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

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Abstract

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.

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Availability of data and materials

The data sets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AMH:

Anti-Müllerian hormone

BMI:

Body mass index

CAT:

Catalase

COS:

Controlled ovarian stimulation

FF:

Follicular fluid

FSH:

Follicular stimulating hormone

GCs:

Granulosa cells

Gn:

Gonadotropin hormone

GnRH:

Gonadotropin-releasing hormone

GSH-Px:

Glutathione peroxidase

hCG:

Human chorionic gonadotrophin

IVF-ET:

In vitro fertilization embryo transfer

MDA:

Malondialdehyde

OS:

Oxidative stress

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

4-HNE:

4-Hydroxynonenal

8-OHdG:

8-Hydroxy-2-deoxyguanosine

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Funding

This study was supported by the National Natural Science Foundation of China (No. 81774359, to HLD and No. 81803924, to LJF) and Postgraduate Innovation Funding Project of Hebei Province of China (No. CXZZBS2018150, to YCM).

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Author notes

  1. Yucong Ma and Zhiming Zhao contributed equally to this work.

Authors and Affiliations

  1. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China

    Yucong Ma, Yucong Cao, Jingran Geng, Lijie Fan & Huilan Du

  2. Department of Reproductive Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China

    Zhiming Zhao, Guimin Hao, Na Cui, Yanli Fan & Bulang Gao

  3. Department of Clinical Basics of Chinese Medicine, College of Integrative Medicine, Hebei Medical University, Shijiazhuang, Hebei, China

    Zhanwang Tan

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  1. Yucong Ma
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  10. Huilan Du
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Contributions

YCM, ZMZ and HLD designed this study. ZMZ and GMH collected cell samples, NC and YLF collected clinical data. YCM, YCC, ZWT, JRG and LJF detected the biochemical indicators. YCM, ZMZ and GMH analyzed the data; YCM and YCC wrote the manuscript. GBL revised the manuscript. ZMZ and HLD reviewed the manuscript. YCM and ZMZ contributed equally to this study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Huilan Du.

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The authors declared that they have no conflicts of interest.

Ethics approval

This study was approved by the Ethics Committee of Hebei University of Chinese Medicine (Shijiazhuang, China).

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All enrolled patients had informed consent and signed informed consent forms.

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Ma, Y., Zhao, Z., Hao, G. et al. Effects of multicycle gonadotropin-releasing hormone antagonist protocols on oxidative stress of follicular fluid and ovarian granulosa cells. Human Cell 34, 1324–1334 (2021). https://doi.org/10.1007/s13577-021-00545-9

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