What is the Impact of Ovulation Trigger Regimen on Cumulus Cells’ Transcriptome among High and Normal Responder Patients? An Extensive Investigation by Next Generation Sequencing

Introduction: Triggering regimen poses crucial impact on oocyte maturation during In Vitro Fertilization (IVF). Cumulus cells (CCs) are in close contact with the oocytes and their transcriptome may improve our understanding of final oocyte maturation.

Aim: To investigate the impact of ovulation trigger on CCs transcriptome among patients with high and normal ovarian reserve (HR and NR, respectively).

Materials & Methods: This prospective study included six HR and six NR patients undergoing IVF with antagonist protocol. Each cohort was divided to two matched groups (three patients each) according to ovulation trigger: single trigger (ST) of GnRH agonist (GnRHa, Lupron 0.2cc) versus double trigger (DT) of 1000 IU HCG+GnRHa among HR; ST of 5000 IU HCG vs. DT of 5000 IU HCG+GnRHa in NR. CCs were pooled from 3 MII oocytes in each patient and their transcriptome was evaluated by next generation sequencing. Sequences were aligned to hg19 followed by differential expression and filtered by false discovery rate (FDR<0.05) and fold change (FC2).

Results: Average mapping rate was 94.2% and 93.8% for the HR and NR, respectively. 123 and 21 genes were differentially expressed (DE), respectively, between trigger regimens. 43 and 7 genes, respectively, are directly involved in ovarian processes such as follicular maturation, ovulation, endocrine function and luteinization. These genes are involved in defined cellular pathways such as cell-cycle regulation (ex. MAPK and TGFb), steroid metabolism and extracellular matrix remodeling.

Conclusions: Triggering protocol alters CCs transcriptome. DE genes, mostly detected among HR patients, are involved in central ovarian processes and pathways which impact follicular development oocyte maturation.