Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial.

Negar Ajabi Ardehjani, Marzieh Agha-Hosseini, Maryam Shabani Nashtaei, Mahshad Khodarahmian, Maryam Shabani, Masoome Jabarpour, Farzane Fereidouni, Tayebeh Rastegar, Fardin Amidi

Journal: Journal of ovarian research 2024;17(1):143

PMID: 38987824

Plain Language Summary

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Polycystic ovary syndrome is an endocrine disorder which may be mediated by mitochondrial dysfunction. The aim of this clinical trial was to investigate the potential benefits of resveratrol, a polyphenol found in grapes and berries, on oxidative stress, mitochondrial biogenesis and assisted reproductive technique (ART) outcomes in PCOS patients. 56 women with PCOS and undergoing intracytoplasmic sperm injection (ICSI) treatment were enrolled in this triple-blind, randomised controlled trial. Participants took 800 mg resveratrol per day or placebo for 60 days. Primary outcome was oxidative stress in the follicular fluid (FF), secondary outcomes included biomarkers for mitochondrial biogenesis in granulosa cells, as well as ART outcomes. Markers of oxidative stress and mitochondrial biogenesis were significantly improved in the intervention as compared to the control group. The resveratrol group also had significantly better oocyte maturity rate and percentage of high-quality embryos. There were no statistical differences in other ART outcome measures (number of retrieved oocytes, number of MII oocytes, total number of embryos, number of fertilized oocytes, fertilization rate, chemical or clinical pregnancy rate). The authors conclude that resveratrol may hold promise for women with PCOS undergoing ART.

Abstract

BACKGROUND

This study was designed to examine the effect of resveratrol on mitochondrial biogenesis, oxidative stress (OS), and assisted reproductive technology (ART) outcomes in individuals with polycystic ovary syndrome (PCOS).

METHODS

Fifty-six patients with PCOS were randomly assigned to receive 800 mg/day of resveratrol or placebo for 60 days. The primary outcome was OS in follicular fluid (FF). The secondary outcome involved assessing gene and protein expression related to mitochondrial biogenesis, mitochondrial DNA (mtDNA) copy number, and adenosine triphosphate (ATP) content in granulosa cells (GCs). ART outcomes were evaluated at the end of the trial.

RESULTS

Resveratrol significantly reduced the total oxidant status (TOS) and oxidative stress index (OSI) in FF (P = 0.0142 and P = 0.0039, respectively) while increasing the total antioxidant capacity (TAC) (P < 0.0009). Resveratrol consumption also led to significant increases in the expression of critical genes involved in mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator (PGC-1α) and mitochondrial transcription factor A (TFAM) (P = 0.0032 and P = 0.0003, respectively). However, the effect on nuclear respiratory factor 1 (Nrf-1) expression was not statistically significant (P = 0.0611). Resveratrol significantly affected sirtuin1 (SIRT1) and PGC-1α protein levels (P < 0.0001 and P = 0.0036, respectively). Resveratrol treatment improved the mtDNA copy number (P < 0.0001) and ATP content in GCs (P = 0.0014). Clinically, the resveratrol group exhibited higher rates of oocyte maturity (P = 0.0012) and high-quality embryos (P = 0.0013) than did the placebo group. There were no significant differences between the groups in terms of chemical or clinical pregnancy rates (P > 0.05).

CONCLUSIONS

These findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction.

TRIAL REGISTRATION NUMBER

http://www.irct.ir ; IRCT20221106056417N1; 2023 February 09.

© 2024. The Author(s).

Address: Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Department of Infertility, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Department of Infertility, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran.; Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.; Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. [email protected].; Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. [email protected].; Department of Infertility, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran. [email protected].

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