Clinical and Molecular Effects of GnRH Agonist and Antagonist on The Cumulus Cells in The In Vitro Fertilization Cycle

Saeid Azizollahi; Maryam Bagheri; Fedyeh Haghollahi; Seyyede Momeneh Mohammadi; Batool Hossein Rashidi

doi:10.22074/IJFS.2020.136161.1012

Clinical and Molecular Effects of GnRH Agonist and Antagonist on The Cumulus Cells in The In Vitro Fertilization Cycle

Int J Fertil Steril. 2021 Jul;15(3):202-209. doi: 10.22074/IJFS.2020.136161.1012. Epub 2021 Jun 22.

Authors

Saeid Azizollahi^{1

2}, Maryam Bagheri¹, Fedyeh Haghollahi¹, Seyyede Momeneh Mohammadi³, Batool Hossein Rashidi⁴

Affiliations

¹ Vali-e-Asr Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran.
² Cell Therapy and Regenerative Medicine Comprehensive Center, Kerman University of Medical Sciences, Kerman, Iran.
³ Department of Anatomical Sciences, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
⁴ Vali-e-Asr Reproductive Health Research Center, Tehran University of Medical Sciences, Tehran, Iran. Email: bhrashidi@tums.ac.ir.

Abstract

Background: Gonadotropin-releasing hormone (GnRH) analogues have been extensively utilized in the ovarian stimulation cycle for suppression of endogenous rapid enhancement of luteinizing hormone (LH surge). Exclusive properties and functional mechanisms of GnRH analogues in in vitro fertilization (IVF) cycles are clearly described. This study was performed to evaluate clinical and molecular impacts of the GnRH agonist and antagonist protocols in IVF cycles. For this purpose, gene expression of cumulus cells (CCs) as well as clinical and embryological parameters were evaluated and compared between two groups (GnRH agonist and antagonist) during the IVF cycle.

Materials and methods: Twenty-one infertile individuals were enrolled in this study. Subjects were randomly allocated into two groups of GnRH agonist (n=10) treated patients and GnRH antagonist (n=11) treated individuals. The defined clinical embryological parameters were compared between the two groups. Expression of BAX, BCL-2, SURVIVIN, ALCAM, and VCAN genes were assessed in the CCs of the participants using the real-time polymerase chain reaction (PCR) technique.

Results: The mean number of cumulus oocyte complex (COC), percentage of metaphase II (MII) oocytes, grade A embryo and clinical parameters did not show noticeable differences between the two groups. BAX gene expression in the CCs of the group treated with GnRH agonist was remarkably higher than those received GnRH antagonist treatment (P<0.001). The mRNA expression of BCL-2 and ALCM genes were considerably greater in the CCs of patients who underwent antagonist protocol in comparison to the group that received agonist protocol (P<0.001).

Conclusion: Despite no considerable difference in the oocyte quality, embryo development, and clinical outcomes between the group treated with GnRH agonist and the one treated with antagonist protocol, the GnRH antagonist protocol was slightly more favorable. However, further clinical studies using molecular assessments are required to elucidate this controversial subject.

Keywords: Apoptosis; Cumulus Cells; GnRH Antagonist.