Effect of Oral High Molecular Weight Hyaluronic Acid (HMWHA), Alpha Lipoic Acid (ALA), Magnesium, Vitamin B6 and Vitamin D Supplementation in Pregnant Women: A Retrospective Observational Pilot Study.

Background-Pregnancy represents a nutritional challenge, since macro- and micronutrients intake can affect mother' health and influence negative outcomes. The aim of this retrospective pilot study is to evidence whether the oral supplementation with high molecular weight hyaluronic acid (HMWHA), in association with alpha lipoic acid (ALA), magnesium, vitamin B6 and vitamin D, in pregnant women, could reduce adverse effects, such as PTB, pelvic pain, contraction and hospitalization. Methods-Data were collected from n = 200 women treated daily with oral supplements of 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6 and 50 mcg vitamin D (treatment group) and from n = 50 women taking with oral supplements of 400 mg magnesium (control group). In both groups, supplementation started from the 7th gestational week until delivery. Results-Oral treatment with HMWHA, in association with ALA, magnesium, vitamin B6 and vitamin D in pregnant women, significantly reduced adverse events, such as PTB (p < 0.01), pelvic pain and contractions (p < 0.0001), miscarriages (p < 0.05) and admission to ER/hospitalization (p < 0.0001) compared with the control group. Conclusions-Despite HMWHA having been poorly used as a food supplement in pregnant women, our results open a reassuring scenario regarding its oral administration during pregnancy.

Long-Lasting Therapies with High Doses of D-chiro-inositol: The Downside.

Background: Recent studies reported possible concerns following long-lasting treatments with high doses of D-chiro-inositol in women. However, to date, no clinical trial has investigated or validated these concerns. We addressed this issue both retrospectively and with a prospective pilot study. Methods: For the retrospective analysis, we searched our databases for insulin-resistant women who took 1200 mg/day D-chiro-inositol for 6 months. In our prospective study, we enrolled 10 healthy women to supplement with the same therapeutic scheme. We performed statistical analyses through the Wilcoxon Signed-Rank Test. A p-value < 0.05 was considered significant. Results: Twenty women underwent 6 months of 1200 mg/day D-chiro-inositol. The treatment significantly decreased BMI, glycemia, insulinemia, HOMA-IR, serum levels of LH, total testosterone, and DHEAS. Serum estradiol rose and menstrual abnormalities occurred following the treatment. In our prospective study, we observed increases in serum levels of total testosterone and asprosin in healthy women. Conclusions: This is the first clinical evidence demonstrating that long-term treatments with high dosages of D-chiro-inositol can predispose women to hormonal and menstrual abnormalities. Moreover, the accumulation of D-chiro-inositol following such treatment regimen may lead to detrimental effects in non-reproductive tissues, as demonstrated by the increase in asprosin levels.

D-chiro-inositol Induces Ovulation in Non-Polycystic Ovary Syndrome (PCOS), Non-Insulin-Resistant Young Women, Likely by Modulating Aromatase Expression: A Report of 2 Cases.

BACKGROUND Anovulation consists in the lack of oocyte release during the menstrual cycle, leading to an irregular menstrual cycle. Untreated chronic anovulation is one of the major causes of female infertility and can induce hypoestrogenism. Different etiological factors can contribute to anovulation; therefore, the clinical approaches to manage this condition should take into account the specific patient characteristics. Oral ovulation-inducing agents are first-line treatments for most anovulatory patients. Drugs used include selective estrogen receptor modulators (SERMs) such as clomiphene citrate and aromatase inhibitors (AIs) such as letrozole. The latter, in particular, halts the estrogen biosynthesis by blocking the activity of steroidogenic enzyme aromatase, which catalyzes the conversion of androgens to estrogens. Similarly, d-chiro-inositol (DCI) modulates the activity of aromatase by reducing the corresponding gene expression, and DCI supplementation was successfully used to induce ovulation in anovulatory PCOS patients. Here, we report the use of DCI to induce ovulation in non-PCOS anovulatory oligomenorrheic women. CASE REPORT Two young non-PCOS anovulatory oligomenorrheic women received treatment with high-dose (1200 mg) DCI for 6 weeks. Based on an initial evaluation, both patients had normal hormone levels and were non-insulin-resistant. Ovulation assessment was based on the increment of progesterone and LH levels, as well as on the endometrial thickening. Also, the treatment with DCI resulted in a reduction of testosterone levels relative to baseline values. CONCLUSIONS After the 6-week treatment with 1200 mg DCI, ovulation was restored in both women, as confirmed by increased progesterone and LH and endometrial thickening.

Positive effect of a new supplementation of vitamin D3 with myo-inositol, folic acid and melatonin on IVF outcomes: a prospective randomized and controlled pilot study.

To assess whether oral supplementation of vitamin D3, myo-inositol, folic acid and melatonin affects IVF outcomes. One hundred and twenty consecutive infertile women attending IVF treatment were 1:1 randomly distributed in two groups. Women in group A (control) were assigned to receive myo-inositol, alpha-lactalbumin and folic acid in the morning, and myo-inositol, folic acid and melatonin in the evening. Women in group B (treated) were assigned to receive analogous treatment, with the addition of cholecalciferol (vitamin D3) in the evening from the early beginning of the luteal phase. 50 patients in group A and 50 in group B underwent blastocyst transfer and were considered in the statistical analysis. Vitamin D3 levels significantly increased after 45 days of treatment: 33.2 ng/ml in group B Vs. 24.3 ng/ml in group A (p < .0001). The implantation rate increased as well: 37.1% in group B Vs. 19.2% in group A (p < .0151). Overall, the results indicate that increased vitamin D3 levels positively correlate with the implantation rate in IVF. Because of the low number of participants, these findings need to be confirmed with larger cohorts of patients.