The role of Inositol in pregnancy

Many patients consider inositol a necessary medication in IVF treatment regardless of what actually causes them having trouble getting pregnant. We should figure out the effects of the supplements before taking them.
Consultation
2022-11-25
Author: Dr. I-Ting Liang, MD

Inositol, also known as vitamin B8, isn’t really a vitamin, considering its structure. It’s actually a polyol, a derivative of glucose.There are currently nine isomers of inositol, and the most representative of which is myoinositol and d-chiro inositol.

D-chiro inositol is produced from the conversion of myoinositol. These two inositols are converted in different proportions in various cells according to the needs. Since inositol-derived phosphoinositide is the second messenger in the cellular signal transduction chain, it also regulates intracellular calcium channels and participates in many cellular functions.

In oocytes, the former is involved in the action of growth hormone and insulin receptors. The latter is involved in the action of follicle-stimulating hormone and luteinizing hormone and exerts a synergistic effect. In addition, the final maturation and fertilization of oocytes require the participation of phosphoinositide, so it is widely used in the field of reproductive endocrinology.

The following three aspects are discussed:

Inositol and polycystic ovaries

The main mechanism of polycystic ovaries is chronic anovulation and insulin resistance, which leads to the increase of insulin, which increases the male hormone produced by follicles, further strengthens insulin resistance and chronic anovulation, forming a vicious circle. Therefore, in the treatment of polycystic ovaries, most of the goals are to break this vicious circle.

Inositol and d-chiro inositol have their own roles in follicles. The former strengthens the effect of follicle-stimulating hormone, while the latter enhances the production of male hormones caused by insulin. Together, they promote the use and metabolism of insulin. The ovaries rely on a balance of these two inositols to regulate its hormone production and follicle growth.

Previous studies showed that in the follicular fluid of polycystic ovaries, excessive insulin leads to the excessive conversion of inositol to d-chiro inositol, which increases the production of male hormones, which in turn hinders the growth of follicles. Inositol supplementation can increase the metabolism of insulin, breaking this vicious cycle. In addition, myo-inositol increases the effect of follicle-stimulating hormones, reduces the accumulation of male hormones, and makes it easier for follicles to grow.

However, a systematic review in 2017 showed that inositol supplementation did reduce insulin resistance and blood insulin concentration, but the regulation of androgen hormones only showed a downward trend. Some effects of inositol currently shown in IVF treatment with polycystic ovary conditions include reduced doses and days of stimulation of follicle-stimulating hormone, reduced cases of ovarian hyperstimulation, a higher proportion of good oocytes and embryos, increased pregnancy rate and reduced miscarriage rate. There’s still some controversy regarding the part about good oocytes/embryos and pregnancy rate though.

In current studies, it is considered the most beneficial for metabolic improvement if the supplementation of myo-inositol and d-chiro inositol is in the ratio of 40:1. As for applying to IVF, more evidence is needed due to the huge differences in the dosage, proportion, time, etc. used in each study. Most studies use inositol 2~4g per day, from one month to three months. However, it should be noted that polycystic ovary cases in Asia are not always combined with insulin resistance. Whether they are suitable for supplementation should be discussed with a doctor.

Inositol and non-polycystic ovary IVF groups

Currently, only a few studies have completely excluded the polycystic ovary population. The most representative one is a 2012 study, comparing the use of folic acid 400 μg/day and folic acid 400 μg/day plus inositol 4g/day three months before ovarian stimulation. The latter group used fewer doses of follicle stimulating hormone, but the number of oocytes retrieved also decreased, thus fewer embryos. This study gave no good explanation for this phenomenon, but I think it is related to the enhanced effect of follicle-stimulating hormone by inositol, which reduces the stimulation intensity of follicle-stimulating hormone after the performance of estrogen is better.

Inositol and poor ovarian response groups in IVF 

A 2015 study also compared the effects between the use of folic acid and the use of folic acid plus inositol 3 months prior to treatment. The results showed the latter group used a lower dose of follicle-stimulating hormone. Although there was no significant difference in the number of oocytes retrieved, the latter group had a higher ratio of mature oocytes.

Discussion with your doctor  is needed before treatment. This article only reflects the current treatment situation and suggestions.

*This article only reflects the treatment status at the time of writing, and the actual situation should be discussed with the doctor.