Clinical Report: Differential Gene Expression in Granulosa Cells of Women Exhibiting Varying Ovarian Responsiveness

Overview

This study identifies 291 genes that are differentially expressed in granulosa and cumulus cells from women with varying ovarian responsiveness to controlled ovarian hyperstimulation (COH). Key findings suggest potential pathways that could be targeted to improve IVF outcomes for poor ovarian responders.

Background

Understanding the molecular response of granulosa cells to hormonal stimulation is essential for optimizing IVF treatments. Approximately 9%–24% of women undergoing IVF are classified as poor ovarian responders, leading to low oocyte retrieval and pregnancy rates. Identifying genetic markers associated with ovarian responsiveness may enhance individualized treatment strategies.

Data Highlights

Key Findings

• 291 genes are downregulated in granulosa and cumulus cells from poor ovarian responders compared to normal responders.
• Downregulated genes are enriched in pro-proliferation and DNA damage-response pathways.
• Upregulated genes in poor responders include those linked to apoptosis and ovarian malignancy.
• Six gene modules correlate significantly with the poor ovarian response phenotype.
• Core genes associated with weak ovarian responsiveness include those involved in folliculogenesis and steroidogenesis.

Clinical Implications

The identification of specific genes associated with poor ovarian response can guide clinicians in tailoring IVF protocols. Understanding these molecular mechanisms may lead to improved strategies for enhancing ovarian responsiveness and IVF success rates.

Conclusion

This research provides insights into the genetic underpinnings of ovarian responsiveness, highlighting potential targets for therapeutic intervention in IVF treatments.

Related Resources & Content

1. The Journal of Clinical Endocrinology & Metabolism, 2023 -- Differential Luteinization Characteristics of Cultured Human Granulosa Cells Derived from Small Antral and Preovulatory Follicles
2. Archives of Toxicology, 2024 -- Environmental Levels of Bisphenol Z Disrupt Mitochondrial Function and Growth Potential in Human Ovarian Granulosa Cells by Altering Metabolic Substrate Use
3. Frontiers in Endocrinology, 2026 -- The ovulation trigger method affects gonadotropin concentrations and gonadotropin receptor expression during final oocyte maturation in women
4. ESHRE guideline: ovarian stimulation for IVF/ICSI: an update in 2025 - PMC
5. Flexible progestin-primed ovarian stimulation versus a GnRH antagonist protocol in predicted suboptimal responders undergoing freeze-all cycles: a randomized non-inferiority trial - PubMed
6. Archives of Toxicology — Evaluation of Disorders Affecting Female Reproductive Health
7. Identification of genes differentially expressed in granulosa cells from women with high vs. low ovarian responsiveness
8. ESHRE guideline: ovarian stimulation for IVF/ICSI: an update in 2025 - PMC
9. Flexible progestin-primed ovarian stimulation versus a GnRH antagonist protocol in predicted suboptimal responders undergoing freeze-all cycles: a randomized non-inferiority trial - PubMed