Road to Fertility

Your guide to trying to conceive, fertility treatments, genetic testing and your path to pregnancy

Endometritis: no symptoms, no problem?

What is chronic endometritis?

Chronic endometritis (CE), not to be confused with endometriosis, is a persistent inflammation of the lining of the uterus – the endometrium. The root cause of endometritis is a chronic infection of the uterine cavity, most frequently by pathogenic (disease causing) bacteria in the microbial environment of the endometrium – often referred to as a pathogenic endometrial microbiome.  

In some cases of CE, vague symptoms may be present, including abnormal vaginal bleeding or discharge, abdominal swelling and fever. However, in most cases, chronic endometritis is asymptomatic. The absence of symptoms can cause patients to dismiss the risks of endometritis, but CE can have a lasting effect on your fertility and general health and should be taken very seriously.

Endometritis and fertility

A woman holds soil with a growing seedling, representing the importance of a healthy seed (embryo) and soil (endometrium).

The analogy that I find best explains the role of the endometrium in fertility is the seed and the soil:

  • To nurture the first growth of a seedling, you must begin with a healthy seed and plant it in fertile soil
  • If the soil – the endometrium – is not ready, or is a hostile environment, then the seed – the embryo – will not succeed in developing into a healthy pregnancy

Chronic endometritis causes an incredibly hostile environment for an embryo!

The link between CE and fertility issues has been well documented in scientific literature: the prevalence of chronic endometritis in the general population is approximately 10%1this increases to approximately 30% in infertile women, and as high as 60% in patients with recurrent miscarriage2.

Classical diagnosis of chronic endometritis

A photo of the endometrium viewed through a microscope, for histological investigation of endometritis.

A recent study3 of the diagnosis of chronic endometritis, led by Dr Inmaculado Moreno, highlights the notorious difficulty of diagnosing CE – the current ‘classical’ methods for diagnosis are:

  1. Histology – a sample of tissue is taken and examined under a microscope
  2. Hysteroscopy – a small camera is inserted into the uterus and a visual examination takes place
  3. Microbial culture – a sample is taken from the endometrium, and an attempt is made to ‘grow’ the bacteria that are present

The flaws of classical diagnosis

The classical methods of diagnosis have flaws that impair their ability to reliably diagnose chronic endometritis:

  • Histological investigations and hysteroscopy are both dependent on subjective judgement, and numerous different diagnostic criteria exist
  • Histology typically underdiagnoses CE, whilst hysteroscopy usually overdiagnoses the disease
  • Depending on their location, between 20-60% of bacteria cannot be cultured

The effect of these varied diagnostic methods and their inherent flaws can lead to inconclusive or misleading results in 80% of cases3. The current ‘gold standard’ for diagnosing chronic endometritis is a combination of these three methodologies – requiring an invasive investigation (hysteroscopy) in addition to an endometrial biopsy.

A new approach to diagnosis

A circular picture of molecules, representing molecular microbiology for endometritis diagnosis.

Recent developments in genomics have led to significant reductions in both the time and cost associated with sequencing DNA. These technologies can be applied to the diagnosis of chronic endometritis through a methodology called molecular microbiology.

Diagnosis by molecular microbiology uses a technique called Next Generation Sequencing (NGS) to study the DNA that is present in an endometrial sample – specific markers in bacterial genes allow us to identify the specific bacteria present, and in what proportions.

The investigation3 by Dr Moreno’s team found that molecular microbiology using NGS is as effective at diagnosing chronic endometritis as the combined classical ‘gold standard’, whilst being quicker, less invasive and less costly.

Treatment – restoring a healthy endometrial microbiome

Given the important link between endometritis and fertility, it is important that, once diagnosed, CE can be effectively treated. Typical treatment will be a course of antibiotics, which can be carefully selected when the specific species of bacteria are identified through molecular microbiology.

Antibiotics, however, can also disrupt the healthy components of the endometrial microbiome – research4 has shown, for example, the importance of lactobacillus in providing the best environment for an embryo to develop. A probiotic follow-up treatment can be incredibly beneficial in restoring the endometrial microbiome to its healthiest, most fertile state.


Tests from Igenomix

Logos for the Igenomix EMMA and ALICE tests

Understanding all of the factors that influence your fertility success can be incredibly confusing. I hope that this introduction to this silent but serious condition helps you at least a small amount in taking charge of your fertility. At Igenomix, we offer two tests for the endometrial microbiome:

  • ALICE – Analysis of Infections Chronic Endometritis – which uses molecular microbiology through NGS to diagnose CE and recommend a treatment pathway (usually targeted antibiotics)
  • EMMA – Endometrial Microbiome Metagenomic Analysis – this test uses NGS to give a total overview of the overall health of the uterine cavity, including:
    • Percentage of Lactobacilli
    • Percentages of the ten most abundant bacteria detected
    • Whether the overall endometrial microbiome is normal or abnormal
    • An ALICE test for CE (see above)
    • Recommended targeted antibiotic/probiotic therapy
  • EndomeTRIO – combines EMMA and ALICE with our test for endometrial receptivity, ERA

If you would like more information, then please do get in touch with our specialist team.


References

1. Park, Hyun Jong et al. “Chronic endometritis and infertility” Clinical and experimental reproductive medicine vol. 43,4 (2016): 185-192 doi: 10.5653/cerm.2016.43.4.185

2. Cicineli, E. et al. “Chronic endometritis due to common bacteria is prevalent in women with recurrent miscarriage as confirmed by improved pregnancy outcome after antibiotic treatment” Reproductive Sciences vol. 21,5 (2014): 640-647 doi: 10.1177/1933719113508817

3. Moreno, I. et al. “The diagnosis of chronic endometritis in infertile asymptomatic women: a comparative study of histology, microbial cultures, hysteroscopy, and molecular microbiology” Am J Obstet Gynecol vol. 218,6 (2018): 602 doi: 10.1016/j.ajog.2018.02.012

4. Moreno, I. et al. “Evidence that the endometrial microbiota has an effect on implantation success or failure” Am J Obstet Gynecol vol. 215,6 (2016): 684-703 doi: 10.1016/j.ajog.2016.09.075

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