The impact of Oxidative Stress factors on female fertility

Oxidative stress is implicated in the deterioration of human health and quality of life as part of the pathophysiological mechanisms leading to cancer and inflammation. Its impact on reproductive function is a subject of scientific research aimed at mitigating its adverse effects on male and female fertility. The aim of this doctoral thesis is to study the effect of oxidative stress factors (age, body mass index, smoking, alcohol consumption) in a population of infertile women who underwent in vitro fertilization (IVF) in the region of Thrace. It also explores the variations these factors may present among different social and cultural groups in the region and their impact on IVF outcome parameters. Additionally, we investigate the role of the soluble receptor for advanced glycation end products (sRAGEs) as a potential biomarker of oxidative stress in the follicular fluid of infertile women with polycystic ovary syndrome (PCOS) and endometriosis. Materials and methods: The study population consisted of 610 women from the Thrace region who underwent IVF at the IVF Laboratory of the University General Hospital of Alexandroupolis between 2012 and 2018. Anthropometric and demographic parameters related to oxidative stress were recorded and statistically analyzed, and their correlation with ovarian stimulation response indicators (number of follicles, mature oocytes, embryos available for embryo transfer, total number of gonadotropin units used) was assessed. Furthermore, the correlation of soluble receptor for advanced glycation end products (sRAGE) as an oxidative stress assessment marker in the follicular fluid of infertile women with PCOS and endometriosis was examined in relation to epidemiological oxidative stress parameters, hormonal parameters, and ovarian stimulation response indicators. Results: Among the study population, increased mean BMI and higher rates of smoking and alcohol consumption were observed. In the female infertility category, multivariate analysis showed that age and smoking were independent predective factors for ovarian stimulation response. In the subgroup of women with an unknown etiology of infertility, a statistically significant negative correlation was found between the number of follicles and the women's age. In the female infertility subgroup, Christian women undergoing IVF were older, had a lower BMI, and consumed more alcohol, while their smoking habits were similar to those of Muslim women. Women with PCOS had higher levels of follicular fluid (ff) sRAGE compared to the control group. In this group, ff sRAGE levels did not show a significant correlation with the number of retrieved oocytes, the number of MII oocytes, the number of embryos, or the MII oocytes-to-total retrieved oocytes ratio. In the non-PCOS group, ff sRAGE levels were negatively correlated with oocyte quality, as expressed by the MII-to-total oocytes ratio. In women with endometriosis, a negative but non-significant correlation was observed between BMI and ff sRAGE levels, while no statistically significant correlation was found between ff sRAGE levels and smoking or alcohol consumption. In the same group, a positive correlation was observed between ff sRAGE levels and serum and follicular fluid AMH, total number of follicles >15 mm, number of retrieved oocytes, number of MII oocytes, and number of embryos available for transfer. Conclusions: This study highlights the particular characteristics of infertile women in the Thrace region regarding oxidative stress parameters affecting their reproductive function. The role of ff sRAGE levels as an oxidative stress assessment marker in infertile women requires further investigation and understanding to develop future therapeutic strategies aimed at improving their fertility.