Endometriosis. How does chronic endometriosis affect embryo implantation?

What is endometritis and why is it dangerous?

Endometritis is an inflammation of the uterine lining (endometrium) that can manifest in either an acute or chronic form. Endometritis poses a serious threat to women's reproductive health: it can lead to infertility, miscarriage, the formation of intrauterine adhesions, and in severe cases, the spread of infection to the pelvic organs and the development of sepsis.

Acute and chronic endometritis: what is the difference?

Acute endometritis is a rare urgent condition that usually develops in the context of a delay in the expulsion of placental fragments (postpartum endometritis), a miscarriage, or a sexually transmitted pathogen. It manifests with a series of typical infection symptoms (increased temperature, purulent discharge, pronounced lower abdominal pain, general discomfort). In the absence of prompt treatment, the infection can spread.

Chronic endometritis is a persistent inflammation of the endometrial lining caused by an infection of the uterine cavity, primarily by bacterial pathogens. It usually progresses without symptoms or presents nonspecific symptoms such as uterine bleeding (vaginal discharge in cases of endometritis, occurring mid-cycle or before/after menstruation), periodic lower abdominal pain, or foul-smelling vaginal discharge.

Causes of endometrial inflammation

The most common causes of endometritis are ascending infections related to childbirth, abortions, intrauterine procedures, or sexually transmitted infections. These conditions disrupt natural barriers and facilitate the entry of pathogenic microorganisms into the uterine cavity. The pathogens responsible for endometritis include conditionally pathogenic bacteria and sexually transmitted infections: Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma, and Ureaplasma.

Chronic endometritis and reproductive health

Chronic endometritis (CE) is often asymptomatic or presents few symptoms, but it has a significant impact on a woman's reproductive function.

Effects on reproductive health:

Implantation disorders: prolonged and chronic inflammation of the uterine lining alters the structure and receptor profile of the endometrium, thereby affecting its ability to accommodate an embryo.

Infertility: chronic inflammation can be the sole cause of inability to conceive.

Miscarriages — chronic endometritis is associated with an increased risk of spontaneous miscarriages and non-viable pregnancies.

IVF failures — the rate of implantation failures is significantly higher in cases of chronic endometritis, and treating the inflammation increases the chances of success in assisted reproductive techniques.

Formation of intrauterine adhesions: in advanced cases, inflammation can lead to synechiae (adhesions), which reduces fertility (Asherman's syndrome).

Chronic endometritis is an important factor to consider when examining women with reproductive disorders.

Why does chronic endometritis prevent embryo implantation?

Chronic endometritis is diagnosed in 10% of women of childbearing age, but this rate is significantly higher in women with repeated embryo implantation failures (repeated implantation failures or RIF) and in women with recurrent miscarriages (RPL) (10-66%).

Often, both acute and chronic endometritis lead to the formation of adhesions in the endometrium, called synechiae, which disrupt the implantation process and early development of the embryo. One of the important consequences of endometritis is also a disruption, insufficient growth of the endometrium (endometrial hypoplasia), or irregular growth of the endometrium (focal hyperplasia, polyps). In our blog, we have addressed the issue of IVF in cases of endometrial hyperplasia.

The presence of inflammation in the uterine cavity can disrupt the balance of immune system cells in the endometrium, which can affect receptivity to the embryo, hinder implantation, and proper embryo development. (Bashiri et al. 2018).

Diagnosis of chronic endometritis

The diagnosis of chronic endometritis is a complex task, as the disease often progresses without symptoms or with nonspecific clinical manifestations. Reliable detection of an inflammatory process in the uterine lining requires a comprehensive approach that includes clinical evaluation, instrumental methods, and laboratory examinations.

The diagnosis is particularly important in reproductive medicine, where chronic inflammation of the endometrium can be a key factor in infertility and implantation failures.

Hysteroscopy, pipelle biopsy, IGH, PCR and other methods

The diagnosis of chronic endometritis is made using ultrasound, endometrial biopsy by Cornier pipelle, or during hysteroscopy.

During a pelvic ultrasound, signs of exacerbation of chronic endometritis are often observed in the form of an irregular structure of the endometrium.

The diagnosis is confirmed by histological examination and immunohistochemistry (presence of CD 138) — plasma cells — specific immune system cells that react to inflammation. It is known that the presence of microorganisms producing inflammation and the immune system reaction that develops in response can reduce the receptivity (sensitivity) of the endometrium.

During hysteroscopy, endometritis often manifests as micro polyps, areas of redness, and irregular growth.

Laboratory diagnosis of endometritis:

• complete blood count;
• determination of C-reactive protein;
• microscopy and culture of swabs.

PCR analysis can be used to detect infectious agents associated with the development of endometritis, especially in cases of chronic inflammation.

When and who should undergo examination

An examination for endometritis is recommended in the following cases:

Women with reproductive function disorders — in cases of unexplained infertility, repeated IVF failures, recurrent miscarriages.

After childbirth, abortion, or intrauterine procedure, in cases of pain, discharge, or low-grade fever.

In the presence of chronic inflammatory diseases of the pelvic organs, particularly associated with menstrual cycle disorders, pain, or discharge.

In women with prolonged intermenstrual bleeding or lower abdominal pain.

In cases of suspected adhesions in the uterine cavity (e.g., as a result of ultrasound or hysteroscopy).

The examination is particularly important before planning a pregnancy, including when preparing for IVF (in vitro fertilization).

Treatment of chronic endometritis before planning a pregnancy

It has been established that chronic inflammation of the endometrium triggers an immune system response and thus affects the endometrium's ability to undergo the necessary changes for implantation (it disrupts receptor sensitivity to sex hormones and embryo receptivity).

After treating chronic endometritis, the prognosis for a successful pregnancy improves.

It is recommended to treat endometritis for 14 days with antibiotics, with efficacy exceeding 90% of cases after the first treatment cycle.

Outcome control is performed three weeks after the end of antibiotic treatment through endometrial biopsy.

Bibliography

Kimura et al. (2019). Unraveling Chronic Endometritis: A Review Journal of Obstetrics and Gynaecology Research, 45(5), p. 1397–1408.

Ticconi, Inversetti et al. Chronic Endometritis and Recurrent Reproductive Failure: A Systematic Review and Meta‑Analysis. Frontiers in Immunology, 15, Article 1427454 (2024).