Preconception resveratrol intake against infertility: Friend or foe?

Abstract

Background: Resveratrol is an antiaging, antioxidant, anti-inflammatory, and insulin-sensitizing natural polyphenolic compound. Growing evidence indicates that resveratrol has potential therapeutic effects in infertile women with diminished ovarian function, polycystic ovary syndrome (PCOS), or endometriosis. However, only one clinical trial in women undergoing in vitro fertilization (IVF) cycles using resveratrol has ever been reported. This review focuses on the potential therapeutic effects of resveratrol on pregnancy and on its advantages and disadvantages in pregnancy outcomes during infertility treatment.

Methods: We performed a literature review to describe the known impacts of resveratrol on the ovary and endometrium.

Results: Resveratrol upregulates sirtuin (SIRT)1 expression in ovaries, which is associated with protection against oxidative stress. It leads to the activation of telomerase activity and mitochondrial function, improving ovarian function. In the endometrium, resveratrol downregulates the CRABP2-RAR pathway leading to suppressing decidual and senescent changes of endometrial cells, which is essential for embryo implantation and placentation. Moreover, resveratrol may also induce deacetylation of important decidual-related genes.

Conclusions: Resveratrol has potential therapeutic effects for improving ovarian function; however, it also has anti-deciduogenic actions in uterine endometrium. In addition, its teratogenicity has not yet been ruled out; thus, resveratrol should be avoided during the luteal phase and pregnancy.

Keywords: aging; assisted reproductive technology; infertility; resveratrol; sirtuin.

Figure 1

Effects of resveratrol on human health. Resveratrol has beneficial effects on human health, including antiaging, antioxidant, anti‐inflammatory, insulin‐sensitizing, cardioprotective, vasodilating, and anti‐neoplastic properties

Figure 2

Effects of resveratrol on ovaries and endometrium. Resveratrol upregulates ovarian SIRT1 expression, which is associated with protection against oxidative stress and glycation stress. Moreover, it activates telomerase activity and mitochondrial function, improving ovarian function. In the decidualized endometrium, resveratrol accelerates downregulation of CRABP2‐RAR pathway, inhibiting decidual senescence and decidualization. In addition, resveratrol may also induce deacetylation of important decidual‐related genes. Up‐ and down‐arrowheads: promotive and inhibitive actions

Figure 3

Pre‐treatment with resveratrol does not inhibit decidual marker genes in the decidualized endometrium. Real‐time quantitative PCR analysis of decidual markers PRL and IGFBP1 in human endometrial stromal cells (treated with 8‐bromoadenosine‐cAMP and progesterone (P4) with or without 100 μmol/L of resveratrol for 4 or 8 days and pre‐treatment of the cells with resveratrol for 48 h followed by wash‐off and decidualization without resveratrol treatment) showing fold changes (mean ± SEM) in PRL and IGFBP1 transcript levels relative to negative control (from four independent primary cultures). Different letters above the error bars suggest groups that are significantly different from each other at P < .05. This is a modified graph from our previous reports (Ochiai et al 56)

Figure 4

Recommendations for resveratrol supplementation in IVF treatment. We recommend discontinuation of resveratrol intake at the beginning of the luteal phase (the day of ovulation) or cryopreservation of all embryos (freeze‐all policy) and vitrified and warmed ET without supplementation