Resveratrol for infertility: A frenemy?

Resveratrol has disparate effects on ovarian functions and endometrium.

Key Points

Highlights:

• Resveratrol has potential therapeutic effects for improving ovarian functions but at the same time, it also has anti-deciduogenic actions on endometrium that could cause implantation failure.

Importance: 

• Besides promising beneficial effects of resveratrol on obtaining good quality oocytes, Resveratrol adversely affects implantation hence pregnancy due to the impairment of endometrial receptivity.

What's done here:

• The authors performed a literature review to define the known impacts of resveratrol on the ovary and endometrium.
• The potential therapeutic effects of resveratrol on infertile patients and possible outcomes during their pregnancy were also reviewed.

Background:

• Resveratrol is an anti-aging, anti-oxidant, anti-inflammatory, insulin-sensitizing, cardioprotective, vasodilating, and anti-neoplastic natural polyphenolic compound. 
• It can be detected in a variety of plants, food, and drinks such as grapes, nuts, cranberries, and red wine. 
• Resveratrol supplementation helps to improve metabolic disorders, obesity, diabetes mellitus, hypertension, and reduce the risk of cardiovascular disease as well as malignant neoplasms.    
• There is growing evidence that resveratrol diminishes ovarian function in some diseases as a polycystic ovarian syndrome (PCOS), uterine fibroids, and endometriosis.   
• No literature information on the relation of resveratrol and infertility, except for one clinical trial on women undergoing in vitro fertilization (IVF).

Key results:

• Resveratrol upregulates longevity gene sirtuin (SIRT)1 gene expression in ovaries and protects against oxidative stress.
• Activates telomerase and mitochondrial function, and improves ovarian failures.
• To the interest of infertile couples, it can improve testicular function and sperm quality.
• However, it also has the undesired effect of downregulating the CRABP2-RAR pathway in the endometrium that causes to suppress decidua and senescence that is essential for implantation and placentation.
• Another negative effect of Resveratrol is inducing the deacetylation of important decidual related-genes.

Lay Summary

Ovarian aging is defined by an age-specific decline of the functional ovarian reserve. Female ovarian reserve declines progressively with increasing chronological age.

Chronic damage by reactive oxygen species results in deterioration and aging through mitochondrial dysfunction, telomere shortening, cohesion dysfunction, and spindle instability known as "genetic and environmental factors". To slow down this procedure, a natural compound, "Resveratrol" can be used based on its anti-aging, anti-inflammatory, antioxidant, anti-neoplastic, cardioprotective, vasodilatation, and insulin-sensitizing effects.

Despite the beneficial effects of Resveratrol on human health, and the information that Resveratrol supplementation helps to treat infertility based on animal studies, there is a paucity of clinical trials especially on infertile couples suffering from PCOS, endometriosis, and primary ovarian failure.

Ochiai and al. from the Department of Obstetrics and Gynecology of Juntendo University, Japan, planned to draw attention to this issue and recently published their discussions and recommendations about the topic, through a literature review in "Reproductive Medicine and Biology".

Previous research proved the beneficial anti-oxidative stress effect of resveratrol on primary ovarian failure in rats and show that it may protect the ovarian reserve against aging via SIRT1 activation, resulting in prolonged ovarian life span. Resveratrol was also shown to help as a therapeutic supplement; that has not yet been proven in humans.

A randomized double-blind clinical trial in women with PCOS indicated that resveratrol is a candidate novel treatment against PCOS, as resveratrol administration significantly decreased total testosterone, dehydroepiandrosterone sulfate, fasting insulin levels and repaired the insulin sensitivity index. The fertility outcome of PCOS patients treated with resveratrol was not evaluated. Treating the culture media of both animal and human oocytes with resveratrol improves oocyte maturation, helps to develop competent embryos and blastocysts, and protect against the postovulatory aging when used in IVF cycles for successful pregnancies. However, data for human studies are still not enough for the supplement of resveratrol in IVF cycles.

Endometrial receptivity with optimal decidualization and synchronization with developmentally competent embryos are two important processes for a successful pregnancy. Although in vitro studies showed that the antiapoptotic and antiproliferative effects of resveratrol can inhibit endometriosis, the fact that resveratrol may inhibit decidual senescence leading to a decreased endometrial receptivity was supported by the authors in the clinical practice in an earlier study: The authors clinical trial using resveratrol in their IVF-ET cycles demonstrated that resveratrol intake was significantly associated with low clinical pregnancy rates.

The authors concluded that "Furthermore, the teratogenicity of has not yet been ruled out; therefore, resveratrol should be avoided during the luteal phase and pregnancy. Further clinical studies are needed to establish optimal doses and periods of resveratrol intake while preventing adverse effects on implantation, subsequent pregnancy, and the fetus".

Research Source: https://pubmed.ncbi.nlm.nih.gov/32273814/?from_term=endometriosis&from_sort=date&from_size=100&from_pos=60