Introduction
endocrine disorder, PCOS, infertility, metabolic derangements
POLYCYSTIC OVARY SYNDROME, OVARIAN HYPERSTIMULATION, DEGENERATION, ENDOCRINE DISORDER
Homocysteine (Hcy) is a non-proteogenic amino acid resulting from (adenosyl)methionine de-methylation in transmethylation reactions. Due to the wide involvement of carbon unit trafficking in animal metabolism, Hcy is massively and continuously produced within cells with one-fifth to one-sixth of the total Hcy pool renovated every hour [The OCM is fundamental for gametogenesis and embryogenesis. Methylations are necessary to ensure DNA methylation as part of the epigenetic programming as well as for key molecular syntheses and in general for tissue growth and differentiation. The endogenous antioxidant system supported by GSH is in turn necessary to neutralize the reactive oxygen species (ROS) generated in mitochondria, thus protecting the gametes and embryo DNA from oxidative degeneration. Accordingly, HHcy has been linked to defective gametogenesis in both sexes and to couple infertility [Polycystic ovary syndrome (PCOS) is an endocrine disorder occurring in up to 20% of women in reproductive age [HHcy has been shown to mark a worst reproductive prognosis in PCOS women undergoing intra-uterine insemination (IUI). In a IUI trial [Berker et al. (2009) found that a higher amount of Hcy in follicular fluid of PCOS women undergoing oocyte pick-up following FSH stimulation sharply marked lower oocyte quality, fertilization rates, embryo quality, and pregnancy rates with no pregnancies occurring in women whose sampled follicles contained more than 8 μmolar Hcy [Excess of Hcy is removed by three alternative pathways (Fig. Pathways for homocysteine removal. Any excess of Hcy is toxic and must be eliminated. On the other side, homocysteine is the substrate for other syntheses and a balanced partitioning among the available pathways is essential to avoid metabolic derangements. Hcy can be re-methylated to methionine/SAMe using the methyl group from 5MTHF/CH3B12 (①) under the sequential actions of MTRR and MS. In alternative, it can be re-methylated by BHMT using the methyl group from betaine (②), which happens mainly in the liver. Finally, Hcy can be transsulfurated to cysteine by the sequential action of CBS and CSE (③). The latter enzymes exert an ambiguous recognition of their substrates and may work in a reverse manner (alternative transsulfurations) using cysteine and Hcy to release the reducing gasotransmitter Hydrogen sulfide (HThe present study was intended to preliminarily explore the role of follicular Hcy in predicting the reproductive potential of oocytes, i.e., their ability to generate a viable blastocyst, in assisted reproduction cycles and the ability of a micronutrient support to decrease Hcy concentration in the follicular fluid of PCOS women undergoing controlled ovarian hyperstimulation (COH) for assisted reproduction purposes.