The impact of resveratrol on the outcome of the in vitro fertilization: an exploratory randomized placebo-controlled trial

Abstract

Background Resveratrol is a natural polyphenolic compound present in plants and red wine with many potential health benefits. This compound has various anti-inflammatory and anti-tumor properties and can improve cellular mitochondrial activity. This trial was designed to evaluate the effect on the outcome of IVF of Resveratrol supplementation in women > 35 years with good ovarian reserve (AMH > 1.2 ng/ml). Women were randomized to receive or placebo or Resveratrol (150 mg per day) for three months preceding the ovarian stimulation (OS). All patients were stimulated with a starting dose of recombinant FSH ranging between 150 and 300 IU according to age and ovarian reserve. GnRH antagonist flexible protocol was adopted for pituitary suppression. Triggering was performed with urinary hCG (10.000 IU). Results The study was conducted between January 2019 and December 2022 with aa total of 37 cases and 33 controls were recruited. No statistically significant differences in the number of oocytes retrieved, biochemical pregnancy, clinical pregnancy and live birth rates were observed between women treated with resveratrol and control group. A statistically significant increase in the follicle output rate (FORT) and follicle-to oocyte index (FOI) was observed in women treated with resveratrol-based nutraceutical (0.92 versus 0.77 [p = 0.02], and 0.77 versus 0.64 [p = 0.006], respectively). Conclusions Preliminary results from this study indicate that pre-treatment with resveratrol may improve ovarian sensitivity to exogenous FSH, which in turn may decrease the risk of hypo-response to OS in advanced reproductive age women.

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

“…In addition, fertilization and pregnancy outcomes can be significantly affected by the quality and maturity of gametes, uterine receptivity, and competence of the embryologist [ 66 ]. In this context, our findings align with those of previous clinical trials [ 18 , 19 , 64 , 67 ]. However, some researchers reported contradictory results, highlighting the detrimental effect of resveratrol on the clinical pregnancy rate [ 68 ].…”

“…In their study, resveratrol was administered during the luteal phase of the treatment cycle, and this adverse effect was likely attributed to its impact on the suppression of decidual senescence. The discrepancy between our trial and another study, which used a low dose of resveratrol (200 mg daily), may be due to the various treatment durations, heterogeneous populations, retrospective design, and different IVF protocols used [ 67 ]. More specifically, in our trial, resveratrol was administered before and during ovarian stimulation, and intake was discontinued on the day of oocyte retrieval.…”

Electro-Metabolic Coupling of Cumulus–Oocyte Complex

“…It can be hypothesized that resveratrol, affecting the electro-metabolic coupling between the cells of the oophorous cumulus and the oocyte, could have a significant positive effect on CCs, from which an improvement in ovarian physiology and oocyte development could be of benefit altogether. The modulation of electro-metabolic coupling of COC by resveratrol could explain the beneficial effect on fertility of women undergoing IVF [218][219][220][221]. It can also be hypothesized that the role of mitochondria present in the CCs may affect the maturation and competence of the oocyte, especially in the early stages of folliculogenesis, since the primordial follicle appears to be small and well irrorated.…”