Oxidative stress in infertility associated with endometriosis
Posted November 22, 2022
The study “The Impact of Controlled Ovarian Stimulation on Serum Oxidative Stress Markers in Infertile Women with Endometriosis Undergoing ICSI”, conducted by the INCT Hormona team of Universidade de São Paulo (USP) – Campus Ribeirão Preto – evaluated the role of oxidative stress on endometriosis-related infertility. The survey aimed to measure and to compare eight oxidative stress markers at different treatment timepoints, in addition to investigate serum levels of markers throughout stimulation, within the same group of patients. The article may be read in full at: doi: 10.3390/antiox11061161
According to the first author of the article and researcher at INCT Hormona, Dr. Michele Da Broi, the following timepoints were assessed: follicular of the cycle before ovarian stimulation (D1), 10 days after pituitary downregulation using the GnRH agonist (D2); on the day hCG administration (D3); and on the day of oocyte retrieval (D4)] of infertile women with endometriosis (regardless of disease staging -E, or subdivided into early stages -EI/II and advanced stages -EIII/IV) and infertile controls (due to tubal and/or male factors).
The specialist explains that the group has investigated the role of oxidative stress on endometriosis-related infertility for years. “Changes were found in oxidative stress markers, in the serum obtained both on the day of oocyte recovery and on the follicular phase of the cycle, as well as in the follicular fluid of infertile women with the disease, when compared to the control group, suggesting systemic and follicular impairment in these patients,” she comments. “We believe that endometriotic injuries promote a local inflammatory response, with consequent increased levels of macrophages and cytokine release, culminating in an oxidative process, which, in turn, is systematically reflected via blood circulation,” she states. “Since ovaries are vascularized, especially at final stages of follicular development/oocyte maturation, we believe that systemic oxidative stress may influence the ovarian microenvironment and compromise oocyte development in women with endometriosis,” the researcher says.
According to Dr. Da Broi, the group observed changes in oxidative stress markers in patients with endometriosis (E, EI/II, EIII/IV) at all assessed timepoints (D1, D2, D3 and D4), compared to control patients, suggesting an impact of pituitary downregulation with GnRH and ovarian stimulation on the oxidative balance of these patients, especially on the day of oocyte retrieval. “When analyzing the possible effects of the different treatment timepoints in each group individually, we observed an intense generation of reactive oxygen species in the early follicular phase, both in the control group and the endometriosis groups,” she explains.
The researcher also comments that the group was also to demonstrate that pituitary downregulation and ovarian stimulation with gonadotropins generated oxidative stress and mobilized the antioxidant system in the groups. “In patients with EI/II and EIII/IV, the mobilization of potent antioxidants was accentuated on the day of oocyte retrieval as a potential attempt to protect the oocyte from oxidative damage,” she states.
Still according to Dr. Da Broi, the fact that the group did not find differences in the ICSI outcomes among the endometriosis and control groups reinforces the hypothesis that the total antioxidant capacity was efficient in repressing oxidative damage promoted in the cycle prior to ovarian stimulation. “Under gonadotropin use, more specific antioxidants take on such protection, suggesting that antioxidant mobilization during stimulation, especially on the day that coincides with the final events of oocyte nuclear maturation, could avoid oocyte damages, even in patients with severe stages of the disease,” she comments.
In the researcher’s opinion, the results of the study suggest that pituitary downregulation with GnRH agonist and ovarian stimulation with gonadotropins may increase the generation of reactive oxygen species and exacerbate systemic oxidative stress in infertile women with endometriosis undergoing ICSI, especially on the day of oocyte retrieval. “Although we did not observe a direct impact on ICSI outcomes in these patients, possibly due to the efficient antioxidant response observed, data provide perspectives for studies, aiming to develop new therapeutic strategies using antioxidant drugs in order to improve natural fertility and/or avoiding redox oscillations observed during ovarian stimulation and thus optimize assisted reproduction outcomes in these women, who are exposed to changes in systemic and follicular oxidative status both in natural cycles and in stimulated cycles,” she concludes.