Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation
Abstract
:1. Introduction
1.1. Background
1.2. Inositol in Insulin Signaling
1.3. Inositol in Gonadotropin Signaling
1.4. Inositol in Cellular Motility Phenomena
1.5. Opportunity for Inositol Supplementation
2. First Preclinical Evidence
2.1. Metabolic Maternal Outcomes
2.2. Fetal Outcomes
3. Clinical Applications
3.1. Myo-Inositol in the Pursuit of Pregnancy
3.2. Myo-Inositol in the Prevention of Gestational Diabetes Mellitus
3.3. Myo-Inositol in the Prevention of Neural Tube Defects
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | Patients | Protocol | Findings |
---|---|---|---|
Gerli et al. 2003 [22] | 283 PCOS women with oligomenorrhea or amenorrhea | Randomized, placebo-controlled, treatment with 100 mg twice a day for 14 weeks | Ovulation rate: 23% in the treatment group versus 13% in the control group |
Costantino et al. 2009 [23] | 42 PCOS women with oligomenorrhea, high serum free testosterone, and/or hirsutism | Double-blind, randomized, placebo-controlled, treatment with 2000 mg twice a day for 6 weeks | Ovulation rate: 69.5% in the treatment group versus 21% in the control group Progesterone peak value: 15.1 ng/mL in the treatment group versus 6.6 ng/mL in the control gorup |
Papaleo et al. 2007 [24] | 25 infertile women showing PCOS as the only apparent cause of infertility | Open-label treatment with 2000 mg twice a day for 6 months | Serum progesterone: 1.8 ± 0.7 ng/mL at baseline versus 10.5 ± 1.8 ng/mL after treatment Percentage of patients with at least one menstrual cycle: 0% at baseline versus 88% after treatment Percentage of patients with regular ovulations: 0% at baseline versus 72% after treatment Percentage of pregnancy achieved during the treatment: 40% |
Raffone et al. 2010 [25] | 120 anovulatory, infertile PCOS women | Randomized treatment for 6 months with 4000 mg/die myo-inositol versus 1500 mg/die metformin; nonpregnant patients from both groups underwent 37.5 U/die FSH treatment for a maximum of three times | Pregnancy rate after the first treatment: 26.1% in the metformin group versus 28.9% in the myo-inositol group Total pregnancy rate following FSH treatment: 36.6% in the metformin group versus 48.4% in the myo-inositol group |
Allah et al. 2020 [26] | 140 sub-fertile PCOS women | Open-label treatment with 2000 mg per day for 6 months | Percentage of patients with regular menstrual cycle: 0% at baseline versus 24.3% after three months versus 53.6% after six months Percentage of ovulating patients: 0% at baseline versus 38.6% after three months versus 72.1% after six months |
Study | Patients | Protocol | Findings |
---|---|---|---|
Lisi et al. 2012 [31] | 100 non-PCOS women with basal FSH <10 mUI/mL | Randomized, controlled treatment with 2000 mg twice a day for 3 months | Exogenous FSH required to reach follicular maturation: 2.084 UI in the treatment group versus 2.479 UI in the control group |
Caprio et al. 2015 [32] | 76 non-PCOS infertile women | Controlled treatment with 4000 mg/day for 3 months | Percentage of metaphase II oocytes: 80.5% in the treatment group versus 66.6% in the control group Ovarian sensitivity index: 1.88 ± 0.81 in the treatment group versus 1.54 ± 0.65 in the control group |
Study | Patients | Protocol | Findings |
---|---|---|---|
D’Anna et al. 2012 [43] | 98 pregnant PCOS women | Retrospective study of women taking 4000 mg/die myo-inositol throughout the whole pregnancy versus 1500 mg/die metformin until pregnancy occurs | GDM incidence: 17.4% in the treatment group versus 54% in the control group |
Matarrelli et al. 2013 [44] | 73 pregnant women, or intended to become pregnant, with glycemia ≥5.1 mmol/L or 92 mg/dL and ≤7.0 mmol/L or 126 mg/dL | Randomized, double-blind, placebo-controlled treatment with 4000 mg/die for the entire pregnancy | GDM incidence: 6% in the treatment group versus 71% in the control group Need for insulin: 3% in the treatment group versus 21% in the control group Neonatal hypoglycemia: 0% in the treatment group versus 26% in the control group |
D’Anna et al. 2013 [45] | 197 pregnant women with a parent with type 2 diabetes | Randomized, placebo-controlled treatment with 2000 mg twice per day | GDM incidence: 6% in the treatment group versus 15.3% in the control group Macrosomia cases: 0 in the treatment group versus 7 in the control group Birthweight: 3111 ± 447 g in the treatment group versus 3273 ± 504 g in the control group |
D’Anna et al. 2015 [46] | 201 pregnant women with BMI ≥ 30 kg/m2 | Randomized, placebo-controlled treatment with 2000 mg twice per day | GDM incidence: 14% in the treatment group versus 33.6% in the control group |
Santamaria et al. 2016 [47] | 207 women with BMI > 25 and <30 kg/m2 and fasting plasma glucose ≤126 mg/dL and/or glycemia <200 mg/dL | Randomized, placebo-controlled treatment with 2000 mg twice per day from the first trimester to the end of the pregnancy | GDM incidence: 11.6% in the treatment group versus 27.4% in the control group |
Vitale et al. 2020 [49] | 223 women with BMI > 25 and <30 kg/m2 and fasting plasma glucose ≤126 mg/dL and/or glycemia <200 mg/dL | Randomized, placebo-controlled treatment with 2000 mg twice per day from the first trimester to three weeks after delivery | GDM incidence: 8.2% in the treatment group versus 21.2% in the control group Weight gain: 8.33 ± 2.47 kg in the treatment group versus 9.31 ± 2.66 kg in the control group Total body water in the third trimester: 51.30 ± 4.65 L in the treatment group versus 53.82 ± 4.13 L in the control group |
Celentano et al. 2018 [50] | 157 nonobese pregnant women with fasting glycemia ≥5.1 mmol/L or 92 mg/dL and <7.0 mmol/L or 126 mg/dL | Randomized, placebo-controlled treatment for the entire pregnancy with 2000 mg myo-inositol twice per day, 500 mg d-chiro-inositol per day, or 13.8 mg d-chiro-inositol and 550 mg myo-inositol twice per day | GDM incidence: 5.1% in the myo-inositol group versus 34.4% in the d-chiro-inositol group versus 38.2% in the combined group versus 61.5% in the control group Neonatal hypoglycemia: 0% in the myo-inositol group versus 15.6% in the d-chiro-inositol group versus 8.8% in the combined treatment group versus 21.1% in the control group |
Study | Patients | Protocol | Findings |
---|---|---|---|
Cavalli et al. 2008 [63] | 3 women with at least one previous pregnancy affected by folate-resistant NTD | Open-label treatment with 500 mg per day from at least two months before and until 60 days after conception | NTD incidence: 0% |
Cavalli et al. 2011 [64] | 9 women with at least one previous pregnancy affected by folate-resistant NTD | Open-label treatment with 1000 mg per day from at least two months before and until 60 days after conception | NTD incidence: 0% |
Greene et al. 2016 [65] | 47 randomized and 22 non-randomized women with at least one previous pregnancy affected by NTD | Randomized, double-blind, placebo-controlled treatment with 500 mg twice per day; women who declined randomization decided to take myo-inositol plus folic acid (19 patients), or folic acid only (3 patients) | NTD incidence in randomized patients: 0% in the treatment group versus 5.3% in the control group NTD cases in the non-randomized patients: 0 in the myo-inositol plus folic acid group versus 2 in the folic acid alone group Overall NTD incidence: 0% in the treatment group versus 13.63% in the control group |
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Gambioli, R.; Forte, G.; Buzzaccarini, G.; Unfer, V.; Laganà, A.S. Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation. Pharmaceuticals 2021, 14, 504. https://doi.org/10.3390/ph14060504
Gambioli R, Forte G, Buzzaccarini G, Unfer V, Laganà AS. Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation. Pharmaceuticals. 2021; 14(6):504. https://doi.org/10.3390/ph14060504
Chicago/Turabian StyleGambioli, Riccardo, Gianpiero Forte, Giovanni Buzzaccarini, Vittorio Unfer, and Antonio Simone Laganà. 2021. "Myo-Inositol as a Key Supporter of Fertility and Physiological Gestation" Pharmaceuticals 14, no. 6: 504. https://doi.org/10.3390/ph14060504