Myo-Inositol and Its Derivatives: Their Roles in the Challenges of Infertility

Abstract

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositol may influence oocyte maturation and improve intracellular Ca²⁺ oscillation in the oocytes, and it has been proposed as a potential intervention for restoring spontaneous ovulation. The MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase, thus regulating androgen synthesis. Under physiological conditions, the MYO/DCI ratio is maintained at 40:1 in plasma. In women with PCOS, the MYO/DCI ratio is lowered to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling, inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositol may be a promising strategy to address female infertility and sustain a healthy pregnancy.

Keywords: D-chiro-inositol; PCOS; fertility; gestational diabetes mellitus; in vitro fertilization; myo-inositol; oocytes.

Figure 1

Structures of the nine isomers of inositol.

Figure 2

The ovarian paradox. In physiological conditions, when insulin binds to its receptor, inositol phosphoglycans, are hydrolyzed from the cytoplasmic membrane, releasing MYO, which then promotes glucose uptake via the Glut-4 receptor. The enzyme epimerase simultaneously catalyzes the conversion of MYO to DCI, facilitating glycogen synthesis. In cases of insulin resistance, intracellular insulin signaling is down-regulated, leading to a systemic shortage of DCI. By contrast, ovaries retain normal insulin sensitivity, which is a phenomenon referred to as the “ovarian paradox”. Therefore, in the ovaries, hyperglycemic conditions induce an overstimulation of the insulin receptor, which enhances the conversion of MYO to DCI, resulting in an abnormal increase in DCI levels.

Figure 3

Classic Rotterdam criteria. A Venn diagram showing the relationship between the four Rotterdam phenotypes. Abbreviations: PCOM, polycystic ovarian morphology.