Can your microbiome affect IVF success?

Medically reviewed by Mr. Ozkan Ozturk, consultant gynaecologist and specialist in reproductive medicine, CRGH.

When you’re trying to conceive, it’s natural to focus on things like egg quality, sperm quality and embryo development. 

But there is another part of the fertility picture that researchers are increasingly interested in: the reproductive microbiome. 

New research presented at the recent European Society of Human Reproduction and Embryology (ESHRE) conference continues to build our understanding of how the bacteria living within the reproductive tract may influence implantation and pregnancy. 

In this blog, Dr Ozkan Ozturk, Consultant Gynaecologist and Specialist in Reproductive Medicine at CRGH, explains what the latest evidence tells us, why the endometrial microbiome is attracting so much attention, and what it could mean for patients undergoing fertility treatment. 

What is the reproductive microbiome? 

Our bodies are home to trillions of naturally occurring bacteria, fungi and other microorganisms. Together, these are known as the microbiome. 

Although we often associate bacteria with infection, many bacteria are beneficial and help keep different parts of the body healthy. The reproductive tract is no exception. 

Both the vagina and the lining of the uterus (known as the endometrium) have their own bacterial communities. In a healthy reproductive tract, these communities are often rich in bacteria called Lactobacillus, which help support a healthy local environment. 

Sometimes however, the balance of these bacteria can become disrupted. This is known as dysbiosis. 

Research suggests that dysbiosis may contribute to inflammation and changes in the local immune environment, which may in turn affect reproductive health. 

Around one in four women may have an imbalance in the vaginal microbiome. 

This doesn’t always cause obvious symptoms, so you might not necessarily know that the balance has changed. 

What’s the difference between the vaginal and endometrial microbiome? 

It might seem logical to assume that if the vaginal microbiome is healthy, the microbiome inside the uterus will be healthy too. But it isn’t quite that simple.  The vagina and uterus are connected, and bacteria can move from the lower reproductive tract upwards. However, they are still different environments with their own levels of acidity, oxygen, nutrients and immune activity. 

Studies have found that there can be a difference between vaginal and endometrial microbiome profiles in around 5% of cases – roughly one in 20. This means that a vaginal sample can provide useful information about the reproductive tract but it might not always tell us exactly what’s happening inside the uterus. 

The vagina and uterus are connected, but they don’t always tell us the same story. 

Why does the endometrial microbiome matter? 

The endometrium is the lining of the uterus and the place where an embryo implants. 

We often talk about embryo quality when discussing IVF success but the environment the embryo is placed into matters too. Successful implantation relies on a carefully balanced interaction between the embryo, the endometrium and the immune system.  

Researchers are therefore looking closely at whether the bacteria present within the uterus could influence that environment.  Studies have associated an imbalance in the endometrial microbiome – particularly lower levels of beneficial Lactobacillus bacteria alongside increased levels of potentially harmful bacteria – with: 

•  Recurrent implantation failure 
• Recurrent miscarriage 
• Lower pregnancy rates following fertility treatment 

By contrast, a Lactobacillus-dominant endometrium has been associated with higher live birth rates. 

That doesn’t mean the microbiome is responsible for every unsuccessful embryo transfer or miscarriage. But for selected patients, assessing the endometrial environment may provide another useful piece of the puzzle. 

Can an unhealthy microbiome affect IVF success? 

An imbalance in vaginal bacteria has been associated with reproductive health problems including some infections, early pregnancy loss and lower clinical pregnancy rates. 

However, simply treating vaginal dysbiosis before embryo transfer has not consistently been shown to improve IVF outcomes. 

This is one reason why researchers are increasingly interested in looking directly at the endometrium rather than assuming that the vaginal microbiome accurately reflects what is happening inside the uterus. 

Does treating the endometrial microbiome improve IVF outcomes? 

Some studies of patients who’ve undergone Endometrial Microbiome Metagenomic Analysis (EMMA) have reported higher clinical pregnancy and live birth rates per embryo transfer compared with patients who weren’t tested. 

There is also preliminary evidence suggesting that when an abnormal endometrial microbiome is identified, treated and restored to a healthier balance, subsequent pregnancy outcomes may become comparable with those seen in patients who had a healthy microbiome from the outset. 

These findings are encouraging but the evidence is still developing and further high-quality research is needed. 

How does CRGH assess the microbiome? 

At CRGH, we take a comprehensive approach when investigating recurrent implantation failure and recurrent miscarriage. 

Where clinically appropriate, assessment of the endometrial and vaginal microbiome sometimes forms part of our wider evaluation of endometrial health. 

 This might include: 

•  EMMA (Endometrial Microbiome Metagenomic Analysis), which evaluates the balance of bacteria within the endometrium. 
• ALICE (Analysis of Infectious Chronic Endometritis), which looks for bacteria associated with chronic endometritis. 
• Vaginal microbiome assessment to give us useful information about bacteria in the lower reproductive tract.  

 Who might benefit from microbiome testing? 

Microbiome testing is not something every fertility patient needs. Your consultant may discuss it with you if you’ve experienced: 

•  Recurrent implantation failure 
• Recurrent miscarriage 
• Several unsuccessful IVF cycles without a clear explanation 
• Suspected chronic endometritis 

If testing identifies an abnormal microbiome, your consultant will talk you through the results and explain whether treatment is appropriate. 

The next steps will depend on what has been identified and your individual circumstances. 

Where treatment is recommended, the aim is to address potentially harmful bacteria and support a healthier environment before embryo transfer.  

Looking at the bigger picture 

Implantation and pregnancy can be influenced by many factors, and the reproductive microbiome is only one part of a much bigger fertility picture.   

At CRGH, microbiome testing is about understanding another part of the environment in which implantation takes place and using that information to help personalise your care. 

If you’d like to understand whether microbiome testing could be relevant to your fertility journey, speak to your CRGH consultant.  They can explain the available investigations, the current evidence and whether testing is appropriate for your individual circumstances.