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

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). In the resveratrol arm, 28 participants were randomized and 24 completed; participants were adult women aged 18 to 35 years with PCOS by Rotterdam criteria.

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.

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 protein (P = 0.0036), mtDNA copy number (P < 0.0001), and ATP content (P = 0.0014), while Nrf-1 was not significant (P = 0.0611). Clinically, the rate of mature oocytes was 78.04 ± 10.56 and the rate of high-quality embryos was 75.23 ± 5.648; chemical pregnancy was 45.83% (11/24) and clinical pregnancy was 37.50% (9/24), with no reported side effects.

The trial was small, single-center, and short in duration, with only 24 completers in the resveratrol arm. Several clinically important endpoints did not change significantly, including retrieved oocytes, fertilization rate, total embryos, and pregnancy rates, so the findings need confirmation in larger studies.