Description
What is the Comprehensive Endometrial Biopsy – 4 Marker Panel?
This test involves taking a small sample of the lining of the womb, known as the endometrium, using a fine endometrial sampling device.
The sample is sent to the specialist Reprognostics laboratory in Mannheim, Germany for histological and immunohistochemical analysis.
Rather than assessing a single marker in isolation, the panel evaluates four different endometrial markers:
- CD56-positive uterine natural killer (uNK) cells
- CD138-positive plasma cells
- FoxP3-positive regulatory T cells (Tregs)
- BCL6 expression (HSCORE)
These markers examine different aspects of the endometrial immune and inflammatory environment.
Who might consider this test?
Endometrial immune and inflammatory testing may be considered in selected patients with:
- recurrent miscarriage
- recurrent implantation failure
- unexplained infertility
- suspected chronic endometritis
- concerns about endometrial inflammation or immune function
This type of testing is not a replacement for standard recurrent miscarriage or fertility investigations.
You can read more about our overall approach in our Understanding Recurrent Miscarriage guide:
https://innermosthealthcare.com/understanding-recurrent-miscarriage/
If you are unsure whether this test is appropriate, a Specialist Miscarriage Consultation can be used to review your pregnancy history, previous investigations and whether further testing is justified:
https://innermosthealthcare.com/product/consultation-miscarriage/
Why assess four markers?
Different endometrial biopsy services assess different biological markers.
Some tests assess only one marker, such as uterine natural killer cells. The Reprognostics panel assesses four complementary markers from a single biopsy.
Because these markers relate to different proposed biological mechanisms, it can be difficult to justify selecting one marker while excluding the others before the biopsy has been performed.
The four-marker approach therefore provides a broader assessment of the endometrial environment from one sample.
What does the biopsy involve?
The biopsy is performed through the vagina and cervix using a fine endometrial sampling device.
The procedure usually takes only a few minutes.
Some patients experience period-like discomfort or cramping during the procedure. Light vaginal bleeding or spotting can occur afterwards and may continue for one or two days.
Simple pain relief such as paracetamol can usually be taken if required.
We generally advise avoiding unprotected sexual intercourse during the biopsy cycle.
When is the biopsy performed?
Correct timing is important because the endometrium changes throughout the menstrual cycle.
The biopsy is usually performed during the mid-luteal phase, approximately:
- 7–10 days after ovulation in a natural cycle, or
- 7–10 days after starting progesterone in an appropriately managed hormone replacement cycle.
For patients with regular cycles, we may provisionally arrange the biopsy around cycle day 21–23, depending on cycle length.
Ovulation prediction tests may be used to identify the LH surge so that the biopsy can be timed appropriately.
We will advise you on the timing of your individual test.
What markers are analysed?
CD56-positive uterine natural killer cells
Uterine natural killer cells are a normal component of the endometrium and have roles in implantation, placentation and early pregnancy.
The biopsy assesses the number and distribution of CD56-positive uNK cells within the endometrial tissue.
Altered uNK-cell findings have been reported in some patients with recurrent miscarriage or implantation failure, although their clinical significance remains uncertain.
CD138-positive plasma cells
Plasma cells within the endometrium can be identified using CD138 immunohistochemistry.
Increased numbers of CD138-positive plasma cells may support the histological assessment of chronic endometritis, which has been associated in some studies with infertility, implantation failure and recurrent pregnancy loss.
The result must be interpreted alongside the clinical history and other findings.
FoxP3-positive regulatory T cells
Regulatory T cells, or Tregs, are involved in immune regulation and tolerance.
FoxP3 is used as a marker for regulatory T cells within the endometrium.
Altered Treg numbers or distribution have been investigated in relation to implantation and recurrent pregnancy loss, although the clinical implications remain an area of continuing research.
BCL6 expression
BCL6 is an inflammatory-associated marker that can be measured within the endometrium.
Increased endometrial BCL6 expression has been associated in some studies with endometriosis and implantation dysfunction.
BCL6 testing should not, however, be regarded as a standalone diagnostic test for endometriosis.
How are the results reported?
The laboratory provides a specialist report describing the findings for each of the four markers.
The results are reviewed in the context of your:
- fertility or pregnancy history
- previous investigations
- clinical symptoms
- ultrasound findings
- treatment history
An abnormal result does not necessarily mean that the finding is the cause of miscarriage or infertility.
Laboratory analysis
Samples are sent by medical courier to:
Reprognostics
Mannheim, Germany
Reprognostics specialises in endometrial and reproductive immunology testing.
The laboratory assesses the biopsy using histological and immunohistochemical techniques to evaluate the four-marker panel.
More information about Reprognostics is available here:
Evidence and limitations
Endometrial immune and implantation testing remains an evolving area of reproductive medicine.
Associations have been reported between some endometrial immune or inflammatory markers and recurrent miscarriage, implantation failure or infertility, but the evidence that testing or treating these abnormalities improves the chance of a successful pregnancy remains limited.
In particular:
- uterine natural killer cells are a normal component of the endometrium
- there is no universally agreed definition of an abnormal uNK-cell result
- BCL6 is not a diagnostic test for endometriosis
- CD138-positive plasma cells may support the diagnosis of chronic endometritis, but interpretation varies between laboratories and studies
- the clinical significance of altered regulatory T cells remains uncertain
For this reason, these investigations should be considered specialist or adjunctive tests, rather than routine first-line fertility or recurrent miscarriage investigations.
The University of Warwick/UHCW Implantation Research Clinic also investigates endometrial function and uterine natural killer cells and explicitly describes these as research tests:
https://warwick.ac.uk/fac/sci/med/research/biomedical/tem/clinic/
This is useful independent context because it reflects the continuing research status of endometrial immune and implantation testing.
Other endometrial biopsy options
We also offer a separate histology-only endometrial biopsy where immune-marker testing is not required.
This is a different service from the comprehensive four-marker Reprognostics panel and should not be regarded as an equivalent test at a lower price.
Price
The price includes:
- endometrial biopsy procedure
- sampling equipment
- four-marker specialist laboratory analysis
- international medical courier transport to Germany
- review and interpretation of the laboratory report
Book an endometrial biopsy in Cardiff
The Comprehensive Endometrial Biopsy – 4 Marker Panel is available at Innermost Healthcare in Cardiff.
If you are considering endometrial testing because of recurrent miscarriage, recurrent implantation failure or unexplained infertility, we recommend discussing whether the test is appropriate for your individual circumstances before booking.
For broader information about our miscarriage services:
https://innermosthealthcare.com/miscarriage/
For a consultant-led review before testing:
https://innermosthealthcare.com/product/consultation-miscarriage/
