Abstract
Background: Repeated controlled ovarian stimulation (COS) has adverse effects on clinical pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET) patients. The effect of repeated antagonist protocols on oxidative stress (OS) in follicular fluid (FF) and ovarian granulosa cells (GC) remains unclear. Objective: To study the effects of repeated multicycle gonadotropin-releasing hormone antagonist (GnRH-ant) protocols on OS markers of FF and ovarian GC. Methods: A total of 145 patients were enrolled and divided into four groups: 1 cycle group (n = 42), 2 cycles group (n = 37), 3 cycles group (n = 45), and 4-5 cycles group (n = 21). The FF and ovarian GC of the patients were collected on the day of last egg retrieval. Levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in FF and ovarian GC were analyzed. Results: With the increase of GnRH-ant protocol cycles, the serum estradiol levels on human chorionic gonadotrophin (hCG) injection day, number of retrieved oocytes, 2PN embryos, and the rates of high-quality embryos, implantation and clinical pregnancy were all significantly decreased, while the gonadotropin (Gn) usage showed an increasing trend. Compared with 1 or 2 cycles, the 8-OHdG and SOD were significantly increased in the 3 to 5 cycles, while the CAT and GSH-Px levels were significantly decreased. Conclusion: Repeated COS with the use of GnRH-ant protocols results in OS and changes the follicle microenvironment of FF and GC, possibly leading to poor IVF outcomes in patients with 3-5 cycles of COS.
Effects of multicycle gonadotropin-releasing hormone antagonist protocols on oxidative stress of follicular fluid and ovarian granulosa cells
