
(Paris, France, Monday, 30 June 2025) A groundbreaking study presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) has unveiled new insights into the complex relationship between gut bacteria, metabolic imbalances, and reproductive health in women with polycystic ovary syndrome (PCOS). The research reveals distinct gut microbiota and metabolic signatures in these women, which are linked to premature endometrial ageing and a heightened risk of adverse pregnancy outcomes.
The study highlights a notable reduction in the beneficial gut bacterium Parabacteroides merdae (P. merdae) and elevated levels of branched-chain amino acids (BCAAs), particularly isoleucine. This essential amino acid plays a crucial role in protein production and energy metabolism. Together, these changes may contribute to poor endometrial function and reproductive complications in women suffering from PCOS.
Understanding PCOS and Its Implications
PCOS affects up to one in five women of reproductive age globally, making it a significant cause of infertility. Although fertility treatments often help women with PCOS conceive, they continue to face higher risks of complications such as miscarriage, preterm birth, and gestational diabetes. The mechanisms behind these elevated risks have remained largely unclear until now.
“In clinical practice, we noticed that even younger women with PCOS who achieved pregnancy still faced unexpectedly high rates of miscarriage and other complications,” said Dr. Aixia Liu, the lead author of the study. “Many of these women also had metabolic imbalances and digestive issues, which led us to explore the possible interplay between the gut microbiota, circulating metabolites, and the uterus.”
The Study’s Methodology and Findings
The prospective study followed 220 women under the age of 35 across 44 cities in China, including 110 PCOS patients and 110 matched controls. Researchers employed a combination of gut microbiome sequencing and metabolomics to profile differences between the groups. Laboratory studies on endometrial stromal cells (ESCs) were conducted to assess ageing and decidualisation, a process critical for embryo implantation.
Results revealed a significant reduction in microbial diversity among PCOS patients, particularly a decrease in P. merdae, a species linked to metabolic health. Serum metabolomics showed elevated levels of BCAAs, especially isoleucine, and reduced levels of short-chain fatty acids in the PCOS group.
Despite similar pregnancy rates, women with PCOS were nearly twice as likely (1.95 times) to experience at least one adverse pregnancy outcome, including miscarriage, preterm birth, macrosomia, low birth weight, gestational diabetes, hypertensive disorders, and perinatal death.
Exploring the Role of Isoleucine
Further investigation revealed that isoleucine levels were also elevated in endometrial tissue. When researchers exposed ESCs to isoleucine in the lab, they observed increased markers of cellular senescence and reduced capacity for decidualisation. “These findings indicate ageing-like changes in the uterus, occurring much earlier than expected,” said Dr. Liu. “Our data suggest that high isoleucine levels and the loss of P. merdae may impair endometrial health, even in women under 35.”
Future Directions and Potential Interventions
The researchers propose that P. merdae and BCAAs could serve as biomarkers for identifying high-risk PCOS patients and may guide personalized treatment approaches in the future. “The next step is to explore whether dietary interventions, probiotics, or BCAA-restricted diets can reverse these effects and improve pregnancy outcomes,” concluded Dr. Liu.
Professor Dr. Anis Feki, Chair-Elect of ESHRE, added, “The study provides compelling evidence that metabolic and microbial imbalances in PCOS are not only systemic but may directly impair endometrial receptivity, even in younger women. These findings mark a critical step toward personalized reproductive care in PCOS.”
The study abstract will be published today in Human Reproduction, one of the world’s leading reproductive medicine journals. As the scientific community continues to unravel the complexities of PCOS, these findings offer a promising avenue for improving reproductive outcomes and enhancing the quality of life for millions of women worldwide.