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Chronic inflammation (chronic endometritis) | Its role in implantation failure and miscarriage

Before we can understand chronic inflammation and its important role in reproduction, we must first understand what inflammation is.

What is inflammation?

Inflammation is the body’s attempt to protect itself against infections, irritants and damaged cells. Inflammation is part of the body’s immune response. Initially, inflammation is beneficial. For example, when your body is trying to fight off an infection from bacteria. However, sometimes inflammation can cause further inflammation; it can become self-perpetuating even after the initial cause is gone. In this situation, inflammation can be harmful.

Acute versus chronic inflammation

Acute inflammation starts rapidly and quickly becomes severe. Signs and symptoms are only present for a few days, but in some cases may persist for longer. There are 5 main signs and symptoms of acute inflammation:

  • Pain – Chemicals that stimulate nerve endings are released which causes pain.
  • Redness – Increased blood flow to the affected area causes the red appearance
  • Warmth – Increased blood flow to the affected area also results in warmth locally
  • Swelling – caused by the leakage of fluid from the local blood vessels
  • Immobility – this mostly applies to inflammation in joints

Acute inflammation is generally easily to recognize and treat.

Chronic inflammation means long-term inflammation, which can last for several months and even years. It can result from the failure to eliminate whatever was causing an acute inflammation (persistent bacteria), a chronic irritant of low intensity that persists or when the immune system attacks healthy tissue mistaking it for harmful pathogens.

Chronic inflammation may be difficult to diagnose and effective treatment is often unknown.

Chronic Inflammation of the uterine lining

Inflammation is an increasingly recognized factor contributing to reproductive dysfunction, including several common causes of infertility such as pelvic inflammatory disease, polycystic ovary syndrome, obesity, endometriosis, and recurrent pregnancy loss. Recently, chronic inflammation affecting the uterine lining has been of special interest. This is called chronic endometritis.

What problems does chronic inflammation of the uterus cause?

The uterine lining is responsible for developing the ability to allow an embryo to implant. Estrogen and progesterone production from the ovaries induce the changes in the uterine lining that are necessary for implantation. The changes that occur in the uterine lining are extremely complex and not well understood. Some studies have identified chronic inflammation in women with implantation failure. It is also believed that inflammation in the uterine lining may increase the risk for a miscarriage.

How can chronic inflammation of the uterus be diagnosed?

Blood tests for chronic inflammation

There are some blood tests which are general, non-specific markers of inflammation. One marker is called the erythrocyte sedimentation rate (also known as ESR or “sed rate”). The sed rate is not very useful when studying reproductive age females because it is affected by estrogen levels. Another marker is called C Reactive Protein or CRP. CRP is not affected by hormone levels so is a much more liable indicator of inflammation in women. Very high levels of CRP (>10) are usually an indicator of an acute infection. Moderately elevated levels can be an indicator of low grade chronic inflammation.

Examination of the uterine lining

The uterine lining can be visualized directly by inserting a fiber optic telescope into the uterine cavity. This is called hysteroscopy. Sometimes, chronic endometritis can be diagnosed be diagnosed by this method. For example, the presence of micropolyps is a reliable indicator of chronic endometritis. These are abnormalities that will not show up on other types of imaging such as an HSG or HSN.

micropolyps

Hysteroscopy can also be used to obtain a sample or biopsy of the uterine lining that can be viewed under a microscope. In the uterine lining, one of the types of white blood cells which is a hallmark of chronic inflammation are the “plasma” cells. Plasma cells can be seen by looking at a piece of the uterine lining under a microscope. However, due to the presence of other similar looking cells, it is not always easy to determine the presence of an abnormal amount of plasma cells. Plasma cells have a marker on their surface which is called CD138. It is possible to stain a sample of endometrial tissue so that the CD138 stands out. This is a more reliable method to diagnose chronic endometritis.

Diagnosing chronic endometritis

Left side standard microscopic image of chronic endometritis. It is difficult to identify the plasma cells. Right side – after staining with CD138. The arrows show the plasma cells.

How can you treat chronic inflammation?

If a specific cause for the inflammation can be identified then treatment of the cause should cause resolution of the accompanying inflammation. For example, if a bacterial infection is found, treatment with antibiotics can be tried.

Recently, a study found an increase in the pregnancy and live birth rates when women with mildly elevated CRP levels were treated before they got pregnant with low dose aspirin. The improvement was not seen in obese women, however.

In study in bovines also found that exposure to platelet rich plasma (PRP) would suppress the production of some of the proteins produced in the uterine lining as a result of inflammation.