The in-vitro effect of gonadotropins’ type and combination on Granulosa cells gene expressions

Yuval Yung, Adva Aizer, Sarah Tieb, Sharon Avhar Maydan, Ettie Maman, Lilach Marom Haham, Jigal Haas, Raoul Orvieto*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: Nowadays, different modes and timing of GnRH-agonist combined with hCG trigger, for final follicular maturation, have been described. While LH + FSH are the naturally occurring final follicular maturation trigger, hCG is commonly use during stimulated cycle, and recently the introduction of the Dual/Double trigger combines LH + FSH + hCG. In the present study we aim to investigate the messenger RNA (mRNA) expression of reproduction-related genes in human granulosa cells (GCs) exposed to the aforementioned different types and combinations of gonadotropins. Material and methods: Mural GCs were obtained from follicular fluid aspirated during IVF protocol. GCs were seeded in culture for 4 days with daily medium exchange followed by administration of either hCG (1 U/ml); FSH (1 U/ml) and LH (8 U/ml); or hCG (1 U/ml) and FSH (1 U/ml) and LH (8 U/ml) for 16 h. mRNA was purified from harvested GCs and gene expression was quantitative by qPCR. Main outcome measures: The expression of genes related to steroidogenesis (StAR/ CYP19) and oocyte maturation (COX2/Amphiregulin) in cultured GCs. Results: The Dual/Double trigger (LH + FSH + hCG) showed higher activation of steroidogenesis (StAR/CYP19) and maturation (COX2/Amphiregulin) as compared to the naturally occurring trigger (LH + FSH) and the hCG triggers. Moreover, while the naturally occurring trigger (LH + FSH) activated maturation significantly and more intensely than the hCG trigger, no in between group differences were observed with regards to steroidogenic related genes. Conclusions: Our findings are in agreement with clinical experience, demonstrating the superiority of the double/dual (LH + FSH + hCG) trigger over the naturally occurring and the hCG triggers.

Original languageEnglish
Article number144
JournalReproductive Biology and Endocrinology
Issue number1
StatePublished - Dec 2022


  • Final follicular maturation
  • Gene expression
  • Gonadotropin
  • Granulosa cells
  • IVF
  • Steroidogenesis
  • Trigger


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