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

Overview

Journal Int J Fertil Steril

Specialty Reproductive Medicine

Date 2021 Jun 22

PMID 34155867

Citations 1

Authors

Saeid Azizollahi

Maryam Bagheri

Fedyeh Haghollahi

Seyyede Momeneh Mohammadi

Batool Hossein Rashidi

Affiliations

Soon will be listed here.

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 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 and 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. 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 and 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.

Citing Articles

Impact of GnRH agonist and GnRH antagonist on GDF9 and BMP15 expression in mouse ovaries and oocyte development.

Guo X, Huang Y, Ou Y, Chen X, Xian Y, Chen S Anim Reprod. 2023; 20(4):e20230040.

PMID: 38074942 PMC: 10707535. DOI: 10.1590/1984-3143-AR2023-0040.

References

Chermula B, Kranc W, Jopek K, Budna-Tukan J, Hutchings G, Dompe C . Human Cumulus Cells in Long-Term In Vitro Culture Reflect Differential Expression Profile of Genes Responsible for Planned Cell Death and Aging-A Study of New Molecular Markers. Cells. 2020; 9(5). PMC: 7291080. DOI: 10.3390/cells9051265. View

Adriaenssens T, Segers I, Wathlet S, Smitz J . The cumulus cell gene expression profile of oocytes with different nuclear maturity and potential for blastocyst formation. J Assist Reprod Genet. 2010; 28(1):31-40. PMC: 3045483. DOI: 10.1007/s10815-010-9481-9. View

Lee K, Joo B, Na Y, Yoon M, Choi O, Kim W . Cumulus cells apoptosis as an indicator to predict the quality of oocytes and the outcome of IVF-ET. J Assist Reprod Genet. 2001; 18(9):490-8. PMC: 3455731. DOI: 10.1023/a:1016649026353. View

Xiao J, Su C, Zeng X . Comparisons of GnRH antagonist versus GnRH agonist protocol in supposed normal ovarian responders undergoing IVF: a systematic review and meta-analysis. PLoS One. 2014; 9(9):e106854. PMC: 4162565. DOI: 10.1371/journal.pone.0106854. View

Hussein M . Apoptosis in the ovary: molecular mechanisms. Hum Reprod Update. 2005; 11(2):162-77. DOI: 10.1093/humupd/dmi001. View

Assou S, Haouzi D, Mahmoud K, Aouacheria A, Guillemin Y, Pantesco V . A non-invasive test for assessing embryo potential by gene expression profiles of human cumulus cells: a proof of concept study. Mol Hum Reprod. 2008; 14(12):711-9. DOI: 10.1093/molehr/gan067. View

Geng Y, Xun Y, Hu S, Lai Q, Jin L . GnRH antagonist versus follicular-phase single-dose GnRH agonist protocol in patients of normal ovarian responses during controlled ovarian stimulation. Gynecol Endocrinol. 2018; 35(4):309-313. DOI: 10.1080/09513590.2018.1528221. View

Clavero A, Castilla J, Nunez A, Garcia-Pena M, Maldonado V, Fontes J . Apoptosis in human granulosa cells after induction of ovulation in women participating in an intracytoplasmic sperm injection program. Eur J Obstet Gynecol Reprod Biol. 2003; 110(2):181-5. DOI: 10.1016/s0301-2115(03)00243-4. View

Lee S, Oh H, Kim M, Lee B . Exosomes derived from oviduct cells mediate the EGFR/MAPK signaling pathway in cumulus cells. J Cell Physiol. 2019; 235(2):1386-1404. DOI: 10.1002/jcp.29058. View

10.

Tabibnejad N, Sheikhha M, Ghasemi N, Fesahat F, Soleimani M, Aflatoonian A . Association between early embryo morphokinetics plus cumulus cell gene expression and assisted reproduction outcomes in polycystic ovary syndrome women. Reprod Biomed Online. 2018; 38(2):139-151. DOI: 10.1016/j.rbmo.2018.10.010. View

11.

Prapas Y, Petousis S, Dagklis T, Panagiotidis Y, Papatheodorou A, Assunta I . GnRH antagonist versus long GnRH agonist protocol in poor IVF responders: a randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2012; 166(1):43-6. DOI: 10.1016/j.ejogrb.2012.09.008. View

12.

Wu H, Chang H, Leung P . Gonadotropin-releasing hormone analogs: Mechanisms of action and clinical applications in female reproduction. Front Neuroendocrinol. 2020; 60:100876. DOI: 10.1016/j.yfrne.2020.100876. View

13.

Johnson A, Langer J, Bridgham J . Survivin as a cell cycle-related and antiapoptotic protein in granulosa cells. Endocrinology. 2002; 143(9):3405-13. DOI: 10.1210/en.2002-220107. View

14.

van Montfoort A, Dumoulin J, Kester A, Evers J . Early cleavage is a valuable addition to existing embryo selection parameters: a study using single embryo transfers. Hum Reprod. 2004; 19(9):2103-8. DOI: 10.1093/humrep/deh385. View

15.

Chen Q, Yu F, Li Y, Zhang A, Zhu X . Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium. Drug Des Devel Ther. 2019; 13:1855-1863. PMC: 6554521. DOI: 10.2147/DDDT.S201871. View

16.

Takahashi K, Mukaida T, Tomiyama T, Goto T, Oka C . GnRH antagonist improved blastocyst quality and pregnancy outcome after multiple failures of IVF/ICSI-ET with a GnRH agonist protocol. J Assist Reprod Genet. 2004; 21(9):317-22. PMC: 3468267. DOI: 10.1023/b:jarg.0000045470.68525.a4. View

17.

Adriaenssens T, Van Vaerenbergh I, Coucke W, Segers I, Verheyen G, Anckaert E . Cumulus-corona gene expression analysis combined with morphological embryo scoring in single embryo transfer cycles increases live birth after fresh transfer and decreases time to pregnancy. J Assist Reprod Genet. 2019; 36(3):433-443. PMC: 6439096. DOI: 10.1007/s10815-018-01398-2. View

18.

Lin M, Wu F, Hwu Y, Lee R, Li R, Li S . Dual trigger with gonadotropin releasing hormone agonist and human chorionic gonadotropin significantly improves live birth rate for women with diminished ovarian reserve. Reprod Biol Endocrinol. 2019; 17(1):7. PMC: 6320621. DOI: 10.1186/s12958-018-0451-x. View

19.

Kara M, Aydin T, Aran T, Turktekin N, Ozdemir B . Comparison of GnRH agonist and antagonist protocols in normoresponder patients who had IVF-ICSI. Arch Gynecol Obstet. 2013; 288(6):1413-6. DOI: 10.1007/s00404-013-2903-z. View

20.

Chi X, Zhang T, Chu X, Zhen J, Zhang D . The regulatory effect of Genistein on granulosa cell in ovary of rat with PCOS through Bcl-2 and Bax signaling pathways. J Vet Med Sci. 2018; 80(8):1348-1355. PMC: 6115251. DOI: 10.1292/jvms.17-0001. View