Altered redox state in the endometrium of patients undergoing ovarian stimulation for assisted reproduction technology

OBJECTIVE: Oxidative stress is the result of alteration in the cellular balance between oxidant and antioxidants. Oxidative stress has been linked to infertility associated diseases such as postoperative adhesions, fibroids, endometriosis, and polycystic ovary syndrome (PCOS). The sources and nature of oxidative stress associated with assisted reproductive technology (ART) are not yet known. We have previously shown that ovarian stimulation is associated with an increase in superoxide dismutase, a potent antioxidant, as well as myeloperoxidase, a potent oxidant and inflammatory marker. In this study, we sought to determine the effects of ovarian stimulation for ART on the expression of additional antioxidants, glutathione reductase (GSR) and glutathione peroxidase (GPX1), and oxidants, nitric oxide synthase (NOS) isoforms (inducible (iNOS), neuronal (nNOS) and endothelial (eNOS), in endometrial tissues during the peri-implantation period. DESIGN: Prospective controlled study. MATERIALS AND METHODS: Endometrial tissue samples were collected with a flexible pipelle from women (n=9) during a natural cycle (control) and oocyte donors (n=9, treated) during an assisted reproductive technology (ART) cycle at hypothetical day 3 of embryo transfer (LH+5 or hCG+5). RNA was extracted, and subjected to quantitative real-time RTPCR for NOS isoforms, GSR and GPX1. RESULTS: There was a 2.2 fold increase in GPX1 and no change in GSR mRNA levels in stimulated as compared to control endometrium. There was a 1.2, 2.1, and 4.7 fold increase in eNOS, nNOS, and iNOS mRNA levels, respectively, in stimulated as compared to control endometrium. CONCLUSION: Ovarian stimulation significantly alters oxidative stress profile favoring an endometrial pro-oxidant state, which may impact the overall success of implantation. This provides the base to future clinical trials testing the effects of antioxidant supplements during stimulation.