19/10/2026
❤️ Recurrent Miscarriage & Recurrent Implantation Failure
Could inflammation in the lining of the womb be contributing to the problem?
When a woman experiences repeated miscarriages or several unsuccessful IVF embryo transfers, it is natural to want to understand why.
For some women, the cause may involve the lining of the womb — the endometrium.
But there is an important distinction between finding bacteria within the endometrium and demonstrating that the endometrium is actually inflamed.
Finding bacteria does NOT necessarily mean that a woman has endometritis.
This is one of the key differences between microbiome tests such as EMMA and ALICE and the Reprognostics Comprehensive 4-Marker Endometrial Biopsy.
🔬 EMMA and ALICE — What do they actually tell us?
EMMA (Endometrial Microbiome Metagenomic Analysis) and ALICE (Analysis of Infectious Chronic Endometritis) examine the bacterial environment of the endometrium.
EMMA assesses the presence and relative abundance of different bacteria, including Lactobacillus species, which are generally considered beneficial.
ALICE looks for selected bacteria associated with chronic endometritis.
These tests may identify bacteria that have been linked to infection or inflammation, but they do not directly demonstrate inflammation within the endometrial tissue.
And that distinction matters.
🦠 Bacteria are not necessarily infection.
The presence of bacterial DNA does not automatically establish that:
* The bacteria are causing disease.
* There is an active infection.
* The endometrium is inflamed.
* The bacteria are responsible for miscarriage or implantation failure.
* Antibiotic treatment will improve the chances of a successful pregnancy.
The reproductive tract naturally contains microorganisms, and the significance of many bacterial findings remains uncertain.
Furthermore, detecting bacterial DNA does not necessarily establish that the organisms are alive or actively causing disease.
An abnormal microbiome result is not the same as a histological diagnosis of chronic endometritis.
Similarly, a normal microbiome result cannot reliably exclude endometrial inflammation.
🔍 What is chronic endometritis?
Chronic endometritis is persistent, usually low-grade inflammation of the lining of the womb.
It is different from endometriosis, which is a separate condition.
Chronic endometritis may be associated with recurrent miscarriage, recurrent implantation failure and infertility.
Importantly, many women have no symptoms.
Others may experience irregular bleeding, pelvic discomfort or abnormal discharge.
The characteristic histological finding is the presence of plasma cells within the endometrial tissue.
These can be identified using specialised staining for a marker called CD138.
This allows the pathologist to look for evidence of an inflammatory response within the tissue itself, rather than simply identifying bacteria that may be present.
⚖️ Why does the distinction matter?
Imagine two different endometrial biopsy results.
Patient A — Microbiome testing
Bacteria associated with chronic endometritis are detected.
But does this mean the endometrium is inflamed?
Not necessarily.
The bacteria may be present without causing clinically significant inflammation. Further assessment may be required to determine their relevance.
Patient B — CD138 tissue assessment
Plasma cells are identified within the endometrial tissue.
This provides direct histological evidence supporting chronic endometritis, even if no particular bacterial organism has been identified.
The first result identifies bacteria. The second identifies a tissue response.
They answer different questions.
Neither result, on its own, proves that the finding caused miscarriage or implantation failure.
🧬 Reprognostics Comprehensive Endometrial Biopsy — Looking beyond bacteria
At Innermost Healthcare, we offer the Reprognostics Comprehensive 4-Marker Endometrial Biopsy.
Instead of concentrating on the bacterial environment, this investigation examines four markers within the endometrial tissue.
1️⃣ CD138 — Plasma cells and chronic endometritis
CD138 staining helps identify plasma cells, which are characteristic of chronic endometritis.
Of the four markers, this has the most established role in the histological assessment of chronic endometritis.
An increased plasma-cell population can support the diagnosis and may lead to consideration of treatment, including antibiotics where clinically appropriate.
However, there is no universally agreed diagnostic threshold, and evidence that treatment improves live birth rates remains uncertain.
2️⃣ CD56 — Uterine natural killer cells
Uterine natural killer cells are a normal component of the endometrial immune system.
They have important functions in implantation, placental development and adaptation of the maternal blood vessels.
CD56 staining assesses their presence within the endometrial tissue.
Alterations in uterine NK-cell populations have been investigated in women with recurrent reproductive failure.
However, increased numbers do not necessarily indicate an abnormal immune response, and there is insufficient evidence to recommend immune treatments solely on the basis of CD56 findings.
3️⃣ FoxP3 — Regulatory T cells
Successful pregnancy involves a complex interaction between the embryo and the maternal immune system.
Regulatory T cells contribute to immune tolerance, helping the maternal immune system accommodate the developing pregnancy.
FoxP3 staining provides information about these cells within the endometrium.
This is an important area of reproductive immunology research, although the clinical interpretation of abnormal FoxP3 results is not yet sufficiently established to guide routine treatment.
4️⃣ BCL6 — Endometrial inflammation and possible endometriosis
BCL6 is associated with inflammatory signalling within the endometrium and has been investigated as a marker of possible endometriosis-associated changes.
Some studies have linked increased BCL6 expression with endometriosis, progesterone resistance and implantation failure.
This may be particularly relevant where there are symptoms such as painful periods, pelvic pain, painful in*******se or unexplained unsuccessful embryo transfers.
However, BCL6 cannot independently diagnose endometriosis, and its clinical role remains under investigation.
📚 What does the scientific evidence tell us?
There is an important difference between a test identifying an abnormality and demonstrating that acting on that result improves the chances of having a baby.
Histological examination, particularly CD138 staining, has an established diagnostic role in chronic endometritis.
There is also a growing body of research into endometrial immune cells and inflammatory markers.
However, the evidence supporting all four Reprognostics markers is not equally strong, and the complete panel has not been conclusively demonstrated to improve live birth rates.
The evidence for microbiome-guided treatment is also limited.
In September 2026, the UK Human Fertilisation and Embryology Authority (HFEA) reviewed microbiome testing in fertility treatment.
It concluded that there was insufficient moderate- or high-quality evidence that antibiotic or probiotic treatments following microbiome testing improve the chances of having a baby.
This included patients with recurrent implantation failure and chronic endometritis.
Microbiome testing remains an evolving area of reproductive medicine, but detecting bacterial imbalance alone does not establish that treatment is necessary or beneficial.
🩺 Which investigation may be more useful?
The answer depends on the clinical question.
If we want to identify bacterial species and microbial balance:
EMMA and ALICE provide information about the endometrial microbiome and selected bacteria associated with chronic endometritis.
If we want to examine the endometrial tissue itself:
The Reprognostics Comprehensive 4-Marker Panel evaluates:
✅ CD138 — Plasma cells associated with chronic endometritis
✅ CD56 — Uterine natural killer cells
✅ FoxP3 — Regulatory T cells
✅ BCL6 — An inflammatory marker associated with possible endometriosis
The Reprognostics panel therefore provides a broader assessment of selected tissue and immune markers.
Its principal distinction from microbiome testing is that it can identify a histological inflammatory response through CD138, rather than simply detecting bacteria associated with inflammation.
These investigations are not interchangeable, and neither provides a complete assessment of every potential cause of reproductive failure.
❤️ When might an endometrial biopsy be considered?
A more detailed endometrial assessment may be worth discussing in selected women experiencing:
🔹 Recurrent miscarriage, particularly where standard investigations have not identified a cause.
🔹 Recurrent implantation failure following IVF.
🔹 Suspected chronic endometritis.
🔹 Possible endometriosis, especially where there is pelvic pain or painful periods.
🔹 Unexplained reproductive failure following previous assessment.
Not every woman with recurrent miscarriage or unsuccessful IVF requires an endometrial biopsy.
Assessment should be individualised, taking account of pregnancy history, previous fertility treatment and other recognised causes of reproductive failure.
🌸 Comprehensive Endometrial Biopsy at Innermost Healthcare
At Innermost Healthcare, we offer the Reprognostics Comprehensive 4-Marker Endometrial Biopsy for £799.
All four markers — CD138, CD56, FoxP3 and BCL6 — are assessed as part of one comprehensive investigation.
The biopsy is generally timed for approximately seven days after ovulation, depending on the menstrual cycle and clinical circumstances.
Results are interpreted in conjunction with the patient’s reproductive history, symptoms and previous investigations.
Our aim is to identify potentially relevant findings while recognising that some areas of reproductive immunology remain investigational.
💗 The important message
Finding bacteria is not the same as finding endometritis.
Finding endometritis is not the same as proving it caused a miscarriage.
And identifying an abnormality does not automatically mean that treatment will improve pregnancy outcomes.
The key is understanding what each investigation measures, the strength of the evidence behind it and how the result may genuinely influence clinical management.
For women experiencing recurrent miscarriage or recurrent implantation failure, thoughtful investigation and careful interpretation are more important than simply performing more tests.
Innermost Healthcare
Specialist Women’s Health, Fertility & Reproductive Medicine
🌐 www.innermosthealthcare.com
