IVF experts like me are learning what factors might result in IVF failure.
A successful IVF cycle requires a healthy, normal embryo and a healthy normal uterus.
Chronic endometritis, which is the presence of inflammation in the uterine lining,
is one factor that causes IVF failure. Stay tuned and I will explain.
Patients with chronic endometritis do not have any symptoms. They do not have
any differences in their periods or have pain or discharge. How, then, is endometritis diagnosed?
The uterine cavity is lined with cells which collectively are referred to the endometrium.
Abnormalities in the uterine cavity such as scar tissue, polyps and fibroids can result in IVF
failure. These abnormalities can be detected by looking inside the uterus with a hysteroscope or
by performing the X-ray test known as an HSG or by performing a saline ultrasound.
Inflammation of the uterine lining, however, is harder to detect. It cannot be detected
with an HSG or saline ultrasound. Using hysteroscopy, some patients with chronic
endometritis might be found to have redness or tiny growths known as micropolyps.
The most accurate way to diagnose chronic endometritis, however, is by taking a sample
of the uterine lining, known as an endometrial biopsy, and looking at it under the microscope.
Even under the microscope it can still be tricky to determine if a patient has endometritis.
The hallmark for endometritis is finding a type of white blood cells known as
plasma cells. Plasma cells can be tough to pick out under the microscope. Can you see
the plasma cells in this specimen? I can’t. The best way is to look at the endometrium using a
special type of microscopic staining procedure known as a CD138 stain.
This highlights the plasma cells and makes it easy for anybody to see.
Many women with a healthy uterus
may have a small number of plasma cells. The patients that we say have chronic
endometritis have a larger number of plasma cells visible under the microscope like this.
What causes endometritis?
Like the vagina, the inside of the uterine cavity contains bacteria. We
can divide the bacteria into two types: good and bad. Good bacteria don’t cause
any problems with a woman’s reproductive ability. Bad bacteria are those that cause
the patient’s body to produce those plasma cells. Remember, plasma cells are white
blood cells. White blood cells are what the body uses to fight off bad bacteria.
How does endometritis cause IVF failure? It isn’t really known how chronic
endometritis causes IVF failure. It may be that the bacteria themselves are to blame.
It might also be chemicals that the plasma cells produce to get rid of the bad bacteria.
Or some combination of both. At this point, we don’t really know
How is chronic endometritis treated? Antibiotics are currently the treatment
used to try to get rid of chronic endometritis. The first antibiotic that is used to treat
endometritis is called doxycycline. Doxycycline treats a wide variety of bacteria and is easy to
get and is inexpensive. The treatment course is usually twice a day for two weeks. Studies show
that chronic endometritis can be eradicated with doxycycline about 75% of the time. The way doctors
determine if the treatment was successful is by repeating a second endometrial biopsy. If
there are only a small number of plasma cells remaining or none, then the patient can proceed
with an embryo transfer. If the number of plasma cells is still high, then the patient will get
a second course of treatment with some different antibiotics. About 75% of the patients who weren’t
cured after the first course of doxycycline will be cured after the second course. This means
that a small number of patients, about 10% will have persistent chronic endometritis.
It might be that these patients have bacteria that are resistant to antibiotics
or some other cause like viruses or even a problem with the immune system. We don’t really know.
Is treatment of chronic endometritis effective at reducing IVF failure?
Yes. There are a number of studies that have shown that this kind of treatment can reduce IVF failure
rates. For example, this study was published in 2021. Investigators did endometrial biopsies after
couples had failed 2 or 3 failed embryo transfers. They divided the patients into three groups.
Group 1 were patients who did not have chronic endometritis. Group 2 were patients who had
a small number of plasma cells without having received antibiotics. Group three were patients
who had a small number of plasma cells after receiving antibiotic treatment. There was no
difference in these three groups in the percentage of patients who became pregnant or delivered.
Next they compared patients who had their chronic endometritis cured with antibiotics
and those who were not cured, in other words, those with persistent chronic endometritis.
They found that those patient with persistent chronic endometritis
had lower pregnancy rates and lower live birth rates
Our InfertilityTV bottom line is this. Chronic endometritis is one cause for IVF failure.
Patients undergoing IVF should have an endometrial biopsy to look for chronic endometritis and treat
it if it is found. Patients with persistent endometritis should be counseled that they may
have a lower chance for pregnancy but that it is still reasonable to attempt embryo transfer