BIOKART: Inflammation and oxidative stress mediators as predictors of oocyte quality and pregnancy outcomes in assisted reproduction: from biochemistry to clinic

Summary:

About 10-15% of the overall population in reproductive age is infertile. The European Action Plan for Sexual and Reproductive Health is intended to accelerate progress towards improving sexual and reproductive health in line with the European health and well-being policy framework. Although infertility is a critical component of reproductive health, it has often been neglected in these efforts.

There are increasing evidences that oocyte quality affects fertilization and subsequent pregnancy establishment. Serum estradiol levels and follicle size are routine parameters used to monitor follicular development and oocyte maturation, whereas morphological evaluation is the most frequent analysis of oocyte quality. Although simple and quick, these methods are poor predictors of oocyte quality and considered unsatisfactory.

Follicular fluid forms the biochemical micro-environment of the oocyte before ovulation and assists in estimating the developmental competence of female gametes. It is chemically rich in regulators of oxidative stress and antioxidant products and, thus, low intrafollicular stress mediators are commonly regarded as promising markers for predicting of fertilization success. On the other hand, inflammation is an intricate network of chemical signals and cell types that can disturb oocyte maturation and folliculogenesis, thereby influencing oocyte quality. The inflammatory process is the result of the balance between pro- and anti-inflammatory molecules and it is now well established that ovulation involve a shift from a cytokine-regulated inflammatory process into an anti-inflammatory milieu.

It is a priority to find new factors that help optimize the entire process and various studies have looked for specific molecular markers of oocyte quality by mainly focusing on the components of follicular fluid and on oocyte gene expression analysis. However, none of the known molecules appear to be reliable predictors of oocyte quality. Endometriosis, obesity and polycystic ovarian syndrome are all conditions associated with unbalanced redox state and inflammation control and also with female infertility/subfertility. Thus, we intend to study the interrelation among inflammation and oxidative stress in these conditions. This project also aims to determine how aberrant inflammation and/or oxidative stress can alter normal ovarian follicular dynamics resulting in impaired oocyte quality, and associated infertility. Finally, we aim to identify predictive markers for oocyte maturation, fertilization, embryo quality, and pregnancy rates. Once fully validated, these new approaches are expected to improve oocyte and embryo selection, leading to improved implantation rates and greater chances of success using elective single embryo transfer.