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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).)

Background: Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during frozen embryo transfer (FET) cycles. However, still the questions regarding the maximum threshold level, and the highest allowed dosage of hormonal medications remain unresolved. The present study was conducted to determine whether there is any relationship between the serum progesterone and estradiol levels on the day of ET, and live birth rate (LBR) in patients receiving HRT in FET cycles., Methods: In this prospective cohort study, eligible women who were undergoing their first or second FET cycles with the top graded blastocyst stage embryos were included. All patients received the same HRT regimen. FET was scheduled 5 days after administration of the first dosage of progesterone. On the morning of ET, 4-6 h after the last dose of progesterone supplementation, the serum progesterone (P 4, ng/ml) and estradiol (E 2 , pg/ml) levels were measured., Results: Amongst the 258 eligible women that were evaluated, the overall LBR was 34.1 % (88/258). The serum P 4 and E 2 values were divided into four quartiles. The means of women's age and BMI were similar between the four quartiles groups. Regarding both P 4 and E 2 values, it was found that the LBR was significantly lower in the highest quartile group (Q 4 ) compared with the others, (P = 0.002 and P = 0.042, respectively). The analysis of the multivariable logistic regression showed that the serum level of P 4 on ET day, was the only significant predictive variable for LBR. The ROC curve revealed a significant predictive value of serum P 4 levels on the day of ET for LBR, with an AUC = 0.61 (95 % CI: 0.54-0.68, P = 0.002). The optimum level of serum P 4 , with 70 % sensitivity and 50 %specificity for LBR, was 32.5 ng/ml., Conclusions: The present study suggests that a serum P4 value at the maximum threshold on the day of FET is associated with reduced LBR following blastocyst transfer. Therefore, measuring and monitoring of P 4 levels during FET cycles might be necessary. However, the results regarding the necessity for the screening of serum E 2 levels before ET, are still controversial, and further prospective studies are required.