ArticleReproductive biology and endocrinology : RB&E2024
Melatonin supplementation attenuates cuproptosis and ferroptosis in aging cumulus and granulosa cells: potential for improving IVF outcomes in advanced maternal age.
Article in Reproductive biology and endocrinology : RB&E, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The effects of oral antioxidants on outcomes of assisted reproductive technology: a systematic review and meta-analysis of randomized controlled trials.Frontiers in endocrinology · 2026Pooled it
- The Molecular and Cellular Mechanisms of Melatonin: From Physiological Actions to Clinical Applications in Reproductive Medicine.International journal of molecular sciences · 2026Review
- Melatonin in ovarian function and dysfunction: Molecular mechanisms and therapeutic potential.Journal of ovarian research · 2026Review
- The crosslink between autophagy and ferroptosis in polycystic ovary syndrome: from synergistic pathogenesis to targeted therapy.Journal of ovarian research · 2026Review
- SOD1 deficiency drives ferroptosis-linked oxidative and reproductive aging, mitigated by ginseng root extract.GeroScience · 2026Article
- Review
- Melatonin as a Guardian of Mitochondria: Mechanisms and Therapeutic Potential in Neurodegenerative Diseases.Biology · 2026Review
- From gut-reproductive microbiota to ferroptosis: a comprehensive insight into the molecular-pathogenicity of endometriosis.Frontiers in immunology · 2026Review
- Preventing ovarian aging: from redox-targeted strategies to extracellular vesicle-based therapies.Frontiers in aging · 2026Review
- Unveiling the metal-driven death: ferroptosis and cuproptosis in leukemia.European journal of medical research · 2025Review
- Investigating the effects of melatonin on structural and vascular changes in an experimentally induced ovarian hyperstimulation syndrome model : Effects of melatonin on experimentally induced ovarian hyperstimulation syndrome.Histochemistry and cell biology · 2025Article
- Review
- Unraveling mitochondrial dysfunction in polycystic ovary syndrome: Pathophysiological insights.Journal of the Chinese Medical Association : JCMA · 2025Review
- Ferroptosis in the Ovarian Follicular Microenvironment: A Redox-Dependent Cell Death Pathway with Emerging Roles in PCOS, Oocyte Quality, and IVF Outcomes.International journal of molecular sciences · 2025Review
- The Impact of Melatonin Supplementation on Various Aspects of Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.Health science reports · 2025Review
- Mitochondrial dysfunction in oocytes: implications for fertility and ageing.Journal of ovarian research · 2025Review
- Melatonin Interplay in Physiology and Disease-The Fountain of Eternal Youth Revisited.Biomolecules · 2025Review
- Ovarian Endometrioma Disrupts Oocyte-Cumulus Communication and Mitochondrial Function, With Melatonin Mitigating the Effects.Cell proliferation · 2025Article
- Oocyte and dietary supplements: a mini review.Frontiers in cell and developmental biology · 2025Review
- The emerging role of cuproptosis in spinal cord injury.Frontiers in immunology · 2025Review
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3 authors.
Funding
Abstract
backgroundAdvanced maternal age is associated with decreased oocyte quantity and quality and in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes in women of advanced maternal age by modulating cuproptosis and ferroptosis.
methodsThis prospective cohort study included 161 women aged 35-45 years undergoing IVF-frozen embryo transfer cycles. Participants were assigned to either melatonin (n = 86, 2 mg daily for ≥ 8 weeks) or control (n = 75) groups. Cumulus cells were analyzed for cuproptosis and ferroptosis-related gene expression. Additional experiments were conducted on the HGL5 human granulosa cell line to assess mitochondrial function and metabolic reprogramming.
resultsMelatonin supplementation significantly improved IVF outcomes in women aged ≥ 38 years, increasing clinical pregnancy rates (46.0% vs. 20.3%, P < 0.01), ongoing pregnancy rates (36.5% vs. 15.3%, P < 0.01), and live birth rates (33.3% vs. 15.3%, P < 0.05). In cumulus cells from patients, gene expression analysis revealed that melatonin modulated cuproptosis and ferroptosis-related genes, including ATP7B and GPX4, with more pronounced effects in the ≥ 38 years group. This suggests melatonin enhances cellular resilience against oxidative stress and metal-induced toxicity in the ovarian microenvironment. In vitro studies using HGL5 cells showed melatonin reduced oxidative stress markers, improved mitochondrial function, restored expression of glycolysis and TCA cycle-related genes and modulated cuproptosis and ferroptosis-related gene expression. These findings provide mechanistic insight into melatonin's protective effects against regulated cell death in ovarian cells, potentially explaining the improved IVF outcomes observed.
conclusionsMelatonin supplementation significantly improved IVF outcomes in women of advanced maternal age, particularly those ≥ 38 years old, likely by modulating cuproptosis and ferroptosis and enhancing mitochondrial function in cumulus and granulosa cells. These results suggest that melatonin could be a promising adjuvant therapy for improving IVF success rates in older women.
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