Plasma cell testing – when the uterine lining is chronically inflamed

When embryo transfers repeatedly fail to result in pregnancy or miscarriages recur, our next step is to look for causes that are not visible at first glance. One of these is chronic endometritis (CE) – a silent, often symptom-free inflammation of the uterine lining that is detected through raised plasma cells. Here we explain what this diagnosis means, how the test is carried out and what current science says about it.

What is chronic endometritis?

Chronic endometritis (CE) is a persistent inflammation of the endometrium, the lining of the uterus in which an embryo has to implant. Unlike acute endometritis, which comes with fever, lower abdominal pain and discharge, the chronic form usually causes no noticeable symptoms. Many of those affected do not know that they are affected.

The inflammation is characterised by an infiltration of plasma cells into the uterine lining. Plasma cells are specialised immune cells that produce antibodies; they do not normally occur in a healthy endometrium. Detecting them is therefore a reliable sign of an inflammatory process.

How common is chronic endometritis in fertility patients?

Prevalence varies considerably in the literature: between 10 and 50%, depending on the patient group and the diagnostic criterion used. The range is explained by a lack of standardisation: there is as yet no international consensus on how many plasma cells per field of view are needed for a diagnosis (Kuon & Vomstein, Springermedizin 2024).

For patients undergoing fertility treatment, the literature allows the following reference values to be derived:

• In patients with recurrent implantation failure (RIF), figures vary considerably from study to study, from around 6% to over 40% (Liu et al. 2018)
• In patients with recurrent miscarriage, around 10–12% (Uniklinikum Jena)
• CE occurs significantly more often in infertile women than in fertile women (19.46% vs. 7.7%, p = 0.001; Ticconi et al. 2024)

Important: a recent systematic review (Ticconi et al. 2024) found no significant difference in CE prevalence between RIF patients and fertile controls (6.35% vs. 5.8%, p = 0.9). This means that the association between CE and RIF has not been clearly established in research.

How is the diagnosis made?

Immunohistochemical detection of CD138

The gold standard of CE diagnosis is the detection of CD138-positive plasma cells in an endometrial biopsy by immunohistochemistry (Kuon & Vomstein 2024, Springermedizin).

CD138 (syndecan-1) is a surface molecule that reliably stains plasma cells and makes them distinguishable from other immune cells. A biopsy from the uterine lining is processed histologically and examined for CD138-positive cells.

How is the test carried out?

• Endometrial biopsy (Pipelle biopsy): a thin, flexible catheter is inserted through the cervix and removes a small amount of tissue from the lining. The procedure takes a few minutes, is done on an outpatient basis and is generally well tolerated.
• Immunohistochemical processing: the tissue is sent to the laboratory and examined for CD138-positive plasma cells.
• Evaluation of the findings: the number of plasma cells per field of view is counted (HPF = high-power field). From ≥ 5 CD138-positive plasma cells per HPF, a diagnosis of CE is regarded as confirmed in common practice – although, as described above, there is no international consensus on this threshold.

When do we perform the biopsy?

The biopsy is ideally carried out in the second half of the cycle. In patients without spontaneous cycles, it can be taken in a mock cycle with defined hormone preparation.

What do current study data say about treatment?

Antibiotic treatment for pronounced CE

With a CD138 finding of ≥ 5 plasma cells per HPF, the available data show a treatment effect. A cohort study of 640 women (Xiong et al., Fertility & Sterility 2021) examined the influence of oral antibiotic treatment on pregnancy rates in frozen embryo transfer:

• The cure rate after antibiotic therapy was 89% (with CD138 ≥ 5/HPF)
• After successful treatment (CD138 ≤ 4/HPF), the implantation rate (51.6% vs. 32.3%), clinical pregnancy rate (65.7% vs. 42.3%) and live birth rate (52.1% vs. 30.7%) were significantly higher than with persistent CE

Mild CE: the evidence is less clear

With a mild finding (1–4 plasma cells/HPF), the data are more complex. A recent study of 681 patients with mild CE (Xu et al., Fertility & Sterility 2025) found no significant difference in the live birth rate between treated and untreated women (47.5% vs. 51.8%, RR 0.92, 95% CI 0.78–1.08). Diagnosis and therapeutic approach in mild findings therefore remain a clinical decision made case by case.

A special case: endometriosis

A study from the Medical University of Vienna (Hager et al., Sci Rep 2026) examined 92 infertile women with CE. In patients who also had endometriosis, the risk of persistent CE after antibiotics was significantly increased (OR 2.893, p = 0.026), as it was with adenomyosis (OR 10.277, p < 0.001). In the multivariable analysis, however, only adenomyosis remained independently significant. This means that above all with adenomyosis, but also with endometriosis, a second follow-up biopsy after treatment can be useful.

Which antibiotics are used?

The substance used most often in the literature is Doxycyclin (100 mg twice daily for 14 days). Alternatively or in combination, Levofloxacin and Metronidazol are used. The specific treatment decision is made by your doctor on the basis of the findings and your individual situation.

After treatment we generally recommend a follow-up biopsy to confirm that the therapy has worked, especially with a pronounced initial finding or co-existing endometriosis.

For whom does plasma cell testing make sense?

We recommend the test in cases of:

• Recurrent implantation failure (at least 3 unsuccessful embryo transfers despite good embryo quality)
• Recurrent miscarriage (≥ 2 miscarriages)
• Unexplained infertility with no other finding

The test is not a routine step at the start of fertility treatment; it is used specifically in patients in whom other causes have already been ruled out or in whom there is a clinical suspicion.

What does the test cost?

• Biopsy (medical service): approx. €100
• Laboratory test (statutory health insurance patients): currently covered by statutory health insurance
• Laboratory test (private insurance / self-pay): approx. €160

If CE is detected and antibiotic therapy follows, there are additional costs for the follow-up biopsy and the medication. We will be happy to advise you in a consultation on the costs that apply to you.

What we want to tell you honestly

Plasma cell testing is a useful tool, but not a cure-all. The research picture is nuanced: with pronounced CE and successful treatment, studies show improved pregnancy rates. With mild CE, the benefit of antibiotic treatment is not clearly established on current knowledge.

What we can promise you: we evaluate the findings carefully and explain what they mean and what they do not mean. We decide together with you whether and how to proceed. No unnecessary procedure, no overtreatment – but also no looking away when there is a finding that can be treated.

Dr. med. Susann Kreuz is managing physician at Praxis für Fertilität – Kinderwunsch- und EndometrioseZentrum Berlin.

Sources

• Ticconi C et al. (2024): Chronic endometritis and recurrent reproductive failure: a systematic review and meta-analysis. Front Immunol 15:1427454
• Xiong Y et al. (2021): Impact of oral antibiotic treatment for chronic endometritis on pregnancy outcomes. Fertil Steril 116(2):413–421
• Kuon RJ & Vomstein K (2024): Springermedizin – Bedeutung der chronischen Endometritis bei RIF und wiederholten Fehlgeburten
• Hager M, Ott J, Holzer I, Walch K, Marschalek J et al. (2026): A retrospective analysis of chronic endometritis and antibiotic therapy in patients with endometriosis. Sci Rep. DOI: 10.1038/s41598-026-48809-4
• Xu Y et al. (2025): The effect of antibiotic treatment on pregnancy outcomes in patients with mild chronic endometritis undergoing IVF. Fertil Steril 124(4):711–719
• Uniklinikum Jena – Plasmazellen CD138+: Patienteninformation
• Liu Y, Chen X, Huang J, Wang CC, Yu MY, Laird S, Li TC (2018): Comparison of the prevalence of chronic endometritis as determined by means of different diagnostic methods in women with and without reproductive failure. Fertil Steril 109(5):832–839