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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
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.
A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes.
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.
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.
... It is difficult to rationalize as to why there was a divergence in opinion between the two groups. One explanation may be found in the 2023 edition of the international PCOS guidelines, which highlighted myo-inositol as having potential in PCOS, but still classified the supplement as an experimental treatment falling short of formally recommending myoinositol therapy, due to a limitation of available information and the urgent need for more evidence-based data [31]. Another potential explanation for this difference in opinion, is that Italian gynecologists have less experience prescribing metformin in comparison to endocrinologists, who are much more familiar with the drug. ...
To gather the current opinion among Italian gynecologists and endocrinologists regarding the definition, diagnosis, and treatment of polycystic ovary syndrome (PCOS).
A Delphi survey consisting of 26 statements was designed by a nine-member panel (consisting of members from the Italian Society of Endocrinology (SIE) and the Experts Group AQon Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS)) and distributed to 102 experts in PCOS across the fields of gynecology and endocrinology. Consensus was defined as an agreement between at least 70% of responders. Participants completed three rounds of statements, ranking their level of agreement.
Of the initial 26 statements, 25 reached an adequate consensus, with an overall response rate of 73%. The statements were divided into three sections: definition and current understanding, diagnosis, and treatment. Of the statements that reached consensus, near total agreement was reached in the first two sections, whereas there was a divergence of opinion in terms of optimum treatment strategy between the gynecology and endocrinology subgroups.
It was agreed that the current clinical guidelines are inadequate for clinical and scientific practice, with most responders advocating for the inclusion of metabolic factors. Furthermore, the consensus opinion advocated for the diversification of hyperandrogenic vs. non-hyperandrogenic phenotypes. This survey gives a snapshot of the current understanding of PCOS in the Italian healthcare community.
Optimal nutrition requires complete provision of the human needs not only for energy, macro- and micronutrients, but also for minor biologically active substances. Some of the most promising chemoprotectors are glucosinolates and their active derivatives, such as 3,3’-diindolylmethane (DIM). DIM has the ability to inhibit the development and progression of neoplasia by regulating multiple intracellular signaling pathways. Currently, the clinical efficacy of DIM is being studied in breast and prostate cancer, and the possibility of using DIM’s antioxidant and anti-inflammatory properties in neurodegenerative, metabolic and immune diseases is being investigated.
Study question:
What is the recommended assessment and management of those with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertise, and consumer preference?
Summary answer:
International evidence-based guidelines address prioritized questions and outcomes and include 254 recommendations and practice points, to promote consistent, evidence-based care and improve the experience and health outcomes in PCOS.
What is known already:
The 2018 International PCOS Guideline was independently evaluated as high quality and integrated multidisciplinary and consumer perspectives from 6 continents; it is now used in 196 countries and is widely cited. It was based on best available, but generally very low- to low-quality, evidence. It applied robust methodological processes and addressed shared priorities. The guideline transitioned from consensus-based to evidence-based diagnostic criteria and enhanced accuracy of diagnosis, whilst promoting consistency of care. However, diagnosis is still delayed, the needs of those with PCOS are not being adequately met, the evidence quality was low, and evidence-practice gaps persist.
Study design, size, and duration:
The 2023 International Evidence-based Guideline update re-engaged the 2018 network across professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. Extensive evidence synthesis was completed. Appraisal of Guidelines for Research and Evaluation II (AGREEII)-compliant processes were followed. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, feasibility, acceptability, cost, implementation, and ultimately recommendation strength, and diversity and inclusion were considered throughout.
Participants/materials, setting, and methods:
This summary should be read in conjunction with the full guideline for detailed participants and methods. Governance included a 6-continent international advisory and management committee, 5 guideline development groups, and paediatric, consumer, and translation committees. Extensive consumer engagement and guideline experts informed the update scope and priorities. Engaged international society-nominated panels included paediatrics, endocrinology, gynaecology, primary care, reproductive endocrinology, obstetrics, psychiatry, psychology, dietetics, exercise physiology, obesity care, public health, and other experts, alongside consumers, project management, evidence synthesis, statisticians, and translation experts. Thirty-nine professional and consumer organizations covering 71 countries engaged in the process. Twenty meetings and 5 face-to-face forums over 12 months addressed 58 prioritized clinical questions involving 52 systematic and 3 narrative reviews. Evidence-based recommendations were developed and approved via consensus across 5 guideline panels, modified based on international feedback and peer review, independently reviewed for methodological rigour, and approved by the Australian Government National Health and Medical Research Council.
Main results and the role of chance:
The evidence in the assessment and management of PCOS has generally improved in the past 5 years but remains of low to moderate quality. The technical evidence report and analyses (∼6000 pages) underpin 77 evidence-based and 54 consensus recommendations, with 123 practice points. Key updates include the following: (1) further refinement of individual diagnostic criteria, a simplified diagnostic algorithm, and inclusion of anti-Müllerian hormone levels as an alternative to ultrasound in adults only; (2) strengthening recognition of broader features of PCOS including metabolic risk factors, cardiovascular disease, sleep apnoea, very high prevalence of psychological features, and high risk status for adverse outcomes during pregnancy; (3) emphasizing the poorly recognized, diverse burden of disease and the need for greater healthcare professional education, evidence-based patient information, improved models of care, and shared decision-making to improve patient experience, alongside greater research; (4) maintained emphasis on healthy lifestyle, emotional well-being, and quality of life, with awareness and consideration of weight stigma; and (5) emphasizing evidence-based medical therapy and cheaper and safer fertility management.
Limitations and reasons for caution:
Overall, recommendations are strengthened and evidence is improved but remains generally low to moderate quality. Significantly greater research is now needed in this neglected, yet common condition. Regional health system variation was considered and acknowledged, with a further process for guideline and translation resource adaptation provided.
Wider implications of the findings:
The 2023 International Guideline for the Assessment and Management of PCOS provides clinicians and patients with clear advice on best practice, based on the best available evidence, expert multidisciplinary input, and consumer preferences. Research recommendations have been generated, and a comprehensive multifaceted dissemination and translation programme supports the guideline with an integrated evaluation programme.
Objective:
Insulin resistance and hyperinsulinemia plays an important role in pathogenesis of polycystic ovary syndrome (PCOS). Metformin, Myoinositol and d-chiro-inositol acts as insulin sensitizers and exerts a beneficial effects in PCOS. The objective is to compare the effect of metformin monotherapy versus a combination of metformin with Myoinositol and d-chiro-inositol in PCOS.
Design:
This study is a randomized controlled trial conducted over a period of 6 months. All overweight and obese women with PCOS with the age group between 18 and 35 were included and randomized into two groups, 27 in the metformin monotherapy arm and 26 in the myoinositol combination arm.
Patients and measurements:
The variables assessed were duration of menstrual cycle, anthropometric parameters, modified Ferriman Gallwey score, global acne score, Fasting insulin, HOMA-IR, fasting lipid profile, serum testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, anti-Mullerian hormone, and pelvic ultrasound to assess ovarian volume, PCOS Questionnaire score. Changes in the parameters from baseline at the end of 6 months of treatment were assessed and compared between the groups.
Results:
Menstrual cycle regularity improved in both groups with significantly greater improvement in the group receiving myoinositol-based therapy (p < .001). Pregnancy rate was equal in both the arms. There was a significant improvement in PCOSQ score in myoinositol-based therapy group (p < .001). However, there was no statistically significant difference in other hormonal, metabolic parameters between two groups in spite of symptomatic benefits.
Conclusions:
The addition of myoinositol to metformin exerts additional benefits in improving menstrual cycle regularity, and quality of life in women with PCOS.
Myo-inositol is a natural polyol, the most abundant among the nine possible structural isomers available in living organisms. Inositol confers some distinctive traits that allow for a striking distinction between prokaryotes and eukaryotes, the basic clusters into which organisms are partitioned. Inositol cooperates in numerous biological functions where the polyol participates or by furnishing the fundamental backbone of several related derived metabolites, mostly obtained through the sequential addition of phosphate groups (inositol phosphates, phosphoinositides, and pyrophosphates). Overall myo-inositol and its phosphate metabolites display an entangled network, which is involved in the core of the biochemical processes governing critical transitions inside cells. Noticeably, experimental data have shown that myo-inositol and its most relevant epimer D-chiro-inositol are both necessary to permit a faithful transduction of insulin and of other molecular factors. This improves the complete breakdown of glucose through the citric acid cycle, especially in glucose-greedy tissues, such as the ovary. In particular, while D-chiro-inositol promotes androgen synthesis in the theca layer and down-regulates aromatase and estrogen expression in granulosa cells, myo-inositol strengthens aromatase and FSH receptor expression. Inositol effects on glucose metabolism and steroid hormone synthesis represent an intriguing area of investigation, as recent results have demonstrated that inositol-related metabolites dramatically modulate the expression of several genes. Conversely, treatments including myo-inositol and its isomers have proven to be effective in the management and symptomatic relief of a number of diseases associated with the endocrine function of the ovary, namely polycystic ovarian syndrome.
Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women, in which, besides chronic anovulation/oligomenorrhea and ovarian cysts, hyperandrogenism plays a critical role in a large fraction of subjects. Inositol isomers—myo-Inositol and D-Chiro-Inositol—have recently been pharmacologically effective in managing many PCOS symptoms while rescuing ovarian fertility. However, some disappointing clinical results prompted the reconsideration of their specific biological functions. Surprisingly, D-Chiro-Ins stimulates androgen synthesis and decreases the ovarian estrogen pathway; on the contrary, myo-Ins activates FSH response and aromatase activity, finally mitigating ovarian hyperandrogenism. However, when the two isomers are given in association—according to the physiological ratio of 40:1—patients could benefit from myo-Ins enhanced FSH and estrogen responsiveness, while taking advantage of the insulin-sensitizing effects displayed mostly by D-Chiro-Ins. We need not postulate insulin resistance to explain PCOS pathogenesis, given that insulin hypersensitivity is likely a shared feature of PCOS ovaries. Indeed, even in the presence of physiological insulin stimulation, the PCOS ovary synthesizes D-Chiro-Ins four times more than that measured in control theca cells. The increased D-Chiro-Ins within the ovary is detrimental in preserving steroidogenic control, and this failure can easily explain why treatment strategies based upon high D-Chiro-Ins have been recognized as poorly effective. Within this perspective, two factors emerge as major determinants in PCOS: hyperandrogenism and reduced aromatase expression. Therefore, PCOS could no longer be considered a disease only due to increased androgen synthesis without considering the contemporary downregulation of aromatase and FSH receptors. Furthermore, these findings suggest that inositols can be specifically effective only for those PCOS phenotypes featured by hyperandrogenism.
Background: The medical management of PCOS is fast changing from the combination hormonal pills/progesterone for cycle regularisation, cosmetological treatment of acne and hirsutism to management of obesity and insulin resistance. This study evaluates the effects of the insulin sensitisers in improving the clinical and hormonal alterations in cases of PCOS and improving the reproductive outcomes.Methods: This 3-arm prospective randomized comparative study was done from August 2015 to July 2016 in the Department of Obstetrics and Gynaecology at SCB MCH, Cuttack wherein patients of PCOS were studied based on treatment with metformin, myoinositol or both.Results: Myoinositol helped in the resumption of spontaneous menstrual cycles in 66.66% of women with PCOS with menstrual complaints, whereas the same effect in patients who took metformin was only in 15.78%, which was not significant. Use of myoinositol in Infertile women with PCOS resulted in a pregnancy in 57.14% of women, without the need of any ovulation inducing agent while use of metformin gave a pregnancy in all the 9 patients, thought 5 out of them required clomiphene citrate for ovulation induction. With myoinositol there was a reduction in weight, BMI, LH/FSH ratio, acne and hirsutism. Metformin has resulted in a decrement of body weight, BMI and acne only.Conclusions: This study conclusively proves that myoinositol has a definitive role in decreasing the ovarian dysfunction of PCOS. There has been a significant improvement in the symptom profile, weight loss and a significant change in the hormonal parameters.
Background
Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects.
Objective
Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS.
Methods
The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs).
Results
Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85).
Conclusion
Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin.
Trial registration
PROSPERO registration number: CRD42021283275.
Background:
This study strove to investigate the hypothesis that a low dosage of myo-inositol supplementation might decrease the likelihood of gestational diabetes in overweight, pregnant women.
Methods:
A randomized, double-blind, controlled trial was performed on 60 eligible overweight, pregnant women at 12-14 weeks of gestation at two Iranian obstetric clinics. The participants were divided into two groups based on blocked randomization. The myo-inositol group received 2000 mg plus 400 μg folic acid daily and the control group received 400 μg of folic acid daily from 14 - 24 gestational weeks. The occurrence of gestational diabetes was determined based on 75-g 2-hour oral glucose tolerance test (OGTT) at 24-28 gestational weeks, which was the primary outcome of the study. The secondary outcomes were: the evaluation of insulin therapy, insulin resistance and lipid profile, gestational weight gain, and fetal and maternal outcomes.
Results:
The incidence of gestational diabetes in myo-inositol group was noticeably minimized compared with that in the control group (RR 0.29, 95% CI 0.09-0.94, p=0.037). There were no differences between the two groups in terms of fasting blood sugar, fasting insulin, HOMA-IR, insulin therapy, and triglyceride. There was no report of severe adverse drug reactions, either.
Conclusions:
The absolute risk reduction and the ''Number-Needed-to-Treat'' for gestational diabetes were 26.8% (95% CI, 5.6-48) and 3.7 (95% CI, 2.1-18.0), respectively. Hence, it can be concluded that approximately one out of every four overweight pregnant women receiving myo-inositol benefitted from its daily intake.
Objectives
To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women.
Design
A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation.
Setting
Five inner city UK National Health Service hospitals
Participants
Multiethnic pregnant women at 12⁺⁰ and 15⁺⁶ weeks’ gestation with risk factors for gestational diabetes.
Interventions
2 g of myo-inositol or placebo, both included 200 µg folic acid, twice daily until delivery.
Primary outcome measures
Rates of recruitment, randomisation, adherence and follow-up.
Secondary outcome measures
Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs.
Results
Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks’ and 34% (SD 41) at 36 weeks’ gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference −0.6, 95% CI −1.2 to 0.0 and −2.69, 95% CI −5.26 to −0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence.
Conclusions
A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol.
Trial registration number
ISRCTN48872100.
Background:
Atrial fibrillation (AF) is a common concern in patients with heart disease, especially those with acute decompensated heart failure (ADHF). We conducted a cross-sectional study to determine the frequency of AF and associated risk factors among patients with ADHF at a tertiary care hospital in Peshawar, Pakistan.
Methods:
We conducted a cross-sectional analytical study of hospitalized patients with ADHF treated in a tertiary care hospital in Peshawar, Pakistan, from June 5 to October 30, 2021. The study's primary outcome was the proportion of patients with ADHF who had AF, and our secondary outcome was examining the risk factors for AF. The College of Physicians and Surgeons Pakistan provided ethical approval of the study design. Data were analyzed using IBM SPSS Statistics for Windows version 24.0 (IBM Corp., Armonk, NY, USA). We applied the chi-square test to compare the proportion of AF concerning risk factors (i.e., comorbidities).
Results:
One hundred ninety-four patients with ADHF were included in the study; 54.6% were male and 45.4% female. Most (56.7%) were older than 60, and 38.1% were aged 40-60. The prevalence of AF was 38.1%. Diabetes, hypertension, previous stroke, myocardial infarction (MI), and chronic obstructive pulmonary disease (COPD) were the most common comorbidities. All patients with ADHF with AF also had MI and hypertension. Patients of known coronary artery disease (CAD) but without MI, previous percutaneous coronary intervention (PCI), or coronary artery bypass graft (CABG) surgery were less associated with AF than other comorbidities.
Conclusions:
We conducted this study to determine the incidence of AF among patients with ADHF. AF occurs in a significant amount of patients with ADHF, and the risk factors associated with AF in these patients include hypertension, history of MI, diabetes, and COPD. Healthcare professionals should screen patients with ADHF for AF, especially those with common risk factors.
Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.
Myo-inositol (Myo) improves insulin resistance, glucose metabolism, and helps gestational diabetes (GDM) management. GDM is associated with a pro-inflammatory state and increased oxidative stress, which are both involved in vascular damage in diabetes. Our aim was to study Myo anti-inflammatory/antioxidant potential effects on an in vitro model of human umbilical vein endothelial cells (HUVECs). To this end, monocyte cell adhesion to HUVECs, adhesion molecule membrane exposure, and oxidative stress levels were determined in cells from control (C-) and GDM women treated during pregnancy either with diet only (GD-) or with diet plus Myo (GD+Myo). To deeply study the vascular effects of Myo, the same evaluations were performed in C- and GD-HUVECs following 48 h in vitro stimulation with Myo. Notably, we first observed that GD-HUVECs obtained from women assuming Myo supplementation exhibited a significantly decreased number of monocytes that adhered to endothelial cells, less adhesion molecule exposure, and lower intracellular reactive oxygen species (ROS) levels in the basal state as compared to GD-HUVECs obtained from women treated by diet only. This Myo anti-inflammatory/antioxidant effect was confirmed by 48 h in vitro stimulation of GD-HUVECs as compared to controls. Altogether, these results strongly suggest that Myo may exert protective actions against chronic inflammation induced by endothelial dysfunction in diabetes.
Objective
To compare the effects of metformin alone versus combined therapy of metformin with myoinositol (MI) plus D-chiro-inositol (DCI) in women with polycystic ovary syndrome (PCOS).
Materials and methods
This is a prospective, non-blinded randomized controlled trial conducted in newly diagnosed PCOS women aged 18 to 45 years. Group I received metformin 500 mg twice a day orally for 6 months while group II received metformin 500 mg twice a day orally along with MI 550 mg plus DCI 150 mg twice daily orally for six months. The primary outcome was a change in clinical, metabolic and hormonal parameters of the two groups from baseline to the end of six months of treatment.
Results
A total of 72 patients were randomized into two groups of 36 patients each. Statistically, a significant difference was seen in terms of mean global acne score (p=0.004) and cycle regularity (p=0.034) after six months of treatment in group II. A significant difference in values of luteinizing hormone (LH) (p=0.002), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio (p=0.007), mean cholesterol (p=0.040), mean high-density lipoprotein (HDL) (p=0.049), mean low-density lipoprotein (LDL) (p=0.0001) and postprandial insulin (p=0.005) was also seen in group II at the end of treatment duration. No significant difference was seen between the two groups in terms of mean FSH, mean testosterone, mean dehydroepiandrosterone sulfate (DHEAS), mean triglyceride, mean fasting and postprandial blood sugar, fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) index.
Conclusion
Combined therapy with metformin and MI plus DCI in women with PCOS and insulin resistance seems promising with the need for further studies with a greater sample size to evaluate the efficacy of this treatment.
Pregnancy is a complex process, featuring several necessary changes in women’s physiology. Most women undergo healthy pregnancies; even so, several women experience reduced fertility or pathologies related to the pregnancy. In the last years, researchers investigated several molecules as promoters of fertility. Among all, myo-inositol (myo-ins) represents a safe compound that proved useful in issues related to fertility and pregnancy. In fact, myo-ins participates in several signaling processes, including the pathways of insulin and gonadotropins, and, therefore, it is likely to positively affect fertility. In particular, several clinical trials demonstrate that its administration can have therapeutic effects in infertile women, and that it can also be useful as a preventive treatment during pregnancy. Particularly, myo-ins could prevent the onset of neural tube defects and the occurrence of gestational diabetes mellitus, promoting a trouble-free gestation. Due to the safety and efficiency of myo-ins, such a treatment may also substitute several pharmaceuticals, which are contraindicated in pregnancy.
To verify whether myo-inositol plus α-lactalbumin may reduce insulin resistance and excessive fetal growth in women with gestational diabetes mellitus. In a 12-month period, 120 women with a diagnosis of gestational diabetes mellitus were consecutively enrolled with an allocation of 1:1 in each group and randomly treated with myo-inositol plus α-lactalbumin plus folic acid (treated group) or folic acid (control group) for 2 months. Primary outcome was the variation of insulin resistance through the study evaluated by HOMA-IR. Secondary outcome was the evaluation, through the study, of fetal growth by ultrasound measurements of abdominal circumference centiles and estimated fat thickness. Some clinical outcomes were also considered. After 2 months, in the treated group, a significant reduction in insulin resistance (HOMA values 3.1 ± 1.4 vs 6.1 ± 3.4, p = 0.0002) and fetal growth was shown (Abdominal circumference centiles 54.9 ± 23.5 vs 67.5 ± 22.6, P = 0.006). Among clinical outcomes, a significant decrease in the rate of women who needed insulin (6.7% vs 20.3%, p = 0.03) and of pre-term birth (0 vs 15.2%, p = 0.007) was evidenced. A combination of myo-inositol and α-lactalbumin may reduce insulin resistance and excessive fetal growth.
Clinical trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT 03763669, first posted date 04/12/2018; last posted date December 06/12/2018.
Objective:
Inositol is a carbocyclic sugar polyalcohol. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of major physiological and clinical relevance: myo-inositol and D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in kidney, brain and liver and are necessary for functions, such as signal transduction, metabolic flux, insulin signaling, regulation of ion-channel permeability, stress response and embryo development. In this narrative review, we summarize the mechanisms by which myo-inositol and D-chiro-inositol can be synthesized and absorbed and their possible role in the etiopathogenesis of neural tube defects.
Materials and methods:
We performed an online search in the PubMed database using the following keywords: "inositol", "D-chiro-inositol", "myo-inositol", "neural tube defects and inositol".
Results:
Inositol requirements are partly met by dietary intake, while the rest is synthesized endogenously. Inositol deficiency may be involved in the pathogenesis of diseases, such as metabolic syndrome, spina bifida (a neural tube defect), polycystic ovary syndrome and diabetes. Supplementation of the two inositol stereoisomers, D-chiro-inositol and myo-inositol is important to prevent these conditions.
Conclusions:
Inositol is fundamental for signal transduction in the brain, kidneys, reproductive organs and other tissues in response to neurotransmitters, hormones and growth factors. Various genes are involved in inositol metabolism and associated pathways. Altered inositol concentrations are observed in several diseases. Analysis of the genes involved in inositol metabolism may provide important information for the clinical management of these conditions.
We report here the in vivo conversion of [3H]myoinositol to [3H]chiroinositol. After labeling intraperitoneally with [3H]myoinositol for 3 days to reach radioisotope equilibrium in urine, [3H]chiroinositol was isolated from tissues and purified after 6 N HCl hydrolysis by two sequential paper chromatographies and high performance liquid chromatography (HPLC). Percent conversion of [3H]myoinositol to [3H]chiroinositol was highest in urine (36%), liver (8.8%), muscle (8.8%), and blood (7.6%) with intestine, brain, kidney, spleen, and heart decreasing in percentage from 2.8 to 0.7%. Labeling of other inositol isomers including scyllo-, neo-, and epi-, and mucoinositol was minimal, approximately 0.06% of [3H]myoinositol. Glucose was unlabeled, but glucuronate, the product of myoinositol oxidation, was labeled up to 1.5% of the [3H] myoinositol. Acid hydrolysates of combined inositol-containing phospholipids contain significant labeled chiroinositol. [3H]Phosphatidylinositols and [3H]glycosylphosphatidylinositols were extracted from liver, muscle, and blood, isolated by thin layer chromatography, and inositols purified by HPLC after acid hydrolysis. Percent conversion of [3H]myoinositol to [3H] chiroinositol was highest in blood (60.4%) followed by muscle (7.7%) and liver (2.2%).
Objective: To assess the efficacy of myoinositol in the management of patients with Polycystic ovarian syndrome (PCOS) Methods: It was quasi experimental study conducted inDepartment of Obstetrics and Gynecology Services institute of Medical Sciences, Services Hospital, Lahore from 30-6-2018 to 31-12-2018. 140 sub fertile patients with PCOS were selected through random sampling. Patients were given 2gram of myoinositol/day. The effect was assessed after 3 and 6 months of treatment by monthly menstrual cycle regularity and ovulation. All this information was recorded in proforma. Results: The mean age of patients was 26.90±5.52years. The mean BMI of patients was 37.38±4.08kg/m2. After 3 months of treatment, menstrual cycle become regular in 34 (24.3%) patients and ovulation occurred in 54 (38.6%) cases. After 6 months of treatment, menstrual cycle become regular in 75 (53.6%) patients and ovulation occurred in 101 (72.1%) cases. Conclusion: The myoinositol is an effective treatment in terms of regularity of menstrual cycle and ovulation induction in subfertile women with PCOS. Keywords: Myoinositol, Polycystic ovarian syndrome, Menstrual irregularity, Ovulation
Background:
An ENDO-European Reference Network (ERN) initiative was launched that was endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology with 22 participants from the ENDO-ERN and the two societies. The aim was to update the practice guidelines for the diagnosis and management of congenital hypothyroidism (CH). A systematic literature search was conducted to identify key articles on neonatal screening, diagnosis, and management of primary and central CH. The evidence-based guidelines were graded with the Grading of Recommendations, Assessment, Development and Evaluation system, describing both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion.
Summary:
The recommendations include the various neonatal screening approaches for CH as well as the etiology (also genetics), diagnostics, treatment, and prognosis of both primary and central CH. When CH is diagnosed, the expert panel recommends the immediate start of correctly dosed levothyroxine treatment and frequent follow-up including laboratory testing to keep thyroid hormone levels in their target ranges, timely assessment of the need to continue treatment, attention for neurodevelopment and neurosensory functions, and, if necessary, consulting other health professionals, and education of the child and family about CH. Harmonization of diagnostics, treatment, and follow-up will optimize patient outcomes. Lastly, all individuals with CH are entitled to a well-planned transition of care from pediatrics to adult medicine.
Conclusions:
This consensus guidelines update should be used to further optimize detection, diagnosis, treatment, and follow-up of children with all forms of CH in the light of the most recent evidence. It should be helpful in convincing health authorities of the benefits of neonatal screening for CH. Further epidemiological and experimental studies are needed to understand the increased incidence of this condition.
This study aims to evaluate the effects of myo-inositol supplementation on gestational diabetes mellitus (GDM) rates and body water distribution in overweight non-obese women. 223 overweight non-obese women pregnant were randomly assigned to the treatment group (2 g of myo-inositol plus 200 µg of folic acid) or to the placebo one (200 µg of folic acid). The treatment lasted until three weeks after delivery. A tetrapolar impedance analyser was used to study body composition. The incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group. There was a significant increase in TBW, ECW and ICW values in the placebo group compared to the myo-inositol group. We have recorded a significant reduction in the overall incidence of pregnancy-induced hypertension in the myo-inositol group compared with the placebo group. Our results demonstrate the effectiveness of myo-inositol supplementation in preventing GDM in overweight non-obese pregnant women.
Introduction:
Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs).
Areas covered:
In view of the recent knowledge, changes of nutritional and physical activity habits ameliorate glycemic control during pregnancy and in turn improve maternal and neonatal health outcomes. Recently, a series of small clinical and experimental studies indicated that supplementation with inositols, a family of insulin sensitizers, was associated with beneficial impact for both GDM and NTDs.
Expert opinion:
Herein, we discuss the most significant scientific evidence supporting myo-inositol administration as a prophylaxis for the above-mentioned conditions.
Introduction:
High levels of anti-Mullerian hormone and a high antral follicle count in women with polycystic ovary syndrome, reflecting increased ovarian antral follicles, predisposes them to have a high number of retrieved oocytes with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and an increased risk of ovarian hyperstimulation syndrome. Inositols, which act as insulin sensitizers, have the potential to alter folliculogenesis and the functional ovarian reserve, with subsequent benefits to reproductive outcomes following IVF/ICSI treatment. Published literature is, however, unable to provide definitive evidence of its efficacy. The objective of our review was to evaluate the effect of inositols on anti-Mullerian hormone, antral follicle count and reproductive outcomes in women with polycystic ovary syndrome undergoing IVF/ICSI.
Material and methods:
We performed a literature search using standard methodology recommended by Cochrane. Randomized controlled trials and non-randomized studies comparing inositols with no treatment, placebo or other treatment were included in the review. Using standard methodology recommended by Cochrane we pooled results using the random effects model; our findings were reported as relative risk or mean differences. PROSPERO registration: CRD42017082275.
Results:
We included 18 trials. The primary outcome was a change in anti-Mullerian hormone and antral follicle count before and after treatment, for which data were unsuitable for meta-analysis. A narrative review showed no consistent direction or size of effect. A meta-analysis for the secondary outcomes showed no evidence of a significant difference between inositol and control groups for any outcome: number of oocytes (mean difference -0.39, 95% confidence interval [CI] -1.11 to 0.33), number of metaphase II oocytes (mean difference 0.29, 95% CI -0.83 to 1.40), number of top grade embryos (risk ratio [RR] 1.02, 95% CI 0.93-1.12), clinical pregnancy rate (RR 1.16, 95% CI 0.87-1.53), and risk of ovarian hyperstimulation syndrome (RR 0.73, 95% CI 0.39-1.37). The quality of evidence was assessed as very low.
Conclusions:
There is insufficient evidence for an effect of inositols on ovarian reserve markers and to support their use as pretreatment before IVF/ICSI in women with polycystic ovary syndrome.
Purpose
The purpose is a comparison of effectiveness of myo-inositol and metformin in infertile women with polycystic ovary syndrome (PCOS) treated with letrozole.
Methods
This study is a randomized single-blind controlled clinical trial undertaken in 150 infertile PCOS women. For all patients, letrozole is prescribed at a dose of 7.5 mg per day from the third day of menstruation for 5 days. Patients who did not ovulate were included and divided into three pretreatment groups: group I(control group), 200 µg of folic acid (as a placebo); group II, 1500 mg of metformin daily plus 200 µg of folic acid, and group III, inositol 2 g plus 200 µg of folic acid received twice daily for 3 months. In the last cycle, 7.5 mg letrozole was prescribed for the induction of ovulation. Primary outcomes were ovary function and pregnancy.
Results
The ovarian function was not significantly different in those groups, whereas the ovarian function of inositol + folic acid group in normal BMI found significantly higher than other BMI spectra. In addition, the ovarian function is significantly higher in the inositol + folic acid group by increasing the infertility duration. The incidence of pregnancy is lower in letrozole + folic acid + inositol group than the other groups; however, it is not significant.
Conclusion
The addition of inositol and metformin to the treatment of infertile PCOS women with letrozole resistance improves the ovarian function; however, it is not significant. Of note, inositol was more effective than metformin in patients with normal BMI.
IRCT registration number
IRCT2017070234845N1
Context
Increased circulating insulin levels contribute to hyperandrogenism in polycystic ovarian syndrome (PCOS) which causes a derangement in folliculogenesis, thus contributing to polycystic morphogenesis of the ovaries and a higher than normal anti-Mullerian hormone (AMH). A high AMH is an indicator of either stubborn anovulation or a predictor of ovarian hyperstimulation syndrome. Hence, it is postulated that the use of insulin sensitizers will reduce insulin resistance, hyperandrogenism, and subsequently serum AMH levels and will convert anovulatory cycles to ovulatory.
Aim
To study the effect of insulin sensitizers on raised serum AMH levels in infertile women with PCOS.
Settings and Design
This was a prospective interventional randomized single tertiary center study.
Methodology
The study was conducted from August 2015 to April 2016. Infertile patients with PCOS as defined by the Rotterdam criteria with raised AMH (>5 ng/ml) levels were enrolled in the study under strict inclusion and exclusion criteria. The sample size was 105 patients. Cycle regularity, day 2–antral follicle count (AFC), luteinizing hormone, AMH levels, modified Ferriman–Gallwey score (mFGS), and acne score were recorded before starting the intervention. Patients were randomized into three equal groups of 35 each. Group A received metformin alone, Group B metformin plus myoinositol, and Group C only myoinositol. After completion of 3 months of pretreatment, the same parameters were rechecked.
Statistical Analysis Used
Univariate analysis and Chi-square test were used for statistical analysis.
Results
Of 105 patients, 95 completed treatment and the rest 10 dropped out. There was a reduction in AMH in all groups of insulin sensitizers with significant fall in the metformin only group. Cycle regularity, reduction in AFC, mFGS, and grade of acne were also obtained.
Conclusions
Therapy with insulin sensitizers in PCOS women with raised AMH reduces the AMH levels, converts irregular menstrual cycles to regular, and reduces clinical hyperandrogenism.
Mice exposed to continuous light undergo functional and histological changes that mimic those of human Polycystic Ovary Syndrome (PCOS). We herein induced the syndrome by exposing 30‐day‐old females to 10 weeks of permanent light. Ovarian morphology and histology, as well as reproductive parameters (time of observed pregnancy/delivery) were investigated. Ovaries of PCOS‐modeled mice showed lack of tertiary follicles and corpora lutea, altered ovarian architecture, and increased thickness of the theca layer. When mice were returned to a normal light‐dark regimen for 10 days, a slight, spontaneous improvement occurred, whereas a quick and almost complete recovery from PCOS signs and symptoms was obtained by treating animals with a daily supplementation of 420 mg/kg myo‐inositol and D‐chiro‐inositol (MyoIns/ DCIns) in a 40:1 molar ratio. Namely, ovaries from mice treated by this protocol recovered normal histological features and a proper ratio of theca/granulosa cell layer thickness (TGR), suggesting that the androgenic phenotype was efficiently reversed. Indeed, we identified TGR as a useful index of PCOS, as its increase in PCOS‐modeled mice correlated linearly with reduced reproductive capability (r=0.75, p<0.0001). Mice treated with a 40:1 formula regained low TGR values and faster recovery of their fertility, with a physiological delivery time after mating. On the other hand, a higher D‐chiro‐inositol treatment formula, such as MyoIns versus DCIns 5:1, was ineffective or even had a negative effect on clinical‐ pathological outcomes.
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.
Ageing and age-related diseases share some basic mechanistic pillars that largely converge on inflammation. During ageing, chronic, sterile, low-grade inflammation - called inflammaging - develops, which contributes to the pathogenesis of age-related diseases. From an evolutionary perspective, a variety of stimuli sustain inflammaging, including pathogens (non-self), endogenous cell debris and misplaced molecules (self) and nutrients and gut microbiota (quasi-self). A limited number of receptors, whose degeneracy allows them to recognize many signals and to activate the innate immune responses, sense these stimuli. In this situation, metaflammation (the metabolic inflammation accompanying metabolic diseases) is thought to be the form of chronic inflammation that is driven by nutrient excess or overnutrition; metaflammation is characterized by the same mechanisms underpinning inflammaging. The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products, contribute to circadian rhythms and crosstalk with other organs and systems. We argue that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing. Finally, we propose the use of new biomarkers (DNA methylation, glycomics, metabolomics and lipidomics) that are capable of assessing biological versus chronological age in metabolic diseases.
Rationale
The respective involvements of both the thalamus and exhibitionism in cerebral X-linked adrenoleukodystrophy (X-ALD) have not been reported.
Patient concerns
An 11-year-old boy initially presented with exhibitionism and progressive neurobehavioral symptoms. He subsequently developed transient urinary and fecal incontinence, and an unwillingness to eat or communicate.
Diagnoses
We conducted contrast-enhanced brain magnetic resonance imaging (MRI), which revealed symmetrical altered signal intensities in bilateral frontal white matter, the basal ganglia, and dorsal thalami, as well as a peripheral rim of contrast enhancement. Diagnosis of adolescent cerebral X-ALD was confirmed on the basis of next generation genetic sequencing analysis.
Interventions
We initiated the patient on hormonal replacement therapy.
Outcomes
We observed rapidly progressive neurologic deterioration in this patient, and the boy fell into a vegetative state 10 months after discharge.
Lessons
We recommend that physicians should not disregard X-ALD in patients with isolated psychiatric symptoms, including hypersexual behavior. The combination of detailed clinical evaluation, MRI, and next generation genetic sequencing can expedite the diagnostic process of atypical variant of X-ALD.
Objective:
Pretreatment of myoinositol is a very new method that was evaluated in multiple small studies to manage poor ovarian response in assisted reproduction. This study was to determine the efficacy of myoinositol supplement in infertile women undergoing ovulation induction for intracytoplasmic sperm injection (ICSI) or in vitro fertilization embryo transfer (IVF-ET).
Methods:
A meta-analysis and systematic review of published articles evaluating the efficacy of myo-inositol in patients undergoing ovulation induction for ICSI or IVF-ET was performed.
Results:
Seven trials with 935 women were included. Myoinositol supplement was associated with significantly improved clinical pregnancy rate [95% confidence interval (CI), 1.04-1.96; P = .03] and abortion rate (95% CI, 0.08-0.50; P = .0006). Meanwhile, Grade 1 embryos proportion (95% CI, 1.10-2.74; P = .02), germinal vescicle and degenerated oocytes retrieved (95% CI, 0.11-0.86; P = .02), and total amount of ovulation drugs (95% CI, -591.69 to -210.39; P = .001) were also improved in favor of myo-inositol. There were no significant difference in total oocytes retrieved, MII stage oocytes retrieved, stimulation days, and E2 peak level.
Conclusions:
Myoinositol supplement increase clinical pregnancy rate in infertile women undergoing ovulation induction for ICSI or IVF-ET. It may improve the quality of embryos, and reduce the unsuitable oocytes and required amount of stimulation drugs.
Objective:
Our study aims to demonstrate that the use in the preconceptional period until the 24th week of pregnancy of inositol and folic acid, first of all, preserves the product of conception from neural tube defects (NTDs) and then, thanks to inositol supplementation, it possibly counteracts and prevents the onset of maternal gestational diabetes (GDM).
Patients and methods:
We have collected data derived from pregnant women arrived at our laboratory, from January 2014 to January 2016, with no family history of type 2 diabetes and hypertension. The first group (n = 68 women) was treated from the preconceptional period until the 24th week of pregnancy with 1.75 g/day myo-inositol, 250 mg/day D-chiro-inositol, 12.5 mg/day Zinc pidolate, 100 mg/day methylsulfonylmethane, 120 mg/day Vitamin C and 400 mcg/day (6S)-5-methyltetrahydrofolic acid. The control group (n = 72) was only treated with 400 mcg/day folic acid. The main outcome measure was the prevalence of maternal GDM. Secondary outcome measures were the prevalence of NTDs and fetal macrosomia.
Results:
A significant difference was found regarding body mass index (BMI), fasting oral glucose tolerance test (OGTT), after 1-h-glucose OGTT, 2-h-glucose OGTT, glycated hemoglobin (HbA1c) and serum folate, between the two groups. Five infants, in the control group, weighted greater than 4 kg. Moreover, we found a positive correlation between HbA1c and OGTT at the 24th week of pregnancy.
Conclusions:
This study shows the efficacy of preconceptional supplementation of inositol to reduce the risk of the onset of GDM and to confirm the importance of folic acid supplementation to avoid NTDs development. Moreover, the positive correlation between HbA1c and OGTT may be useful to consider the use of HbA1c as a single tool for GDM prevention and diagnosis in selected woman in pregnancy.
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disease that involves menstrual dysfunction and reproductive difficulty, as well as metabolic problems. The aim of this study was to assess the effectiveness of myo-inositol (MYO) and d-chiro-inositol (DCI) on improving oocyte or embryo quality and pregnancy rates for women with PCOS undergoing intracytoplasmic sperm injection (ICSI). We searched the Web of Knowledge, MEDLINE, EMBASE, Pubmed, Scopus and Cochrane databases for all articles published in any language up to March 2017. The selection criteria were as follows: (population) patients with PCOS; (intervention) treatment with inositol (MYO, DCI, or both, with any dose and any duration) in conjunction with an ovulation-inducing agent versus the ovulation-inducing agent alone; (outcome) oocyte and embryo quality; (study design) randomized controlled trials. Of 76 identified studies, eight RCTs were included for analysis comprising 1019 women with PCOS. MYO supplementation was insufficient to improve oocyte quality (OR 2.2051; 95% CI 0.8260 to 5.8868), embryo quality (OR 1.6231, 95% CI 0.3926 to 6.7097), or pregnancy rate (OR 1.2832, 95% CI 0.8692 to 1.8944). Future studies of appropriate dose, size and duration of DCI are vital to clarify its the role in the management of PCOS.
Abstract. The aim of the present study was to demonstrate that the use of inositol and folic acid from the first trimester of pregnancy, counteracts the onset of gestational diabetes mellitus (GDM) in women at risk, preserving the infants from macrosomia, hypoglycemia and preterm delivery. The authors collected data from the pregnant women at the laboratory (Unit of Cytogenic and Molecular Genetics), from January 2014 to April 2016, all with first trimester fasting plasma glucose (FPG) >92 mg/dl. A total of 40 women were treated with 250 mg/day D chiro inositol, 1.75 g/day D myo inositol, 12.5 mg/day zinc, 10 mg/day methylsulfo¬nylmethane, 400 μg/day 5 methyltetrahydrofolic acid. The other 43 women (control group) were treated with only 400 μg/day folic acid. The primary outcome measure was the incidence of maternal GDM. The secondary outcome measures were the incidence of fetal macrosomia, preterm delivery and neonatal hypoglycemia. At the 24th week of pregnancy, the incidence of maternal GDM was recorded in 18 women in the control group and in 5 women in the treated group [relative risk (RR)=3.35; 95% confidence interval (CI)=1.37 8.17; P=0.0028). A significant difference was observed between treated and control groups in terms of risk of macrosomia. A total of seven infants in the control group, and two in the treated group, weighed >4,000 g (RR=5,12; 95% CI=1.21 21.68; P=0.0099). No significant difference was identified between two groups, regarding the other two secondary outcomes, neonatal hypoglycemia (RR=4.650; 95% CI=0.57 38.11; P=0.1086) and preterm delivery (RR=1.74; 95% CI=0.83 3.66; P=0.1301). The current study demonstrated the potential benefit of supplementation with the association of D chiro inositol and D myo inositol in pregnant ‘at risk’ women, with first trimester FPG >92 mg/dl, in preventing the onset of maternal GDM and macrosomia in newborns.
Methods:
A total of 196 infertile patients diagnosed with PCOS and admitted to Dokuz Eylul University Faculty of Medicine were included in the study between March 2013 and May 2016. The patients in group 1 (n = 98) were given 4 g MYO and 400 μg folic acid before and during ovulation induction. The patients undergone controlled ovarian hyperstimulation (COH) with recombinant FSH and IUI. The patients in group 2 (n = 98), were given recombinant FSH directly and 400 μg folic acid. The primary outcome measure of this study was the clinical pregnancy rate.
Results:
In group 1, 9 patients conceived spontaneous pregnancy. During COH + IUI treatment three cycles were canceled in group 1 and 8 cycles in group 2. Total rFSH dose and cycle duration were significantly lower and clinical pregnancy rates were higher in group 1. The pregnancy rate for group 1 was %18.6 and for group 2 was %12.2. Conclusıons: This study shows that MYO should be considered in the treatment of infertile PCOS patients. MYO administration increases clinical pregnancy rates, lowers total rFSH dose and the duration of the ovulation induction.
The use of folic acid in the periconceptional period can prevent about 70% of neural tube defects (NTDs). In the remaining cases, no medical prevention is available, and those conditions should be defined as folate-resistant NTDs. Rodent models suggest that some folate-resistant NTDs can be prevented by inositol (myoinositol and chiroinositol) supplementation prior to pregnancy. Should folic acid be combined with myoinositol periconceptional supplementation to reduce the overall risk of NTDs even in humans? Hereafter, we discuss the results from the PONTI study that strongly support both the effectiveness and safety of myoinositol periconceptional supplementation in preventing human NTDs. We further report on the largest case series of pregnancies treated with myoinositol and folic acid. At our institution, a sequential study during 12 years involved mothers at risk of fetal NTDs, and 29 babies from 27 pregnancies were born after periconceptional combined myoinositol and folic acid supplementation. No case of NTDs was observed, despite the high recurrence risk in the mothers. Taken together, those data suggest that periconceptional folic acid plus myoinositol can reduce both the occurrence and recurrence risks of NTDs in a greater number of cases than folic acid alone.
[This corrects the article DOI: 10.1155/2016/3058393.].
Background:
Maternal mental disorders are considered a leading complication of childbirth and a common contributor to maternal death. In addition to undermining maternal welfare, untreated postpartum psychopathology can result in child emotional and physical neglect, and associated significant pediatric health costs. Some women may experience a traumatic childbirth and develop posttraumatic stress disorder (PTSD) symptoms following delivery (CB-PTSD). Although women are routinely screened for postpartum depression in the U.S., there is no recommended protocol to inform the identification of women who are likely to experience CB-PTSD. Advancements in computational methods of free text has shown promise in informing diagnosis of psychiatric conditions. Although the language in narratives of stressful events has been associated with post-trauma outcomes, whether the narratives of childbirth processed via machine learning can be useful for CB-PTSD screening is unknown.
Objective:
This study examined the utility of written narrative accounts of personal childbirth experience for the identification of women with CB-PTSD. To this end, we developed a model based on natural language processing (NLP) and machine learning (ML) algorithms to identify CB-PTSD via classification of birth narratives.
Study design:
A total of 1,127 eligible postpartum women who enrolled in a study survey during the COVID-19 era provided short written childbirth narrative accounts in which they were instructed to focus on the most distressing aspects of their childbirth experience. They also completed a PTSD symptom screen to determine CB-PTSD. After exclusion criteria were applied, data from 995 participants was analyzed. An ML-based Sentence-Transformer NLP model was used to represent narratives as vectors that served as inputs for a neural network ML model developed in this study to identify participants with CB-PTSD.
Results:
The ML model derived from NLP of childbirth narratives achieved good performance: AUC 0.75, F1-score 0.76, sensitivity 0.8, and specificity 0.70. Moreover, women with CB-PTSD generated longer narratives (t-test results: t=2.30, p=0.02) and used more negative emotional expressions (Wilcoxon test: 'sadness': p=8.90e-04, W=31,017; 'anger': p=1.32e-02, W=35,005.50) and death-related words (Wilcoxon test: p=3.48e-05, W=34,538) in describing their childbirth experience than those with no CB-PTSD.
Conclusions:
This study provides proof of concept that personal childbirth narrative accounts generated in the early postpartum period and analyzed via advanced computational methods can detect with relatively high accuracy women who are likely to endorse CB-PTSD and those at low risk. This suggests that birth narratives could be promising for informing low-cost, non-invasive tools for maternal mental health screening, and more research that utilizes ML to predict early signs of maternal psychiatric morbidity is warranted.
Background
Evidence that nutritional supplementation before and during pregnancy improves peripartum outcomes is sparse. In the Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR) trial we previously reported that a combined myo-inositol, probiotics and micronutrient supplement starting preconception showed no difference in the primary outcome of gestational glycemia, but did reduce the risk of preterm delivery, preterm pre-labor rupture of membranes and major postpartum hemorrhage.
Objective
To examine the hypothesis that a reduction in major postpartum hemorrhage following a combined nutritional (myo-inositol, probiotics and micronutrient) intervention is linked with promotion of labor progress and reduced operative delivery.
Study Design
This double-blind randomized controlled trial recruited from the community 1729 UK, Singapore and New Zealand women aged 18-38 years planning conception between 2015-2017. Here, the effects of the nutritional intervention compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy, on the secondary outcomes of peripartum events were examined using multinomial, Poisson and linear regression adjusting for site, ethnicity and important covariates.
Results
Of the women who conceived and progressed beyond 24 weeks’ gestation with a singleton pregnancy (n=589), 583 (99%) provided peripartum data. Between women in the intervention (n=293) and control (n=290) groups, there were no differences in rates of labor induction, oxytocin augmentation during labor, instrumental delivery, perineal trauma and intrapartum cesarean section. While duration of the first stage of labor was similar, the second-stage duration was 20% shorter in the intervention group compared with controls [adjusted mean difference -12.0 (95%CI -22.2, -1.2) minutes, p=0.029], accompanied by a reduction in operative delivery for delayed second-stage progress [adjusted risk ratio 0.61 (0.48, 0.95); p=0.022]. Estimated blood loss was 10% less with intervention compared with control [adjusted mean difference -35.0 (-70.0, -3.5) ml, p=0.047], consistent with previous findings of reduced postpartum hemorrhage.
Conclusion
Supplementation with a specific combination of myo-inositol, probiotics and micronutrients starting preconception and continued in pregnancy reduced both the duration of the second stage of labor and the risk of operative delivery for delay in the second stage, and reduced blood loss at delivery.
Objective:
Better preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited.
Research design and methods:
This double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18-38 years planning conception. We investigated whether a nutritional formulation containing myo-inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test).
Results:
Between 2015 and 2017, participants were randomized to control (n = 859) or intervention (n = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified P < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (β [95% CI] loge mmol/L intervention vs. control -0.004 [-0.018 to 0.011], 0.025 [-0.014 to 0.064], 0.040 [0.004-0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92-1.62]), birth weight (adjusted β = 0.05 kg [-0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted β = 0.20 [-0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22-0.82]), adjusting for prespecified covariates.
Conclusions:
Supplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth.
Objective
To compare efficacy of myoinositol as an adjuvant to dietary modification for treatment of gestational diabetes mellitus in Asian Indian women compared to controls.
Study Design
Setting: This pilot randomized open label trial was conducted in a single antenatal clinic in India. Subjects: One hundred women with singleton pregnancy and gestational diabetes diagnosed between 14-28 weeks’ gestation were included. Overt diabetes, twin pregnancy, pre-existing renal disease, heart disease and other chronic medical disorders were exclusions. Intervention: Participants were randomized in two groups (1:1 ratio) by opaque envelope method. Individualized nutrition counseling with dietary modification and routine antenatal care was provided to all. Fifty women received myoinositol 1000 mg twice daily; 50 controls did not receive myoinositol. Fasting and postprandial glucose levels were assessed after two weeks. Women not achieving glycemic targets (fasting glucose <95 and postprandial glucose <120 mg/dL) were given pharmacologic therapy. Contributory factors in women requiring additional pharmacologic therapy, maternal and fetal outcomes were noted. Statistical analysis: Between group comparisons reported relative risk and mean difference. To assess predictive factors for need for pharmacologic therapy, univariate and multivariable logistic regression analysis were used.
Results
Baseline characteristics were comparable in both groups. One woman in the myoinositol group, otherwise all women provided glycaemia data throughout their pregnancy. Glycaemic control was achieved in 44/ 49 (89.8%) women in myoinositol group which was significantly higher than 34/50 (68%) in the controls ((relative risk 0.31, 95% confidence interval 0.13 to 0.80, p = 0.008). Mean duration of myoinositol treatment was 17.6 weeks (standard deviation 5.3). Additional treatment with metformin/insulin was needed in all women failing to achieve glycaemic control. The mean (range) dose of insulin was 25.3 units in myoinositol group compared to 14.27 units in controls (p = 0.058). Secondary outcomes were similar in two groups except baby weight which was higher in controls (p = 0.018).
Conclusions
Oral supplementation with myoinositol in dose of 1 gm twice-daily, when started soon after the diagnosis of GDM, is effective in achieving glycemic control and decreasing the need for additional pharmacological therapy in Asian Indian women.
Trial Registration
Clinical Trial Registry of India CTRI2018/05/013937
Objective:
The aim of this clinical trial was to evaluate the efficacy of seven different ratios between two inositols stereoisomers, myo-inositol (MI) and D-chiro-inositol (DCI), in the therapy of polycystic ovary syndrome (PCOS).
Patients and methods:
fifty-six PCOS patients (8 for each group) were treated by oral route using the following formulations: DCI alone, and 1:3.5; 2.5:1; 5:1; 20:1; 40:1, 80:1 MI/DCI ratio. They received 2 g of inositols twice a day for 3 months. The primary outcome was ovulation, the secondary outcome included the improvement of FSH, LH, Sex Hormone Binding Globulin (SHBG), 17-beta-Estradiol (E2), free testosterone, basal and postprandial insulin levels, as well as HOMA index, BMI and menses.
Results:
We found that the 40:1 MI/DCI ratio is the best for PCOS therapy aimed at restoring ovulation and normalizing important parameters in these patients. The other formulations were less effective. In particular, a decreased activity was observed when the 40:1 ratio was modified in favour of DCI.
Conclusions:
Our data demonstrated that DCI activity is beneficial mainly at a specific ratio with MI, whereas the increase of DCI causes the loss of the beneficial effects at reproductive level. These results in humans validate a previous preclinical study with different MI/DCI ratios carried out in an experimental model of PCOS mice.
This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and d-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle-stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. Moreover, MI enhances the effect of metformin and clomiphene on the fertility of PCOS women seeking pregnancy. As impaired intestinal transport may lead to unsuccessful inositol treatment, we also discuss new data on the use of alpha-lactalbumin to boost inositol absorption. Overall, the physiological activities of MI and DCI dictate the dosages and timing of inositol supplementation in the treatment of PCOS.
Objective:
To evaluate, in overweight/obese PCOS women, which of three distinct treatment modalities achieved the greatest clinical benefits in terms of clinical and body composition outcomes.
Patients and methods:
Forty-three polycystic ovary syndrome (PCOS) overweight/obese patients were randomly treated for 6 months with: only diet (Group 1, n = 21); diet and myo-inositol (MI) 4 g + folic acid 400 µg daily (group 2, n = 10); diet in association with MI 1.1 g + D-chiroinositol (DCI) 27.6 mg + folic acid 400 µg daily (group 3, n = 13). Menstrual cycle, Ferriman-Gallwey score, body mass index (BMI), waist circumference, hip circumference, waist-hip ratio (WHR), and body composition by bioimpedentiometry were measured at baseline, 3 and 6 months.
Results:
Body weight, BMI, waist and hip circumferences decreased significantly in all groups. There was a significant difference between the 3 groups regarding the restoration of menstrual regularity (p = 0.02) that was obtained in all patients only in-group 3.
Conclusions:
MI+DCI in association with diet seems to accelerate the weight loss and the fat mass reduction with a slight increase of percent lean mass, and this treatment contributes significantly in restoring the regularity of the menstrual cycle.
Background:
Subfertile women are highly motivated to try different adjunctive therapies to have a baby, and the widespread perception is that dietary supplements such as myo-inositol (MI) and D-chiro-insoitol (DCI) are associated with only benefit, and not with harm. Many fertility clinicians currently prescribe MI for subfertile women with polycystic ovary syndrome (PCOS) as pre-treatment to in vitro fertilisation (IVF) or for ovulation induction; however no high-quality evidence is available to support this practice. This review assessed the evidence for the effectiveness of inositol in subfertile women with a diagnosis of PCOS.
Objectives:
To evaluate the effectiveness and safety of oral supplementation of inositol for reproductive outcomes among subfertile women with PCOS who are trying to conceive.
Search methods:
We searched the following databases (to July 2018): Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. We also checked reference lists and searched the clinical trials registries.
Selection criteria:
We included randomised controlled trials (RCTs) that compared any type, dose, or combination of oral inositol versus placebo, no treatment/standard treatment, or treatment with another antioxidant, or with a fertility agent, or with another type of inositol, among subfertile women with PCOS.
Data collection and analysis:
Two review authors independently selected eligible studies, extracted data, and assessed risk of bias. The primary outcomes were live birth and adverse effects; secondary outcomes included clinical pregnancy rates and ovulation rates. We pooled studies using a fixed-effect model, and we calculated odds ratios (ORs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence by applying GRADE criteria.
Main results:
We included 13 trials involving 1472 subfertile women with PCOS who were receiving myo-inositol as pre-treatment to IVF (11 trials), or during ovulation induction (two trials). These studies compared MI versus placebo, no treatment/standard, melatonin, metformin, clomiphene citrate, or DCI. The evidence was of 'low' to 'very low' quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency, and lack of reporting of clinically relevant outcomes such as live birth and adverse events.We are uncertain whether MI improves live birth rates when compared to standard treatment among women undergoing IVF (OR 2.42, 95% CI 0.75 to 7.83; P = 0.14; 2 RCTs; 84 women; I² = 0%). Very low-quality evidence suggests that for subfertile women with PCOS undergoing pre-treatment to IVF who have an expected live birth rate of 12%, the rate among women using MI would be between 9% and 51%.We are uncertain whether MI may be associated with a decrease in miscarriage rate when compared to standard treatment (OR 0.40, 95% CI 0.19 to 0.86; P = 0.02; 4 RCTs; 535 women; I² = 66%; very low-quality evidence). This suggests that among subfertile women with PCOS with an expected miscarriage rate of 9% who are undergoing pre-treatment to IVF, the rate among women using MI would be between 2% and 8%; however this meta-analysis is based primarily on one study, which reported an unusually high miscarriage rate in the control group, and this has resulted in very high heterogeneity. When we removed this trial from the sensitivity analysis, we no longer saw the effect, and we noted no conclusive differences between MI and standard treatment.Low-quality evidence suggests that MI may be associated with little or no difference in multiple pregnancy rates when compared with standard treatment (OR 1.04, 95% CI 0.63 to 1.71; P = 0.89; 2 RCTs; 425 women). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected multiple pregnancy rate of 18%, the rate among women using inositol would be between 12% and 27%.We are uncertain whether MI may be associated with an increased clinical pregnancy rate when compared to standard treatment (OR 1.27, 95% CI 0.87 to 1.85; P = 0.22; 4 RCTs; 535 women; I² = 0%; very low-quality evidence). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected clinical pregnancy rate of 26%, the rate among women using MI would be between 24% and 40%. Ovulation rates were not reported for this comparison.Other comparisons included only one trial in each, so for the comparisons MI versus antioxidant, MI versus an insulin-sensitising agent, MI versus an ovulation induction agent, and MI versus another DCI, meta-analysis was not possible.No pooled evidence was available for women with PCOS undergoing ovulation induction, as only single trials performed comparison of the insulin-sensitising agent and the ovulation induction agent.
Authors' conclusions:
In light of available evidence of very low quality, we are uncertain whether MI improves live birth rate or clinical pregnancy rate in subfertile women with PCOS undergoing IVF pre-treatment taking MI compared to standard treatment. We are also uncertain whether MI decreases miscarriage rates or multiple pregnancy rates for these same women taking MI compared to standard treatment. No pooled evidence is available for use of MI versus placebo, another antioxidant, insulin-sensitising agents, ovulation induction agents, or another type of inositol for women with PCOS undergoing pre-treatment to IVF. No pooled evidence is available for use of MI in women undergoing ovulation induction.
Objective: To identify the effects of different dietary inositol stereoisomers on insulin resistance and the development of gestational diabetes mellitus (GDM) in women at high risk for this disorder.
Design: A preliminary, prospective, randomized, placebo controlled clinical trial.
Participants: Nonobese singleton pregnant women with an elevated fasting glucose in the first or early second trimester were studied throughout pregnancy.
Intervention: Supplementation with myo-inositol, d-chiro-inositol, combined myo- and d-chiro-inositol or placebo.
Main outcome measure: Development of GDM on a 75 grams oral glucose tolerance test at 24–28 weeks’ gestation. Secondary outcome measures were increase in BMI, need for maternal insulin therapy, macrosomia, polyhydramnios, neonatal birthweight and hypoglycemia.
Results: The group of women allocated to receive myo-inositol alone had a lower incidence of abnormal oral glucose tolerance test (OGTT). Nine women in the control group (C), one of the myo-inositol (MI), five in d-chiro-inositol (DCI), three in the myo-inositol/D-chiro-inositol group (MI/DCI) required insulin (p = .134). Basal, 1-hour, and 2 hours glycemic controls were significantly lower in exposed groups (p < .001, .011, and .037, respectively). The relative risk reduction related to primary outcome was 0.083, 0.559, and 0.621 for MI, DCI, and MI/DCI groups.
Conclusions: This study compared the different inositol stereoisomers in pregnancy to prevent GDM. Noninferiority analysis demonstrated the largest benefit in the myo-inositol group. The relevance of our findings is mainly related to the possibility of an effective approach in GDM. Our study confirmed the efficacy of inositol supplementation in pregnant women at risk for GDM.
Background:
Gestational Diabetes Mellitus (GDM) is defined as carbohydrate intolerance that; begins or it is first recognized during pregnancy. Insulin sensitizing substances as Myo-inositol have been considered for the prevention of GDM and related complications.
Objective:
Since previous studies failed to show a clear reduction of GDM complications, the aim of this study was to evaluate clinical and metabolic outcomes in women at risk for gestational diabetes mellitus supplemented with myo-inositol since first trimester.
Methods:
A secondary analysis of databases from 3 randomized, controlled trials (595 women enrolled), in which women at risk for GDM (a parent with type 2 diabetes, obese or overweight) were supplemented with myo-inositol (4g/day) throughout pregnancy. Main measures were the rate of adverse clinical outcomes: macrosomia (birth weight ≥ 4000 g), Large for Gestational Age babies (fetal growth ≥ 90° centile), Fetal Growth Restriction (fetal growth ≤ 3° percentile), pre-term birth (delivery before the 37° week since the last menstruation), gestational hypertension and GDM.
Results:
A significant reduction was observed for pre-term birth (10/291, 3.4% vs 23/304, 7.6%, p=0.03), macrosomia (6/291, 2.1% vs 16/304, 5.3%, p=0.04), LGA babies (14/291, 4.8% vs 27/304, 8.9 %,p=0.04) with only a trend to significance for gestational hypertension (4/291, 1.4% vs 12/304, 3.9%, p=0.07). GDM diagnosis was also decreased when compared to control group (32/291, 11.0% vs 77/304, 25.3%, p<0.001). At univariate logistic regression analysis myo-inositol treatment reduced the risk for pre-term birth (OR 0.44, CI 0.20 - 0.93), macrosomia (OR 0.38, CI 0.14 - 0.98) and GDM diagnosis (OR 0.36, CI 0.23 - 0.57).
Conclusion:
Myo-inositol treatment in early pregnancy is associated with a reduction in the rate of GDM and in the risk of preterm birth and macrosomia in women at risk for GDM.
AimsGestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy. The aim of the study is to compare the effect of different dosages of inositol stereoisomers supplementation on insulin resistance levels and several maternal-fetal outcomes in GDM women. Methods
Participants were randomly allocated to receive daily: 400 mcg folic acid (control treatment), 4000 mg myo-inositol plus 400 mcg folic acid (MI treatment), 500 mg d-chiro-inositol plus 400 mcg folic acid (DCI treatment) or 1100/27.6 mg myo/d-chiro-inositol plus 400 mcg folic acid (MI plus DCI treatment). The homeostasis model assessment of insulin resistance (HOMA-IR) was measured at the diagnosis of GDM and after 8 weeks of treatment. Secondary outcomes, obstetric outcomes and any maternal or fetal complication at delivery were also collected. ResultsEighty GDM women were assigned to one of the four arms of study (20 per arm). A significant delta decrease in HOMA-IR index was found in subjects of MI group without insulin therapy compared to control group (p < 0.001). A lower variation in average weight gain (at delivery vs pre-pregnancy and OGTT period) was detected in MI group vs control group (p = 0.001 and p = 0.019, respectively). Moreover, women exposed to MI and MI plus DCI required a significantly lower necessity of an intensified insulin treatment. Women of the control group had newborns with higher birth weight compared with women treated with inositol (p = 0.032). Conclusions
Our study provides interesting but preliminary results about the potential role of inositol stereoisomers supplementation in the treatment of GDM on insulin resistance levels and several maternal-fetal outcomes. Further studies are required to examine the optimal and effective dosages of different inositol supplements. Clinical trial reg. no.NCT02097069, ClinicalTrial.gov.
Objective:
It was previously shown that higher concentrations of myo-inositol in human follicular fluid improve oocyte and embryo quality, whereas D-chiro-inositol seems to worsen oocyte quality and ovarian response in polycystic ovary syndrome patients. Our study was the first one aiming to test whether different myo-inositol and D-chiro-inositol concentration in follicular fluids correlate with blastocyst quality in healthy young women.
Patients and methods:
Eight egg donors and eleven couples undergoing in vitro fertilization, were involved in a prospective observational study. Myo-inositol/D-chiro-inositol ratio was calculated in the follicular fluids and associated with different blastocyst grades. Donors were homogeneous and followed the same standard stimulation protocol.
Results:
The ratio between myo-inositol and D-chiro-inositol was significantly higher in the specimens rated as good quality blastocysts, compared to those rated as poor-quality blastocysts. In this study, almost all the transferred blastocysts were graded as good quality and were correlated to lower D-chiro-inositol content in the follicular fluid; the implantation rate and pregnancy rate were satisfying. Our data suggest that the reduction of such ratio in follicular fluid seems to play a negative role in follicular development.
Conclusions:
We found a correlation between myo-inositol/D-chiro-inositol ratio in follicular fluid and blastocyst quality. The value of this ratio may represent a new biomarker for estimating the good features of blastocysts, and a prognostic factor of embryo implantation and pregnancy success. Moreover, the pre-treatment with myo-inositol in women undergoing in vitro fertilization (IVF) may improve oocyte quality and ART outcome.
Clinical trial registration number:
NCT03055442 (ClinicalTrials.gov registry).
Objectives:
This study investigated if inositol in a combination of myo-inositol and D-Chiro-inositol would prevent gestational diabetes mellitus (GDM) in women with a family history of diabetes.
Research design and methods:
This was a randomized controlled trial that examined whether inositol from the first antenatal visit prevents GDM. The trial was carried out in a single-center tertiary referral center. Women with a family history of diabetes were enrolled at the first antenatal visit. They were randomized to the intervention group, who received a combination of 1,100 mg myo-inositol, 27.6 g D-Chiro inositol, and 400 mcg folic acid, or to the control group, who received 400 mcg folic acid only. All women had an oral glucose tolerance test between 24 and 28 weeks gestation. The primary end point was the incidence of GDM. Statistical analysis was carried out using SPSS Statistical Package version 20.
Results:
Two hundred forty women, 120 in each arm, were recruited between January 2014 and July 2015. There were no differences in characteristics between the groups. The incidence of GDM was 23.3% (n = 28) in the intervention group compared with 18.3% (n = 22) in the control group (P = 0.34). The mean fasting plasma glucose at the glucose tolerance test was 81 mg/dL in both groups.
Conclusions:
Commencing an inositol combination in early pregnancy did not prevent GDM in women with a family history of diabetes. Further studies are required to examine whether inositol supplements at varying doses may prevent GDM.
Insulin resistance (IR) plays a pivotal role in PCOS. Insulin-sensitizer agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS. The purpose of this study is to compare their effects on the clinical and metabolic features of the women with PCOS. Fifty PCOS women with IR and/or hyperinsulinemia were randomized to treatment with metformin (1500 mg/day) or myo-inositol (4 g/day). IR was defined as HOMA-IR >2.5, while hyperinsulinemia was defined as a value of AUC for insulin after a glucose load over the cutoff of our laboratory obtained in normal women. The Matsusa Index has been calculated. The women have been evaluated for insulin secretion, BMI, menstrual cycle length, acne and hirsutism, at baseline and after 6 months of therapy. The results obtained in both groups were similar. The insulin sensitivity improved in both treatment groups. The BMI significantly decreased and the menstrual cycle was normalized in about 50% of the women. No significant changes in acne and hirsutism were observed. The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.