Overview

Recent findings presented at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) indicate a significant connection between gut bacteria and an imbalance of amino acids in women diagnosed with polycystic ovary syndrome (PCOS). These factors may contribute to an increased risk of miscarriage and other adverse pregnancy outcomes.

Study Insights

The study reveals that women with PCOS show distinct differences in their gut microbiome and metabolic profiles, which are linked to premature aging of the endometrium and elevated risks for complications during pregnancy. Notably, researchers observed a significant decrease in the beneficial gut bacterium Parabacteroides merdae, alongside higher concentrations of branched-chain amino acids (BCAAs), particularly isoleucine, which is vital for protein synthesis and energy metabolism.

PCOS affects approximately one in five women of reproductive age worldwide and is a leading cause of infertility. Despite the effectiveness of fertility treatments for many women with PCOS, they frequently encounter complications such as miscarriage, preterm birth, and gestational diabetes. The underlying mechanisms contributing to this heightened risk have not been well understood until now.

Dr. Aixia Liu, the lead researcher, noted that even younger women with PCOS who achieve pregnancy still experience unexpectedly high rates of miscarriage and complications. This prompted an investigation into the interplay between gut microbiota, circulating metabolites, and uterine health.

Research Methodology

The prospective study tracked 220 women under 35 years across 44 cities in China, consisting of 110 women with PCOS and 110 matched controls. Utilizing gut microbiome sequencing and metabolomics, researchers profiled the differences between the two groups and examined laboratory studies on endometrial stromal cells (ESCs) to evaluate endometrial aging and decidualization, which is critical for successful embryo implantation.

The results revealed a marked reduction in microbial diversity in women with PCOS, particularly a decrease in the P. merdae species, which is associated with metabolic health. Serum metabolomic analysis indicated elevated levels of BCAAs, especially isoleucine, and reduced levels of short-chain fatty acids in the PCOS group.

Adverse Pregnancy Outcomes

Despite similar rates of conception, women with PCOS were found to be nearly twice as likely to experience at least one adverse pregnancy outcome, including miscarriage, preterm birth, low birth weight, gestational diabetes, hypertensive disorders, and perinatal death. Further studies indicated that isoleucine levels were also elevated in endometrial tissue. In laboratory settings, exposure of ESCs to isoleucine resulted in increased markers of cellular aging and reduced ability to undergo decidualization.

These findings suggest that aging-like changes in the uterus may occur earlier than expected, with high isoleucine levels and decreased P. merdae adversely affecting endometrial health, even in younger women.

Future Implications

The researchers propose that the presence of P. merdae and BCAAs could serve as potential biomarkers for identifying women with PCOS at higher risk for pregnancy complications, paving the way for personalized treatment strategies.

Dr. Liu emphasized the need for future studies to investigate whether dietary modifications, probiotics, or BCAA-restricted diets could reverse these adverse effects and enhance pregnancy outcomes. Professor Dr. Anis Feki, Chair-Elect of ESHRE, remarked that the evidence underscores the importance of addressing metabolic and microbial imbalances in PCOS to improve endometrial receptivity, particularly in younger women.

The study abstract will be published in the journal Human Reproduction.