(Paris, France, Monday, 30 June 2025) A new study presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE) reveals that women with polycystic ovary syndrome (PCOS) have distinct gut microbiota and metabolic signatures linked to premature endometrial ageing and a higher risk of adverse pregnancy outcomes.[1]
The research highlights a sharp reduction in the beneficial gut bacterium Parabacteroides merdae (P. merdae), alongside elevated levels of branched-chain amino acids (BCAAs), particularly isoleucine – an essential amino acid involved in protein production and energy metabolism. Together, these changes may act as potential drivers of poor endometrial function and reproductive complications in women with PCOS.
Affecting up to one in five women of reproductive age globally, PCOS is a major cause of infertility.[2] Although fertility treatments often succeed in helping women with PCOS conceive, they remain at higher risk of complications such as miscarriage, preterm birth, and gestational diabetes. Until now, the mechanisms behind this elevated risk have remained unclear.
“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 prospective study followed 220 women under the age of 35 across 44 cities in China, including 110 PCOS patients and 110 matched controls. Researchers used a combination of gut microbiome sequencing and metabolomics to profile differences between the groups and conducted laboratory studies on endometrial stromal cells (ESCs) to assess ageing and decidualisation, a process critical for embryo implantation.
Results showed a significant reduction in microbial diversity among PCOS patients, particularly a decrease in P. merdae, a species linked to metabolic health. Serum metabolomics revealed 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.
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.”
The researchers propose that P. merdae and BCAAs could serve as biomarkers for identifying high-risk PCOS patients and may guide personalised 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 personalised reproductive care in PCOS.”
The study abstract will be published today in Human Reproduction, one of the world’s leading reproductive medicine journals.
ENDS
Notes to editors:
A reference to the ESHRE Annual Meeting must be included in all coverage and/or articles associated with this study.
For more information or to arrange an expert interview, please contact the ESHRE Press Office at: press@eshre.eu
About the study author:
Dr. Aixia Liu is a Chief Physician specialising in reproductive endocrinology at the Women’s Hospital, School of Medicine, Zhejiang University.
Dr. Liu is an accomplished clinician and researcher with expertise in the complex cellular and molecular interactions at the maternal-fetal interface during pregnancy, ovarian function maintenance, and reproductive endocrinology. Her research contributes to advancing understanding in these areas of women's health.
About the European Society of Human Reproduction and Embryology
The main aim of ESHRE is to promote interest in infertility care and to aim for a holistic understanding of reproductive biology and medicine.
ESHRE collaborates world-wide and advocates universal improvements in scientific research, encourages and evaluates new developments in the field, and fosters harmonisation in clinical practice. It also provides guidance to enhance effectiveness, safety and quality assurance in clinical and laboratory procedures, psychosocial care, and promotes ethical practice. ESHRE also fosters prevention of infertility and related educational programmes and promotes reproductive rights regardless of the individual’s background. ESHRE’s activities include teaching, training, professional accreditations, mentoring and career planning for junior professionals, as well as developing and maintaining data registries. It also facilitates and disseminates research in human reproduction and embryology to the general public, scientists, clinicians, allied personnel, and patient associations.
Website: https://www.eshre.eu/
About Human Reproduction
Human Reproduction is a monthly journal of ESHRE and is one of the top three journals in the world in the field of reproductive biology, obstetrics and gynaecology. It is published by Oxford Journals, a division of Oxford University Press.
References:
[1] Liu, A., et al. (2025). Unraveling the interplay of gut microbiota, metabolic alterations, and endometrial senescence in polycystic ovary syndrome and its implications for adverse pregnancy outcomes. Human Reproduction.
[2] Azziz, R., Carmina, E., Chen, Z. et al. (2016). Polycystic ovary syndrome. Nat Rev Dis Primers 2, https://doi.org/10.1038/nrdp.2016.57.