An innovative approach to polycystic ovary syndrome

References

• Artini PG, Casarosa E, Carletti E, Monteleone P, Di Noia A, Di Berardino OM. 2017. In vitro effect of myo-inositol on sperm motility in normal and oligoasthenospermia patients undergoing in vitro fertilization. Gynecological Endocrinology 33:109–112.
   PubMed Web of Science ®Google Scholar
• Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE, Jr., Apridonidze T, Iuorno MJ, Nestler JE. 2006. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care 29:300–305.
   PubMed Web of Science ®Google Scholar
• Barbaro D, Orru B, Unfer V. 2019. Iodine and Myo-Inositol: a novel promising combination for iodine deficiency. Frontiers in Endocrinology 10:457.
   PubMed Web of Science ®Google Scholar
• Bevilacqua A, Bizzarri M. 2018. Inositols in insulin signaling and glucose metabolism. International Journal of Endocrinology 2018:1968450.
   PubMed Web of Science ®Google Scholar
• Bevilacqua A, Carlomagno G, Gerli S, Montanino Oliva M, Devroey P, Lanzone A, et al. 2015. Results from the International Consensus Conference on myo-inositol and D-chiro-inositol in Obstetrics and Gynecology–assisted reproduction technology. Gynecological Endocrinology 31:441–446.
   PubMed Web of Science ®Google Scholar
• 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. Journal of Cellular Physiology 234:9387–9398.
   PubMed Web of Science ®Google Scholar
• Bizzarri M, Fuso A, Dinicola S, Cucina A, Bevilacqua A. 2016. Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opinion on Drug Metabolism & Toxicology 12:1181–1196.
   PubMed Web of Science ®Google Scholar
• Burghen GA, Givens JR, Kitabchi AE. 1980. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. The Journal of Clinical Endocrinology and Metabolism 50:113–116.
   PubMed Web of Science ®Google Scholar
• Calogero AE, Gullo G, La Vignera S, Condorelli RA, Vaiarelli A. 2015. Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study. Andrology 3:491–495.
   PubMed Web of Science ®Google Scholar
• Carlomagno G, De Grazia S, Unfer V, Manna F. 2012. Myo-inositol in a new pharmaceutical form: a step forward to a broader clinical use. Expert Opinion on Drug Delivery 9:267–271.
   PubMed Web of Science ®Google Scholar
• Carlomagno G, Minini M, Tilotta M, Unfer V. 2018. From Implantation to Birth: Insight into Molecular Melatonin Functions. International Journal of Molecular Sciences. 19:2802.
   PubMed Web of Science ®Google Scholar
• Carlomagno G, Nordio M, Chiu TT, Unfer V. 2011a. Contribution of myo-inositol and melatonin to human reproduction. European Journal of Obstetrics, Gynecology, and Reproductive Biology 159:267–272.
   PubMed Web of Science ®Google Scholar
• Carlomagno G, Unfer V. 2011. Inositol safety: clinical evidences. European Review for Medical and Pharmacological Sciences 15:931–936.
   PubMed Web of Science ®Google Scholar
• Carlomagno G, Unfer V, Roseff S. 2011b. The D-chiro-inositol paradox in the ovary. Fertility and Sterility 95:2515–2516.
   PubMed Web of Science ®Google Scholar
• Celentano C, Matarrelli B, Pavone G, Vitacolonna E, Mattei PA, Berghella V, et al. 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. The Journal of Maternal-Fetal & Neonatal Medicine 33:743–751.
   PubMedGoogle Scholar
• Chatree S, Thongmaen N, Tantivejkul K, Sitticharoon C, Vucenik I. 2020. Role of inositols and inositol phosphates in energy metabolism. Molecules 25:5079.
   PubMed Web of Science ®Google Scholar
• Chauvin TR, Griswold MD. 2004. Characterization of the expression and regulation of genes necessary for myo-inositol biosynthesis and transport in the seminiferous epithelium. Biology of Reproduction 70:744–751.
   PubMed Web of Science ®Google Scholar
• Cheang KI, Baillargeon JP, Essah PA, Ostlund RE, Jr., Apridonize T, Islam L, et al. 2008. Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome. Metabolism 57:1390–1397.
   PubMed Web of Science ®Google Scholar
• 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. Human Reproduction 18:408–416.
   PubMed Web of Science ®Google Scholar
• 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. Human Reproduction 17:1591–1596.
   PubMed Web of Science ®Google Scholar
• 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. Journal of Assisted Reproduction and Genetics 9:524–530.
   PubMed Web of Science ®Google Scholar
• Colone M, Calcabrini A, Unfer V, Stringaro A. 2017. Contribution of electron microscopy to study in vitro inositol effects on human spermatozoa. European Review for Medical and Pharmacological Sciences 21:4–9.
   PubMed Web of Science ®Google Scholar
• Colone M, Marelli G, Unfer V, Bozzuto G, Molinari A, Stringaro A. 2010. Inositol activity in oligoasthenoteratospermia–an in vitro study. European Review for Medical and Pharmacological Sciences 14:891–896.
   PubMed Web of Science ®Google Scholar
• Colonese F, Lagana AS, Colonese E, Sofo V, Salmeri FM, Granese R, et al. 2015. The pleiotropic effects of vitamin D in gynaecological and obstetric diseases: an overview on a hot topic. BioMed Research International 2015:986281.
   PubMed Web of Science ®Google Scholar
• Condorelli RA, La Vignera S, Bellanca S, Vicari E, Calogero AE. 2012. Myoinositol: does it improve sperm mitochondrial function and sperm motility? Urology 79:1290–1295.
   PubMed Web of Science ®Google Scholar
• Condorelli RA, La Vignera S, Di Bari F, Unfer V, Calogero AE. 2011. Effects of myoinositol on sperm mitochondrial function in-vitro. European Review for Medical and Pharmacological Sciences 15:129–134.
   PubMed Web of Science ®Google Scholar
• Condorelli RA, La Vignera S, Mongioi LM, Vitale SG, Lagana AS, Cimino L, et al. 2017. Myo-inositol as a male fertility molecule: speed them up. European Review for Medical and Pharmacological Sciences 21:30–35.
   PubMed Web of Science ®Google Scholar
• Correia J, Michelangeli F, Publicover S. 2015. Regulation and roles of Ca2+ stores in human sperm. Reproduction 150:R65–76.
   PubMed Web of Science ®Google Scholar
• Costabile L, Unfer V. 2017. Treatment of gestational diabetes mellitus with myo-inositol: analyzing the cutting edge starting from a peculiar case. European Review for Medical and Pharmacological Sciences 21:73–76.
   PubMed Web of Science ®Google Scholar
• 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. European Review for Medical and Pharmacological Sciences. 13:105–110.
   PubMed Web of Science ®Google Scholar
• Costantino M, Guaraldi C, Costantino D. 2016. Resolution of subchorionic hematoma and symptoms of threatened miscarriage using vaginal alpha lipoic acid or progesterone: clinical evidences. European Review for Medical and Pharmacological Sciences 20:1656–1663.
   PubMed Web of Science ®Google Scholar
• Costantino M, Guaraldi C, Costantino D, De Grazia S, Unfer V. 2014. Peripheral neuropathy in obstetrics: efficacy and safety of alpha-lipoic acid supplementation. European Review for Medical and Pharmacological Sciences 18:2766–2771.
   PubMed Web of Science ®Google Scholar
• Cotrozzi G, Matteini M, Relli P, Lazzari T. 1983. Hyperinsulinism and insulin resistance in polycystic ovarian syndrome: a verification using oral glucose, I.V. Glucose and tolbutamide. Acta Diabetologica Latina 20:135–142.
   PubMedGoogle Scholar
• Croze ML, Soulage CO. 2013. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie 95:1811–1827.
   PubMed Web of Science ®Google Scholar
• De Grazia S, Carlomagno G, Unfer V, Cavalli P. 2012. Myo-inositol soft gel capsules may prevent the risk of coffee-induced neural tube defects. Expert Opinion on Drug Delivery 9:1033–1039.
   PubMed Web of Science ®Google Scholar
• 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. Journal of Clinical Pharmacology 54:1079–1092.
   PubMed Web of Science ®Google Scholar
• Dinkova A, Martinov D, Konova E. 2017. Efficacy of myo-inositol in the clinical management of patients with asthenozoospermia. European Review for Medical and Pharmacological Sciences 21:62–65.
   PubMed Web of Science ®Google Scholar
• Eisenberg F, Jr., Bolden AH. 1964. Reproductive tract as site of synthesis and secretion of inositol in the male rat. Nature 202:599–600.
   PubMed Web of Science ®Google Scholar
• Facchinetti F, Appetecchia M, Aragona C, Bevilacqua A, Bezerra Espinola MS, Bizzarri M, et al. 2020. Experts’ opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond. Expert Opinion on Drug Metabolism & Toxicology 16:255–274.
   PubMed Web of Science ®Google Scholar
• Facchinetti F, Bizzarri M, Benvenga S, D’Anna R, Lanzone A, Soulage C, et al. 2015. Results from the International Consensus Conference on Myo-inositol and d-chiro-inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS. European Journal of Obstetrics & Gynecology and Reproductive Biology 195:72–76.
   PubMed Web of Science ®Google Scholar
• Facchinetti F, Orru B, Grandi G, Unfer V. 2019. Short-term effects of metformin and myo-inositol in women with polycystic ovarian syndrome (PCOS): a meta-analysis of randomized clinical trials. Gynecological Endocrinology 35:198–206.
   PubMed Web of Science ®Google Scholar
• Facchinetti FDG, Neri I. 2016. The Ratio of MI to DCI and Its Impact in the Treatment of Polycystic Ovary Syndrome: Experimental and Literature Evidences. Frontiers in Gynecological Endocrinology 3:103–109.
   Google Scholar
• FDA. 2017. Opinion: Inositol [Online]; [cited 2021 Apr 21]. Available from: http://wayback.archive-it.org/7993/20171031060738/https://www.fda.gov/Food/IngredientsPackagingLabeling/GRAS/SCOGS/ucm260436.htm.
   Google Scholar
• Fraticelli F, Celentano C, Zecca IA, Di Vieste G, Pintaudi B, Liberati M, et al. 2018. Effect of inositol stereoisomers at different dosages in gestational diabetes: an open-label, parallel, randomized controlled trial. Acta Diabetologica 55:805–812.
   PubMed Web of Science ®Google Scholar
• Garzon S, Lagana AS, Monastra G. 2019. Risk of reduced intestinal absorption of myo-inositol caused by D-chiro-inositol or by glucose transporter inhibitors. Expert Opinion on Drug Metabolism & Toxicology. 15:697–703.
   PubMed Web of Science ®Google Scholar
• Gateva A, Unfer V, Kamenov Z. 2018. The use of inositol(s) isomers in the management of polycystic ovary syndrome: a comprehensive review. Gynecological Endocrinology 34:545–550.
   PubMed Web of Science ®Google Scholar
• 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. Gynecological Endocrinology 24:139–144.
   PubMed Web of Science ®Google Scholar
• 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. European Review for Medical and Pharmacological Sciences. 7:151–159.
   PubMedGoogle Scholar
• 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. European Review for Medical and Pharmacological Sciences. 11:347–354.
   PubMed Web of Science ®Google Scholar
• Ghafoorunissa   1975. Effect of dietary protein on the biosynthesis of inositol in rat testes. Reproduction, Fertility and Development 42:233–238.
   Google Scholar
• Gulino FA, Leonardi E, Marilli I, Musmeci G, Vitale SG, Leanza V, et al. 2016. Effect of treatment with myo-inositol on semen parameters of patients undergoing an IVF cycle: in vivo study. Gynecological Endocrinology 32:65–68.
   PubMed Web of Science ®Google Scholar
• 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. Endocrine Journal 61:111–117.
   PubMed Web of Science ®Google Scholar
• Hinton BT, Setchell BP. 1981. Micropuncture and microanalytical studies of rhesus monkey and baboon epididymis and the human ductus deferens. American Journal of Primatology 1:251–256.
   PubMed Web of Science ®Google Scholar
• 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 132:652–657.
   PubMed Web of Science ®Google Scholar
• Iuorno MJ, Jakubowicz DJ, Baillargeon JP, Dillon P, Gunn RD, Allan G, et al. 2002. Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocrine Practice 8:417–423.
   PubMedGoogle Scholar
• 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. Gynecological Endocrinology 31:131–135.
   PubMed Web of Science ®Google Scholar
• Kumar N, Singh AK. 2015. Trends of male factor infertility, an important cause of infertility: a review of literature. Journal of Human Reproductive Sciences 8:191–196.
   PubMedGoogle Scholar
• Lackey KH, Pope PM, Johnson MD. 2003. Expression of 1L-myoinositol-1-phosphate synthase in organelles. Plant Physiology 132:2240–2247.
   PubMed Web of Science ®Google Scholar
• Lagana AS, Barbaro L, Pizzo A. 2015. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment with D-Chiro-Inositol. Archives of Gynecology and Obstetrics 291:1181–1186.
   PubMed Web of Science ®Google Scholar
• Lagana AS, Garzon S, Casarin J, Franchi M, Ghezzi F. 2018a. Inositol in polycystic ovary syndrome: restoring fertility through a pathophysiology-based approach. Trends in Endocrinology and Metabolism. 29:768–780.
   PubMed Web of Science ®Google Scholar
• Lagana AS, Pizzo A. 2015. Authors’ reply to: “Empiric” inositol supplementation in normal-weight non-insulin resistant women with polycystic ovarian disease: from the absence of benefit to the potential adverse effects. Archives of Gynecology and Obstetrics 291:959–960.
   PubMed Web of Science ®Google Scholar
• Lagana AS, Rossetti P, Buscema M, La Vignera S, Condorelli RA, Gullo G, et al. 2016. Metabolism and Ovarian function in PCOS women: a therapeutic approach with inositols. International Journal of Endocrinology. 2016:1–9.
   Web of Science ®Google Scholar
• Lagana AS, Rossetti P, Sapia F, Chiofalo B, Buscema M, Valenti G, et al. 2017. Evidence-based and patient-oriented inositol treatment in polycystic ovary syndrome: changing the perspective of the disease. International Journal of Endocrinology and Metabolism 15:e43695.
   PubMed Web of Science ®Google Scholar
• Lagana AS, Unfer V. 2019. D-Chiro-Inositol’s action as aromatase inhibitor: rationale and potential clinical targets. European Review for Medical and Pharmacological Sciences. 23:10575–10576.
   PubMed Web of Science ®Google Scholar
• Laganà AS, Vitagliano A, Noventa M, Ambrosini G, D’Anna R. 2018b. 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. Archives of Gynecology and Obstetrics 298:675–684.
   PubMed Web of Science ®Google Scholar
• Larner J, Allan G, Kessler C, Reamer P, Gunn R, Huang LC. 1998. Phosphoinositol glycan derived mediators and insulin resistance. Prospects for diagnosis and therapy. Journal of Basic and Clinical Physiology and Pharmacology 9:127–137.
   PubMedGoogle Scholar
• Larner J, Huang LC, Tang G, Suzuki S, Schwartz CFW, Romero G, et al. 1988. Insulin mediators: structure and formation. Cold Spring Harbor Symposia on Quantitative Biology 53: 965–971.
   PubMedGoogle Scholar
• Lemmer HJ, Hamman JH. 2013. Paracellular drug absorption enhancement through tight junction modulation. Expert Opinion on Drug Delivery 10:103–114.
   PubMed Web of Science ®Google Scholar
• Leung KY, Mills K, Burren KA, Copp AJ, Greene ND. 2011. Quantitative analysis of myo-inositol in urine, blood and nutritional supplements by high-performance liquid chromatography tandem mass spectrometry. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 879:2759–2763.
   PubMed Web of Science ®Google Scholar
• Lewin LM, Yannai Y, Melmed S, Weiss M. 1982. myo-inositol in the reproductive tract of the female rat. The International Journal of Biochemistry 14:147–150.
   PubMedGoogle Scholar
• Maffucci T, Falasca M. 2020. Signalling properties of inositol polyphosphates. Molecules 25:5281.
   PubMed Web of Science ®Google Scholar
• Milewska EM, Czyzyk A, Meczekalski B, Genazzani AD. 2016. Inositol and human reproduction. From cellular metabolism to clinical use. Gynecological Endocrinology 32:690–695.
   PubMed Web of Science ®Google Scholar
• 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. Gynecological Endocrinology 27:920–924.
   PubMed Web of Science ®Google Scholar
• Minozzi M, D’Andrea G, Unfer V. 2008. Treatment of hirsutism with myo-inositol: a prospective clinical study. Reproductive Biomedicine Online 17:579–582.
   PubMed Web of Science ®Google Scholar
• Monastra G, De Grazia S, Cilaker Micili S, Goker A, Unfer V. 2016. Immunomodulatory activities of alpha lipoic acid with a special focus on its efficacy in preventing miscarriage. Expert Opinion on Drug Delivery 13:1695–1708.
   PubMed Web of Science ®Google Scholar
• Monastra G, De Grazia S, De Luca L, Vittorio S, Unfer V. 2018a. Vitamin D: a steroid hormone with progesterone-like activity. European Review for Medical and Pharmacological Sciences 22:2502–2512.
   PubMed Web of Science ®Google Scholar
• Monastra G, Sambuy Y, Ferruzza S, Ferrari D, Ranaldi G. 2018b. Alpha-lactalbumin effect on Myo-inositol intestinal absorption: in vivo and in vitro. Current Drug Delivery 15:1305–1311.
   PubMed Web of Science ®Google Scholar
• Monastra G, Unfer V, Harrath AH, Bizzarri M. 2017. Combining treatment with myo-inositol and D-chiro-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients. Gynecological Endocrinology 33:1–9.
   PubMed Web of Science ®Google Scholar
• Montanino Oliva M, Buonomo G, Calcagno M, Unfer V. 2018. Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women. Journal of Ovarian Research 11:38.
   PubMed Web of Science ®Google Scholar
• Montanino Oliva M, Minutolo E, Lippa A, Iaconianni P, Vaiarelli A. 2016. Effect of myoinositol and antioxidants on sperm quality in men with metabolic syndrome. International Journal of Endocrinology 2016:1674950.
   PubMed Web of Science ®Google Scholar
• Morris RN, Collins AC. 1971. Biosynthesis of myo-inositol by rat testis following surgically induced cryptorchidism or treatment with triethylenemelamine. Journal of Reproduction and Fertility 27:201–210.
   PubMedGoogle Scholar
• Muscogiuri G, Palomba S, Lagana AS, Orio F. 2016a. Current insights into inositol isoforms, mediterranean and ketogenic diets for polycystic ovary syndrome: from bench to bedside. Current Pharmaceutical Design 22:5554–5557.
   PubMed Web of Science ®Google Scholar
• Muscogiuri G, Palomba S, Lagana AS, Orio F. 2016b. Inositols in the treatment of insulin-mediated diseases. International Journal of Endocrinology 2016:1–1.
   Web of Science ®Google Scholar
• Nestler JE, Jakubowicz DJ, de Vargas AF, Brik C, Quintero N, Medina F. 1998. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. The Journal of Clinical Endocrinology and Metabolism 83:2001–2005.
   PubMed Web of Science ®Google Scholar
• Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. 1999. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. New England Journal of Medicine 340:1314–1320.
   PubMed Web of Science ®Google Scholar
• Nestler JE, Unfer V. 2015. Reflections on inositol(s) for PCOS therapy: steps toward success. Gynecological Endocrinology 31:501–505.
   PubMed Web of Science ®Google Scholar
• 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. European Review for Medical and Pharmacological Sciences 23:5512–5521.
   PubMed Web of Science ®Google Scholar
• Pak Y, Huang LC, Lilley KJ, Larner J. 1992. In vivo conversion of [3H]myoinositol to [3H]chiroinositol in rat tissues. Journal of Biological Chemistry. 267:16904–16910.
   PubMed Web of Science ®Google Scholar
• Palmieri M, Papale P, Della Ragione A, Quaranta G, Russo G, Russo S. 2016. In vitro antioxidant treatment of semen samples in assisted reproductive technology: effects of Myo-inositol on nemaspermic parameters. International Journal of Endocrinology. 2016:1–5.
   Web of Science ®Google Scholar
• Papaleo E, Unfer V, Baillargeon JP, Chiu TT. 2009a. Contribution of myo-inositol to reproduction. European Journal of Obstetrics, Gynecology, and Reproductive Biology 147:120–123.
   PubMed Web of Science ®Google Scholar
• Papaleo E, Unfer V, Baillargeon JP, De Santis L, Fusi F, Brigante C, et al. 2007. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecological Endocrinology 23:700–703.
   PubMed Web of Science ®Google Scholar
• Papaleo E, Unfer V, Baillargeon JP, Fusi F, Occhi F, De Santis L. 2009b. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles: a prospective, controlled, randomized trial. Fertility and Sterility 91:1750–1754.
   PubMed Web of Science ®Google Scholar
• Parente E, Colannino G, Picconi O, Monastra G. 2017. Safety of oral alpha-lipoic acid treatment in pregnant women: a retrospective observational study. European Review for Medical and Pharmacological Sciences 21:4219–4227.
   PubMed Web of Science ®Google Scholar
• Paul C, Lagana 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. Gynecological Endocrinology 32:431–438.
   PubMed Web of Science ®Google Scholar
• Pintaudi B, Di Vieste G, Corrado F, Lucisano G, Giunta L, D'Anna R, et al. 2018. Effects of myo-inositol on glucose variability in women with gestational diabetes. European Review for Medical and Pharmacological Sciences. 22:6567–6572.
   PubMed Web of Science ®Google Scholar
• Pizzo A, Lagana AS, Barbaro L. 2014. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecological Endocrinology 30:205–208.
   PubMed Web of Science ®Google Scholar
• Porcaro G, Brillo E, Giardina I, Di Iorio R. 2015. Alpha Lipoic Acid (ALA) effects on subchorionic hematoma: preliminary clinical results. European Review for Medical and Pharmacological Sciences. 19:3426–3432.
   PubMed Web of Science ®Google Scholar
• Raffone E, Rizzo P, Benedetto V. 2010. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecological Endocrinology 26:275–280.
   PubMed Web of Science ®Google Scholar
• Ravanos K, Monastra G, Pavlidou T, Goudakou M, Prapas N. 2017. Can high levels of D-chiro-inositol in follicular fluid exert detrimental effects on blastocyst quality? European Review for Medical and Pharmacological Sciences 21:5491–5498.
   PubMed Web of Science ®Google Scholar
• Rotterdam EA-SPCWG. 2004. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81:19–25.
   Web of Science ®Google Scholar
• Rubino P, Palini S, Chigioni S, Carlomagno G, Quagliariello A, De Stefani S, et al. 2015. Improving fertilization rate in ICSI cycles by adding myoinositol to the semen preparation procedures: a prospective, bicentric, randomized trial on sibling oocytes. Journal of Assisted Reproduction and Genetics 32:387–394.
   PubMed Web of Science ®Google Scholar
• Sacchi S, Marinaro F, Tondelli D, Lui J, Xella S, Marsella T, et al. 2016. Modulation of gonadotrophin induced steroidogenic enzymes in granulosa cells by d-chiroinositol. Reproductive Biology and Endocrinology 14:52.
   PubMed Web of Science ®Google Scholar
• Sambuy Y, De Angelis I, Ranaldi G, Scarino ML, Stammati A, Zucco F. 2005. The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biology and Toxicology 21:1–26.
   PubMed Web of Science ®Google Scholar
• Santamaria A, Alibrandi A, Di Benedetto A, Pintaudi B, Corrado F, Facchinetti F, et al. 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 219:300 e301–300 e306.
   Web of Science ®Google Scholar
• Santamaria A, Di Benedetto A, Petrella E, Pintaudi B, Corrado F, D'Anna R, et al. 2016. Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial. The Journal of Maternal-Fetal & Neonatal Medicine 29:3234–3237.
   PubMed Web of Science ®Google Scholar
• Seli E, Duleba AJ. 2004. Treatment of PCOS with metformin and other insulin-sensitizing agents. Current Diabetes Reports 4:69–75.
   PubMedGoogle Scholar
• Stocco C. 2012. Tissue physiology and pathology of aromatase. Steroids 77:27–35.
   PubMed Web of Science ®Google Scholar
• Sullivan KM, Busa WB, Wilson KL. 1993. Calcium mobilization is required for nuclear vesicle fusion in vitro: implications for membrane traffic and IP3 receptor function. Cell 73:1411–1422.
   PubMed Web of Science ®Google Scholar
• Unfer V. 2010. Polycystic ovary syndrome: a vitamin deficiency? Floating a new pathogenesis hypothesis. European Review for Medical and Pharmacological Sciences 14:1101–1105.
   PubMed Web of Science ®Google Scholar
• Unfer V. 2018. Use of alpha-lactalbumin for the management of PCOS in inositols resistant women. European Review for Medical and Pharmacological Sciences 22:1873–1874.
   PubMed Web of Science ®Google Scholar
• Unfer V, Carlomagno G, Papaleo E, Vailati S, Candiani M, Baillargeon JP. 2014. Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reproductive Sciences 21:854–858.
   PubMed Web of Science ®Google Scholar
• Unfer V, Carlomagno G, Rizzo P, Raffone E, Roseff S. 2011a. Myo-inositol rather than D-chiro-inositol is able to improve oocyte quality in intracytoplasmic sperm injection cycles: a prospective, controlled, randomized trial. European Review for Medical and Pharmacological Sciences 15:452–457.
   PubMed Web of Science ®Google Scholar
• Unfer V, Facchinetti F, Orru B, Giordani B, Nestler J. 2017. Myo-inositol effects in women with PCOS: a meta-analysis of randomized controlled trials. Endocrine Connections 6:647–658.
   PubMed Web of Science ®Google Scholar
• 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. International Journal of Endocrinology 2016:1849162.
   PubMed Web of Science ®Google Scholar
• Unfer V, Porcaro G. 2014. Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome. Expert Review of Clinical Pharmacology 7:623–631.
   PubMed Web of Science ®Google Scholar
• Unfer V, Raffone E, Rizzo P, Buffo S. 2011b. 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. Gynecological Endocrinology 27:857–861.
   PubMed Web of Science ®Google Scholar
• Vitale SG, Rossetti P, Corrado F, Rapisarda AM, La Vignera S, Condorelli RA, et al. 2016. How to achieve high-quality oocytes? The key role of myo-inositol and melatonin. International Journal of Endocrinology. 2016:1–9.
   Web of Science ®Google Scholar
• Voglmayr JK, Amann RP. 1973. The distribution of free myo-inositol in fluids, spermatozoa, and tissues of the bull genital tract and observations on its uptake by the rabbit epididymis. Biology of Reproduction 8:504–513.
   PubMed Web of Science ®Google Scholar
• Walensky LD, Snyder SH. 1995. Inositol 1,4,5-trisphosphate receptors selectively localized to the acrosomes of mammalian sperm. The Journal of Cell Biology 130:857–869.
   PubMed Web of Science ®Google Scholar