Myo-inositol improves quality of oocyte, embryo in ART-treated women with PCOS
Women with polycystic ovarian syndrome (PCOS) undergoing assisted reproductive technology (ART) cycles may benefit from the administration of myo-inositol (MI) which improves oocyte and embryo quality due to alterations in gene expression in granulosa cells, according to a study presented at ESHRE 2019.
“Despite the higher number of oocytes retrieved from PCOS patients during IVF*, the quality and maturity of oocytes and embryo are lower than [that of] non-PCOS infertile women … [thus leading to] repeated ART attempts,” explained the researchers. “[Our findings showed that] MI supplementation in ART cycles among patients with PCOS increases the percentage of metaphase II oocytes to total oocytes, as well as the fertilization rate and the ratio of good quality embryos.”
Fifty IVF candidates aged 20–35 years were randomized 1:1 to receive daily doses of 400 mg folic acid either alone (placebo) or in combination with MI 4 g from a month prior to the IVF cycle until the day of ovum pick-up. [ESHRE 2019, abstract P-690; Arch Gynecol Obstet 2019;299:1701-1707]
Despite the lack of significant between-group difference in the number of retrieved oocytes (p<0.6), there was a significant increase in the percentage of metaphase II oocytes (78.7 percent vs 58.3 percent; p=0.003) and fertilization rate (65.2 percent vs 46.8 percent; p=0.03) with MI vs placebo.
“[MI is] considered as an insulin sensitizer and its role in improving the metabolic status of patients with PCOS might be the reason for improving the quality of oocyte,” said the researchers.
MI also improved the percentage of grade 1 embryos (p=0.006) and reduced the fraction of grade 3 (bad) embryos (p=0.029). However, this requires further elucidation considering the contradicting results in other studies, [Eur Rev Med Pharmacol Sci 2011;15:509-514; Gynecol Endocrinol 2016;32:69-73] which could be attributed to differences in the type of ovarian stimulation protocols or the duration of the intervention used, noted the researchers.
Gene expression of PGK1**, RGS2***, and CDC42#, which influence oocyte quality in granulosa cells, was significantly higher with MI vs placebo (p=0.013, p=0.021, and p<0.001, respectively).
PGK1 plays an important role in glycolysis, which is crucial for oocyte maturation and competence. [Fertil Steril 2013;99:979-997; Cell Mol Life Sci 2015;72:251-271] “In the final stages of folliculogenesis, oocytes are unable to oxidize glucose during glycolysis … and are highly dependent on glycolytic products provided by granulosa cells for energy supplementation,” noted the researchers. Therefore, increasing PGK1 expression can improve glycogenesis in the granulosa cells, consequently influencing oocyte maturation and competence, they added.
Ovarian stimulation may induce premature Ca2+ release before fertilization of the metaphase II oocyte, thus causing parthenogenesis and inhibiting fertilization. [Development 2015;142:2633-2640; Mol Hum Reprod 2010;16:87-96] “One of the most important proteins that prevent Ca2+ increase is RGS2. Therefore, [the increased] fertilization rate following MI treatment can be due to increased expression of [RGS2],” said the researchers.
Overexpression of CDC42 can increase cell division and decrease apoptosis in granulosa cells, which can lead to improved quality of follicles and oocytes, noted the researchers. [J Biol Chem 2001;276:19656-19663]
However, despite its molecular effect, MI did not improve cumulative pregnancy rate (40 percent vs 35 percent; p=0.74). The researchers attributed this to the small study sample and called for larger trials to further elucidate the findings. “If the clinical efficacy of our findings on pregnancy rate is approved by further [randomized controlled trials], the use of MI as an adjuvant in ART cycles can be suggested for PCOS patients.”