Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improvingin vitrofertilization of patients with polycystic ovarian syndrome

Abstract

Polycystic ovarian syndrome (PCOS) induces anovulation in women of reproductive age, and is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Indeed, PCOS women are characterized by poor quality oocytes. Therefore, a treatment for enhancing oocyte quality becomes crucial for these patients. Myo-Inositol and melatonin proved to be efficient predictors for positive IVF outcomes, correlating with high oocyte quality. We tested the synergistic effect of myo-inositol and melatonin in IVF protocols with PCOS patients in a randomized, controlled, double-blind trial. Five-hundred twenty-six PCOS women were divided into three groups: Controls (only folic acid: 400 mcg), Group A (Inofolic® plus, a daily dose of myo-inositol: 4000 mg, folic acid: 400 mcg, and melatonin: 3 mg), and Group B (Inofolic®, a daily dose of myo-inositol: 4000 mg, and folic acid: 400 mcg). The main outcome measures were oocyte and embryo quality, clinical pregnancy and implantation rates. The treatment lasted from the first day of the cycle until 14 days after embryo transfer. Myo-inositol and melatonin have shown to enhance, synergistically, oocyte and embryo quality. In consideration of the beneficial effect observed in our trial and on the bases of previous studies, we decided to integrate routinely MI and M supplementation in the IVF protocols. The same treatment should be taken carefully in consideration in all procedures of this kind.

Inositol and In Vitro Fertilization with Embryo Transfer

“…A recent analysis of follicular fluid in PCOS patients shows a 500-fold reduction in the amount of MYO, associated with an increase of insulin resistance, hyperinsulinemia, and luteinizing hormone levels [30]. …”

“…Patients take inositols from the first day of the cycle until 14 days after embryo transfer. They observed that myoinositol and melatonin enhance, synergistically, oocyte and embryo quality so these two can be integrated routinely in association with drugs for ovarian stimulation during IVF cycle [30]. …”

Pleiotropic roles of melatonin in endometriosis, recurrent spontaneous abortion, and polycystic ovary syndrome

“…28 The oral supplementation of melatonin raises its concentration in the follicular fluid, 130 which defines a follicle containing high-quality oocytes. Similarly, stimulated macrophages and neutrophils were also found to deteriorate oocyte quality independent of cumulus cells presence in a time-dependent fashion, which could be also prevented by melatonin.…”

Sleep, Circadian Rhythms, and Fertility

“…Melatonin supplementation (3 mg with duration of treatment lasting from 2 weeks to 3 months) has resulted in improvement of IVF outcomes including number of oocytes retrieved [36], oocyte maturation and quality [36,91,121], fertilization rate [82,113,121], and embryo quality [36,82,91,121]. Improvements in IVF outcomes with melatonin supplementation have also been noted specifically in women with polycystic ovary syndrome (PCOS) [83]. Because of these promising early findings, a double-blind randomized placebo-controlled dose-response trial has been devised [39].…”