News | Study Links Gut Microbiome Imbalance to Pregnancy Risks in Women With PCOS



News | Study Links Gut Microbiome Imbalance to Pregnancy Risks in Women With PCOS


A study presented at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology found substantial changes in the gut microbiome and metabolic profile of women with polycystic ovary syndrome (PCOS). These changes were closely associated with premature endometrial aging and a higher risk of adverse pregnancy outcomes, suggesting new approaches to personalized fertility management.


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A hidden link between gut bacteria and pregnancy risk

The Chinese study included 220 women under 35 across 44 cities in China: 110 with PCOS and 110 age- and weight-matched controls. Combined microbiome sequencing and metabolomic analysis found markedly reduced gut diversity among women with PCOS, especially a substantial loss of the beneficial bacterium Parabacteroides merdae (P. merdae).


Blood levels of branched-chain amino acids (BCAAs), particularly isoleucine, were significantly higher, while beneficial short-chain fatty acids were lower. Researchers treated human endometrial stromal cells (ESCs) with isoleucine in the laboratory. Markers of cellular aging increased and decidualization capacity declined, indicating premature endometrial aging.


"Even young women with PCOS face an unusually high rate of adverse outcomes after becoming pregnant, which deserves serious clinical attention," said project leader Dr. Liu Aixia.


Risk of adverse pregnancy outcomes nearly doubled

Although pregnancy rates were similar between groups, women with PCOS were 1.95 times as likely to experience at least one adverse outcome. These included miscarriage, preterm birth, macrosomia, low birth weight, gestational diabetes, hypertensive disorders of pregnancy, and perinatal death.


High isoleucine levels were also found in endometrial tissue, further supporting a direct local effect.


Future direction: Can the changes be treated or reversed?

The team proposes that loss of P. merdae and elevated isoleucine could become biomarkers for identifying high-risk patients with PCOS. The next stage will examine whether dietary interventions, probiotics, or BCAA-restricted diets can restore the uterine environment and improve pregnancy rates.


ESHRE President-Elect Prof. Anis Feki commented: "This study offers a new explanation for adverse pregnancy risk in women with PCOS—not only metabolic abnormalities, but potentially reversible changes in the uterine environment itself."


Clinical implications: Toward personalized reproductive care for PCOS

PCOS has long been considered an endocrine-metabolic disorder characterized mainly by ovulatory dysfunction. This study suggests its effects on the uterine environment may begin well before symptoms appear and operate through metabolic and microbial mechanisms.


"Our study creates possibilities for personalized reproductive interventions," Dr. Liu concluded. "We hope measurable and treatable markers will help women with PCOS identify risks earlier and extend the endometrium's healthy window."


Source:

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