (2008) Inositol supplementation in pregnancies at risk of apparently folate-resistant NTDs. Birth Defects Res A Clin Mol Teratol 82:540–542. https://doi.org/10.1002/bdra.20454CrossRefPubMed

102.

Cavalli P, Tonni G, Grosso E, Poggiani C (2011) Effects of inositol supplementation in a cohort of mothers at risk of producing an NTD pregnancy. Birth Defects Res A Clin Mol Teratol 91(11):962–965. https://doi.org/10.1002/bdra.22853CrossRefPubMed

103.

Greene ND, Leung K-Y, Gay V, Burren K, Mills K, Chitty LS, Copp AJ (2016) Inositol for the prevention of neural tube defects: a pilot randomised controlled trial. Br J Nutr 115:974–983. https://doi.org/10.1017/S0007114515005322CrossRefPubMedPubMedCentral

Title: Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)—Women’s Endocrinology
Authors: Costanzo Moretti
Marco Bonomi
Paola Dionese
Silvia Federici
Anna Maria Fulghesu
Jacopo Giannelli
Roberta Giordano
Laura Guccione
Elisa Maseroli
Paolo Moghetti
Roberto Mioni
Rosario Pivonello
Chiara Sabbadin
Carla Scaroni
Massimo Tonacchera
Nunzia Verde
Linda Vignozzi
Alessandra Gambineri
Publication date: 15-07-2024
Publisher: Springer International Publishing
Keywords: Endocrinology and Reproductive Medicine
Polycystic Ovary Syndrome
Fertility
Gestational Diabetes
Pregnancy
Menstrual and Ovulation Disorder
Neonatology
Infertility
Polycystic Ovary Syndrome
Gestational Diabetes
Published in: Journal of Endocrinological Investigation / Issue 9/2024
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-024-02363-w

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Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)—Women’s Endocrinology

Abstract

Purpose

Methods

Results

Conclusion

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Abstract

Purpose

Methods

Results

Conclusion

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