# A Comparative Analysis of Gremlin-1 (GREM1), Hyaluronic Acid Synthetase-2 (HAS2), and Prostaglandin-Endoperoxide Synthase-2 (PTGS2) Expression in Cumulus Cells Among Women with Diminished Ovarian Reserve Following Rescue In Vitro Maturation (r-IVM)

## TL;DR

This study explores how rescue in vitro maturation (r-IVM) affects gene expression and fertility outcomes in women with low ovarian reserve.

## Contribution

The study introduces a novel comparison of GREM1, PTGS2, and HAS2 gene expression in cumulus cells following r-IVM in women with diminished ovarian reserve.

## Key findings

- DOR women showed higher pregnancy and live birth rates following r-IVM, though not statistically significant.
- All studied genes were upregulated in DOR cumulus cells post-r-IVM, while NOR showed downregulation of PTGS2 and GREM1.
- r-IVM improved oocyte quality in DOR without compromising fertilization rates.

## Abstract

Managing women with diminished ovarian reserve for in vitro fertilization (IVF) is challenging, often resulting in low oocyte yield and cycle failures. We hypothesize that coupling in vitro fertilization (IVF) with rescue in vitro maturation (r-IVM) can improve overall maturation rates without compromising the overall IVF outcome. Our study compared DOR and normal ovarian reserve (NOR) cohorts by evaluating 15 immature oocyte progressions following r-IVM. We analyzed the gene expression of cumulus cells related to GREM1, PTGS2, and HAS2 to correlate with OQ, EQ, and overall IVF outcome. Significant differences were noted in AMH levels, AFCs, and oocyte numbers (p < 0.05). Following r-IVM, the DOR cohort achieved a 50% maturation rate with improved overall quality; however, the difference was not statistically significant (p > 0.05). Fertilization rates were comparable, but EQ was better in DOR. All genes in DOR were upregulated post-r-IVM, whereas NOR showed downregulation of PTGS2 and GREM1 (p < 0.05). Otherwise, DOR exhibited higher pregnancy rates and live birth rates, although the difference was not statistically significant (p > 0.05). Overall, our findings suggest that r-IVM could provide improved fertility outcomes for DOR women in standard IVF cycles.