Trinity study reveals how the uterine microbiome may impact pregnancy success

Posted on: 06 July 2026

Among the key findings was one notable surprise, which suggests the biological signals that have long been used to govern the timing of embryo transfer may be misleading.

The study examined women with unexplained infertility who underwent ART and found that those who did not become pregnant had a different endometrial microbiome (the collection of microbes associated with the lining of the uterus) compared with women who achieved pregnancy. 

In particular, women with unsuccessful treatment outcomes had a more diverse microbiome, with fewer beneficial Lactobacillus bacteria and higher levels of other bacterial species.

Unexpectedly, the researchers also discovered that women who did not become pregnant showed higher levels of gene expression for several genes that are commonly used as markers of endometrial receptivity, which is the state in which the uterus is considered ready to receive an embryo. These markers are widely studied in fertility medicine and are sometimes used to help identify the optimal timing for embryo transfer, meaning the new result calls into question how effective this forecasting method is likely to be.

“The surprising finding was that higher expression of receptivity markers did not translate into better pregnancy outcomes,” said Dr Federica Giangrazi, from Trinity’s School of Biochemistry and Immunology, who is first author of the study that was recently published in Human Reproduction, a leading journal in the field of fertility medicine. 

“Our results suggest that when it comes to these markers, more is not necessarily better.”

To try to understand things better, the team investigated butyrate, a molecule produced by certain bacteria found in the endometrium. Using lab models that mimic the conditions of embryo implantation, they showed for the first time that butyrate can directly increase the expression of receptivity markers. 

However, butyrate also promoted inflammation and weakened the barrier function of endometrial cells. These changes could thus interfere with successful implantation.

What is the potential impact of this research?

The findings build on previous work by the same research group in Trinity’s School of Biochemistry and Immunology and Merrion Fertility Clinic at the National Maternity Hospital, showing that inflammation plays a critical role in fertility. 

Together, the studies suggest that pregnancy success depends on a delicate balance between the immune environment of the uterus and the composition of its microbiome, and that timing the point of embryo transfer to maximise the chance of successful implantation is not as easy as might have been assumed.

“While the research was conducted in a relatively small patient cohort and further studies are needed, the results highlight the potential importance of considering both the endometrial microbiome and inflammation when evaluating fertility,” said senior author, Prof. Cliona O’Farrelly, from Trinity’s School of Biochemistry and Immunology. 

“In the future, a better understanding of these interactions could help clinicians identify which patients are most likely to benefit from specific ART strategies and improve the timing of embryo transfer.”

The study can be read on the Human Reproduction website. The work was supported by a grant for Fertility Innovation from Merck KGaA.

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