Resveratrol ameliorates mitochondrial biogenesis and reproductive outcomes in women with polycystic ovary syndrome undergoing assisted reproduction: a randomized, triple-blind, placebo-controlled clinical trial
What this study found
Resveratrol improved follicular oxidative balance and mitochondrial biogenesis and was associated with better oocyte maturity and high-quality embryo outcomes, but it did not significantly improve retrieval, fertilization, total embryo, or pregnancy outcomes. In follicular fluid, TAC was 1.487 ± 0.3257, TOS was 1.885 (0.2490-2.422), and OSI was 1.074 ± 0.9181, with significant improvements versus placebo (TAC P = 0.0009, TOS P = 0.0142, OSI P = 0.0039). Mitochondrial-related markers also improved, including PGC-1α mRNA (P = 0.0032), TFAM mRNA (P = 0.0003), SIRT1 protein (P < 0.0001), PGC-1α…
- Study & population
- Randomized, triple-blind, placebo-controlled clinical trial in women with polycystic ovary syndrome undergoing intracytoplasmic sperm injection at Omid Fertility Clinic in Tehran, Iran (enrollment February 2023 to December 2023).
- Intervention
- Resveratrol was given orally as 800 mg/day of trans-resveratrol (99% purified; two 400 mg capsules daily) for 60 days before oocyte collection, compared with placebo.
- Key limitation
- The trial was small, single-center, and short in duration, with only 24 completers in the resveratrol arm.
Original abstract
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). 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. 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). These findings indicate that resveratrol may be a promising therapeutic agent for patients with PCOS undergoing assisted reproduction. http://www.irct.ir; IRCT20221106056417N1; 2023 February 09.