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Introduction and purpose Polycystic ovary syndrome is a common reproductive disorder, accompanied primarily by hyperandrogenism and insulin resistance. Myo-inositol (MI) and D-chiro-inositol (DCI), have emerged as potential therapeutic agents due to their role as insulin sensitizers. This article examines the effects of inositol therapy on fertility in women with PCOS and its role in assisted reproductive technology (ART). Studies suggest that inositols alleviate irregular menstruation, reduce androgen levels and positively affect ovulation rates. MI supplementation has also shown positive effects during controlled ovarian hyperstimulation and IVF procedures, reducing the required FSH dose and cycle length. However, despite positive results on ovulation and menstrual regularity, the article indicates the need for further studies to establish inositol as standard ART therapy in patients with PCOS. Material and methods The following review was based on articles from the PubMed and Google Scholar databases. Key search terms included polycystic ovary syndrome; assisted reproductive treatment, insulin resistance, inositols, Myo-inositol, D-chiro-inositol. Conclusions Inositols are a promising therapeutic option for women with PCOS. They have been shown to have positive effects on improving insulin sensitivity and fertility. However, despite inositol's safety and easy availability, the ideal dose and timing of use, the appropriate MI/DCI ratio, as well as the potential side effects of excess DCI and the problem of inositol resistance, require further comprehensive studies.

Despite the chemical similarities between myo-inositol and D-chiro-inositol and their synergistic effects on insulin sensitivity, they serve different functions. Insulin resistance is one of the etiological factors in the development of polycystic ovary syndrome (PCOS), diabetes mellitus, metabolic syndrome, infertility, menstrual irregularities and ovulation disorders, pregnancy complications, in particular, gestational diabetes. Myo-inositol plays an important role in the insulin transfer and hormone synthesis in the ovaries, in oocyte maturation, fertilization, implantation and post-implantation development. Many studies confirm the positive effect of inositol isomers on metabolic, hormonal and reproductive disorders, both in the form of monotherapy and in combination with other drugs to enhance the therapeutic effect and bioavailability. Myo-inositol has a favorable safety profile. Studies have shown that in patients with PCOS myo-inositol improves ovarian function and fertility, reduces the manifestations of hyperandrogenism, insulin resistance and normalizes weight. Myo-inositol and D-chiro-inositol have different mechanisms of action on insulin sensitivity and have different functions. The balance of the two isomers ensures the normal secretion of hormones and ovarian functioning, but it is currently unknown what the optimal ratio of these two isomers due to the small number of high quality studies and the difficulty of studying their isolated action. There are currently different combinations of myo- and D-chiro-inisotol, but they also have not been supported by enough high quality studies. When prescribing various isomers of inositol, it should be remembered that doses above 4000 mg are the most studied in patients with PCOS, but D-chiro-inositol concentration above 1200 mg/day has undesirable effects. Most studies indicate that D-chiro-inositol value is increased in PCOS, therefore oocytes are more sensitive to its overdose, and combination drugs require more study. Currently, there is no consensus in the literature on the advantage of combined supplements of myo- and D-chiro-inositol compared to monotherapy with myo-inositol. Today, myo-inositol monotherapy is more researched and safer.

Introduction: Myo-inositol (MYO) and D-chiro-inositol are chemical compounds known to exert an impact on multiple signaling pathways of a human body. Due to its effects on insulin metabolism and ovaries’ hormone activity their use in polycystic ovary syndrome (PCOS) therapies has been highly recommended in the recent literature. In this article we aim to review the known and possible applications of inositol and its derivatives for treatment of various gynecological and endocrine disorders and to indicate possible directions of further investigations. Methods and materials: This article is based on the literature found in PubMed Database from the period of 2016-2022 with use of keywords such as “inositol”; “myoinositol”; “d-chiro-inositol”; “PCOS”; “insulin”. Results: The applications of myoinositol in the treatment of polycystic ovary syndrome (PCOS) are very well known in recent publications. It is reported that MYO supplementation improves the quality of oocytes, regulates the menstrual cycle and ovulation rates. Prevention of gestational diabetes (GDM) amongst the patients with risk factors is likely another use of inositols. Inositol takes part in phospholipase C pathway, thus its depletion may be the cause for hypothyroidism. Inositol inhibits the expression of aromatase, the enzyme which is responsible for the growth of endometrial tissue - it may constitute a targeting point in the treatment of endometriosis. So far, no adverse effects of inositol isomers have been reported. Conclusion: The use of inositol, its isomers and derivatives represents an interesting direction in the development of the treatment of many conditions associated with endocrine disorders. There is a need for further investigations and studies on larger groups of patients to exploit its potential.

Polycystic ovary syndrome (PCOS) is a symptom complex associated with increased amounts of circulating androgens in females, increased insulin resistance and obesity. The drugs, Myo-inositol, D-chiro-inositol and Metformin, which are insulin sensitizers, are very helpful in taking care of one of the key components of PCOS that is insulin resistance. Myoinositol and D-chiro-inositol are isomeric forms of inositol that have insulin-like properties, acting as second messengers in the insulin intracellular pathway; both of these molecules are involved in the increasing insulin sensitivity of different tissues to improve metabolic and ovulatory functions. This study was done to compare the effects of combination of Myo-inositol and D-chiro-inositol with the use of metformin on clinical and biochemical profile in PCOS. Methods. A prospective, randomized, comparative study was conducted on 200 patients. The patients were randomly assigned into the two groups of 100 each. Group A receiving Tab. Myoinositol 550mg twice daily and Tab. D-chiro-inositol 13.8mg twice daily and Group B receiving Tab. Metformin 500mg thrice daily. The patients were assessed by menstrual cycle regulation, hirsutism score (Ferriman Gallwey), fasting and postprandial glucose and insulin levels, serum dehydroepiandrosterone levels, serum free testosterone levels and serum luteinizing and follicle stimulating hormone ratio. Results. In both the groups there was significant improvement in all the above mentioned parameters, however the group with Combination of Myo-inositol and D-chiro-inositol had statistically significant improvement over the Metformin group. Conclusions: Combination of Myo-inositol and D-chiro-inositol and use of metformin, significantly improved insulin sensitivity in PCOS women. But combination of Myo-inositol and D-chiro-inositol was effective in controlling the hormonal profiles (luteinizing/follicle stimulating hormone ratio and free testosterone) when compared to Metformin.

he aim of this paper is to critically analyze the composition of many inositol-based products currently used to treat polycystic ovary syndrome (PCOS). Several different combinations of myo-inositol and D-chiro-inositol, with and without additional compounds such as micro- and macroelements, vitamins, and alpha-lipoic acid, have been formulated over the years. Such therapeutic proposals do not take various features of inositol stereoisomers into consideration. As an example, it is important to know that D-chiro-inositol treatment may be beneficial when administered in low doses, yet the progressive increase of its dosage results in the loss of its advantageous effects on the reproductive performance of women and a deterioration in the quality of blastocysts created via in vitro fertilization. In addition, is necessary to consider that the intestinal absorption of myo-inositol is reduced by the simultaneous administration of D-chiro-inositol since the two stereoisomers compete with each other for the same transporter that has similar affinity for each of them. A decrease in myo-inositol absorption is also found when it is coadministered with inhibitors of sugar intestinal absorption and/or types of sugars such as sorbitol, maltodextrin, and sucralose. The combination of these may require higher amounts of myo-inositol in order to reach a therapeutic dosage compared to inositol administration alone, a particularly important fact when physicians strive to obtain a specific plasma level of the stereoisomer. Finally, we must point out that D-chiro-inositol was found to be an aromatase inhibitor which increases androgens and may have harmful consequences for women. Therefore, the inositol supplements used in PCOS treatment must be carefully defined. Clinical evidence has demonstrated that the 40 :1 ratio between myo-inositol and D-chiro-inositol is the optimal combination to restore ovulation in PCOS women. Therefore, it is quite surprising to find that inositol-based treatments for PCOS seem to be randomly chosen and are often combined with useless or even counterproductive molecules, all of which can weaken myo-inositol’s efficacy. Such treatments clearly lack therapeutic rationale.

Oxidative stress is the result of overproduction of reactive oxygen species in relation to antioxidant defense levels. Physiological oxidative stress a priori exists in the women and men, but with an excess of radical compounds, it can acquire a pathological character. Oxidative stress may contribute to aging and several diseased states affecting female and male reproduction. Endothelial dysfunction secondary to oxidative stress contributes to the development of obstetric complications such as early and recurrent pregnancy loss, preeclampsia, intrauterine growth restriction, and preterm labor. Reactive oxygen and nitrogen species can negatively affect embryo implantation and may influence the development of reproductive disorders such as endometriosis and preeclampsia. Altered vasomotor functions have been demonstrated by failed embryo implantation and reduced placental perfusion in preeclampsia and endometriosis. The effects of free radicals on oocytes, sperm, and embryos have been implicated in poor reproductive outcomes in assisted reproductive techniques. The in vitro environment subjects gametes and embryos to an abundance of reactive oxygen species in the absence of enzymatic antioxidant defenses that are normally present during in vivo fertilization and pregnancy. Ideally, assisted reproductive techniques success may be attained if in vivo conditions are sufficiently imitated. To this effect, several studies have shown that antioxidants and vitamines may improve pregnancy outcomes. D-chiro-inositol (DCI) is one of such promising substances. It increases fertility due to the ovulation restoration in patients with polycystic ovaries syndrome, improves the oocytes quality, reduces oxidative and inflammatory stress, that is increases the conception probability including in assisted reproductive technologies. This gave impetus to the active inositol preparations use in the clinics of assisted reproductive technologies to obtain good quality oocytes, and reduce the hormones dose used in ovaries stimulation.