Chronic Endometritis: The Hidden Uterine Infection Behind Failed Embryo Transfers

Few things in fertility are as quietly crushing as a failed embryo transfer when everything was supposed to work. The embryo was a good one, perhaps even genetically tested and confirmed to be chromosomally normal. The uterine lining measured exactly as expected, hormone levels were appropriate, and every instruction was followed. Then, after the two-week wait, the pregnancy test comes back negative.

When all the reports appear normal, it can be difficult to understand why implantation failed. In some cases, the reason is not visible on routine fertility tests. Chronic endometritis is a low-grade infection of the uterine lining that often causes no symptoms, cannot be detected on a standard ultrasound, and is not part of every routine IVF evaluation. It is one of the more common hidden causes of recurrent implantation failure and, importantly, one of the few that can often be treated successfully with antibiotics.

This guide is intended for women who have experienced repeated implantation failure with good-quality embryos or multiple early miscarriages despite otherwise normal fertility investigations.

Why Everything Can Look Normal but Implantation Still Fails

Most fertility investigations focus on factors that can be measured. Ultrasounds assess follicle numbers and endometrial thickness, while laboratory evaluation examines embryo quality. When all these factors appear normal, it is easy to assume the uterus is fully prepared for implantation.

Chronic endometritis is different. The uterine lining may appear completely normal on ultrasound while still containing persistent inflammation that only becomes apparent through an endometrial biopsy. As a result, the condition is often discovered only after repeated unsuccessful IVF cycles.

What Is Chronic Endometritis?

Chronic endometritis is a persistent, low-grade infection of the endometrium, the inner lining of the uterus where an embryo implants.

In a healthy uterus, plasma cells are virtually absent from the endometrial lining. These immune cells normally appear when the body is responding to an ongoing infection. Their presence within the endometrium is considered the hallmark of chronic endometritis.

It is important not to confuse chronic endometritis with endometriosis. Although the names sound similar, they are entirely different conditions.

• Chronic endometritis is an infection and inflammation inside the uterine lining.
• Endometriosis involves tissue similar to the uterine lining growing outside the uterus.

The bacteria involved are usually common organisms that naturally live within the body, including E. coli, streptococci, enterococci, Mycoplasma, and Ureaplasma. In most cases, sexually transmitted infections are not responsible. The condition develops when the normal balance of healthy bacteria within the uterus changes.

Why Most Women Don't Notice It

One of the reasons chronic endometritis often remains undiagnosed is that most women experience no symptoms.

When symptoms do occur, they are usually mild and may include:

• Spotting between menstrual periods
• Heavy or prolonged menstrual bleeding
• Mild pelvic discomfort
• Pain during intercourse
• Persistent vaginal discharge

Because these symptoms are non-specific, many women are unaware they have chronic inflammation until fertility investigations identify it.

How Chronic Endometritis Affects Implantation

Successful implantation requires the endometrium to undergo a process called decidualization, where the uterine lining becomes receptive to an embryo during a very short implantation window.

Chronic endometritis interferes with this process in several ways:

• It reduces the production of important implantation proteins such as prolactin and IGFBP-1.
• It weakens the lining's response to progesterone.
• It alters immune cell populations that normally support early pregnancy.
• It may disrupt the subtle uterine contractions that help embryos implant.

Even when a healthy embryo is transferred, an inflamed endometrium may not provide the environment necessary for successful implantation.

Who Should Be Tested?

Routine testing for chronic endometritis is not recommended for every IVF patient. However, it becomes more relevant when implantation repeatedly fails without an obvious explanation.

Your fertility specialist may recommend testing if you have:

• Repeated implantation failure despite transferring good-quality embryos
• Two or more early pregnancy losses
• Findings suggestive of inflammation during hysteroscopy
• Endometriosis
• Endometrial polyps
• Intrauterine adhesions (Asherman's syndrome)

Research has found chronic endometritis in approximately one-third of women with recurrent implantation failure and in an even higher proportion of women experiencing recurrent miscarriage.

How Chronic Endometritis Is Diagnosed

Diagnosis usually involves two complementary procedures.

Hysteroscopy allows the fertility specialist to inspect the uterine cavity directly. Features such as micropolyps, redness, or swelling may suggest inflammation, although many affected women have a normal-looking uterine cavity.

Endometrial biopsy provides the definitive diagnosis. The tissue sample is examined using a special stain called CD138, which highlights plasma cells that would otherwise be difficult to detect under a microscope.

The presence of plasma cells confirms chronic endometritis.

How Is Chronic Endometritis Treated?

Treatment is generally straightforward.

Most women receive a two-week course of doxycycline, taken twice daily. Studies show this successfully clears the infection in the majority of patients.

If inflammation remains on repeat biopsy, an alternative antibiotic regimen may be recommended. Fertility specialists usually confirm the infection has resolved before scheduling a frozen embryo transfer.

Does Treatment Improve IVF Success?

The evidence is encouraging but not definitive.

Several studies have reported improved implantation rates, pregnancy rates, and live birth rates after successful treatment of chronic endometritis in women with recurrent implantation failure or recurrent miscarriage. However, other studies have found less clear benefits, particularly when genetically tested embryos are transferred.

Despite the ongoing debate, testing is often considered worthwhile because:

• The condition is relatively common in women with repeated IVF failure.
• Diagnosis is straightforward.
• Treatment is inexpensive and generally well tolerated.
• It addresses one of the few potentially reversible causes of implantation failure.

When to Speak with a Fertility Specialist

If you have experienced repeated embryo implantation failure or multiple early miscarriages despite otherwise normal fertility investigations, it may be worth discussing chronic endometritis with your fertility specialist.

Identifying and treating hidden inflammation before your next embryo transfer may help eliminate one potential barrier to a successful pregnancy.

If you've had good-quality embryos fail to implant or repeated early pregnancy losses with no clear explanation, book a consultation with MMC IVF to discuss whether further evaluation of your uterine lining may be appropriate.

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