Effects of multicycle gonadotropin-releasing hormone antagonist protocols on oxidative stress of follicular fluid and ovarian granulosa cells

• Published in: Human cell : official journal of Human Cell Research Society Vol. 34; no. 5; pp. 1324 - 1334
• Main Authors: Ma, Yucong, Zhao, Zhiming, Hao, Guimin, Cui, Na, Fan, Yanli, Cao, Yucong, Tan, Zhanwang, Geng, Jingran, Fan, Lijie, Du, Huilan, Gao, Bulang
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-09-2021; Springer Nature B.V
• Subjects: 17β-Estradiol; Adult; Biomedical and Life Sciences; Catalase; Catalase - metabolism; Cell Biology; Deoxyguanosine; Embryos; Female; Follicular fluid; Follicular Fluid - metabolism; Glutathione peroxidase; Glutathione Peroxidase - metabolism; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Gonadotropins; Granulosa cells; Granulosa Cells - metabolism; Gynecology; Humans; Implantation; Life Sciences; Malondialdehyde; Microenvironments; Oncology; Oocytes; Ovaries; Ovulation Induction - methods; Oxidative stress; Oxidative Stress - drug effects; Patients; Pituitary (anterior); Reproductive Medicine; Research Article; Stem Cells; Superoxide dismutase; Surgery; Granulosa cells; Oxidative stress; Follicular fluid; Repeated controlled ovarian stimulation; Gonadotropin-releasing hormone antagonist protocol
• ISSN: 1749-0774; 0914-7470; 1749-0774
• DOI: 10.1007/s13577-021-00545-9

The effect of repeated multicycle gonadotropin-releasing hormone antagonist (GnRH-ant) protocols on oxidative stress (OS) in follicular fluid (FF) and ovarian granulosa cells (GCs) remains unclear. This study investigated the effects of repeated multicycle GnRH-ant protocols on OS markers of FF and ovarian GCs. 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 GCs of the patients were collected on the day of last oocyte retrieval and the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were tested by ELISA. The results showed that the serum estradiol levels on hCG injection day in the 3 and 4–5 cycles were significantly (
P
 < 0.05) lower than in the 1 and 2 cycles. The number of retrieved oocytes (12.1 ± 3.3 in cycle 1, 11.7 ± 3.1 in cycle 2, 10.4 ± 2.4 in cycle 3, and 9.4 ± 2.4 in cycles 4–5), embryos with two pronuclei (7.6 ± 3.0 in cycle 1, 7.0 ± 2.5 in cycle 2, 6.2 ± 2.6 in cycle 3, and 5.5 ± 2.1 in cycles 4–5), and the rates of high-quality embryos (52.2% in cycle 1, 47.9% in cycle 2, 38.6% in cycle 3, and 36.5% in cycles 4–5), implantation (35.4% in cycle 1, 32.4% in cycle 2, 23.8% in cycle 3, and 22.9% in cycles 4–5) and clinical pregnancy (50.0% in cycle 1, 43.2% in cycle 2, 33.3% in cycle 3, and 23.8% in cycles 4–5) in cycles 3 and 4–5 were significantly (
P
 < 0.05) lower than those in cycles 1 and 2. Compared with 1 and 2 cycles, the 8-OHdG and SOD were significantly increased in the 3–5 cycles, while the CAT and GSH-Px levels were significantly decreased. Together, this study reveals repeated COS with the use of GnRH-ant protocols results in OS and changes the follicle microenvironment of FF and GCs, possibly leading to poor IVF outcomes in patients with 3–5 cycles of COS.