https://doi.org/10.53453/ms.2023.6.20
Literature review: deep endometriosis diagnostic and treatment
challenges
Dominyka Grinciūtė
1
, Ernestas Frolovas
2
1
Vilnius University, Faculty of Medicine, Vilnius, Lithuania.
2
Vilnius University Hospital Santaros klinikos, Department of Obstetrics and Gynecology, Vilnius, Lithuania
Abstract
Background and aim. Deep endometriosis (DE) is defined as endometriotic lesions that extend more than 5 mm
below the surface of the peritoneum. Women of reproductive age with this disease experience pain, infertility, and a
consequent decline in quality of life. Deep endometriosis' exact mechanics and pathophysiology remain poorly known,
which makes diagnosis and treatment challenging.
Materials and Methods. We searched PubMed and Google Scholar databases to compare the diagnostic value of
non-invasive procedures like transvaginal ultrasound and magnetic resonance imaging with diagnostic laparoscopy
with tissue biopsy. We also used the same databases to research the best deep endometriosis treatment strategy.
Results. The quality of non-invasive diagnosis highly depends on the deep endometriosis location. #Enzian
classification is a valuable tool in improving the sensitivity and specificity of TVUS. The treatment options differ
throughout different guidelines; however, they all agree that treatment should be individualized depending on the
patient's age and complaints.
Conclusion. Non-invasive diagnostic techniques can safely replace diagnostic laparoscopy; however, their site-
specificity and the need for a trained professional should be kept in mind. Conservative therapy should be the first line
for pain management, and assisted reproductive techniques should be used for infertility treatment. Surgery should
only be considered when both of these options are exhausted.
Keywords: deep endometriosis, non-surgical diagnosis, treatment, pain, infertility.
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Medical Sciences 2023 Vol. 11 (5), p. 168-174, https://doi.org/10.53453/ms.2023.6.20
168
1. Introduction
Rokitansky was the first to describe deep
endometriosis disease. Later, T. Cullen described it as
adenomyosis of the round ligament. As new
discoveries were made over time, the definitions
evolved. DE, formerly known as deep infiltrative
endometriosis, is now most commonly defined as
endometriotic lesions that extend more than 5 mm
below the surface of the peritoneum (1). Deep
endometriosis' pathophysiology is not entirely
understood, just like it is for the other types of
endometriosis (2). DE symptoms vary based on the
location and do not correlate with the severity of the
condition. It tends to affect rectovaginal fascia,
rectum, uterosacral ligaments, small bowel, omentum,
urinary tract, and vagina (3). Estimating the
prevalence of DE is challenging because a definitive
diagnosis can only be acquired after diagnostic
laparoscopy with tissue biopsy. DE affects fertile-age
women and results in pain, infertility, and a lower
quality of life, continuing to be a significant medical
issue (4). The Enzian classification was the main
classification used for deep endometriosis; however, it
does not evaluate peritoneal and ovarian
endometriosis and adhesions. Therefore, the #Enzian
classification was developed to estimate all forms of
endometriosis, enabling assessment of the full scope
of the disease (5,6). This review will discuss some
diagnostic and therapeutic challenges arising from the
lack of knowledge about deep endometriosis.
2. Materials and methods
To evaluate whether non-invasive procedures like
transvaginal ultrasound or magnetic resonance
imaging can take the role of diagnostic laparoscopy
with tissue biopsy, we performed a search using
PubMed and Google Scholar databases. In addition,
the same databases were used to search for the best
treatment strategy for DE.
3. Discussion
3.1. Diagnosis
Transvaginal ultrasound (TVUS) and magnetic
resonance imaging (MRI)
Discussing diagnosis, the primary question is which
diagnostic method is the most accurate and whether
invasive diagnostic laparoscopy can be avoided.
Clinical examination should proceed as with other
endometriosis forms, focusing on symptoms such as
dysmenorrhea, dyspareunia, dyschezia, dysuria,
chronic pelvic pain, and infertility, also evaluating
previous medical history along with the family history
of possible endometriosis. However, endometriosis
may be asymptomatic, making a diagnosis based
solely on anamnesis and symptoms insufficient (7–9).
Therefore, the next step should be a clinical
examination, which includes checking the posterior
vaginal fornix with a speculum for dark nodules and
retraction, as well as performing a digital exam to
assess the uterus' mobility and consistency and check
for any potential bladder, uterosacral ligament,
rectovaginal fascia and the pouch of Douglas
invasions. Finally, digital examination per rectum can
reveal rectal involvement. However, it can be painful,
and the authors disagree on the sensitivity and
specificity of clinical examination. (7,10).
Usually, TVUS does not require any preparation;
however, some studies have indicated that bowel
preparation can improve TVUS results because it
clears gas and feces from the rectosigmoid colon,
which enhances the image of the pelvic cavity and
removes artifacts (11,12). Another method for
improving imaging of the vagina and rectovaginal
septum during TVUS is to add some couplant to the
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probe condom since the air space between the vagina
and the probe can create artifacts (13). To assess the
anterior compartment and uterus effectively, patients
should empty the bladder and drink a glass of water
just before the procedure (11). The International Deep
Endometriosis Analysis (IDEA) group proposed a
four-step TVUS assessment algorithm. A routine
examination of the uterus and adnexa for adenomyosis
and endometriomas is the first step. In the second step,
"soft markers" are evaluated. The third step evaluates
Dougla's pouch based on the 'sliding-sign'. The last
step is the assessment of deep endometriosis nodules
in anterior and posterior compartments. Instead of
random inspection, this technique enables
sonographers to do so in a systematic manner for
greater accuracy. (10). TVUS sensitivity and
specificity were evaluated by S. Yin et al. based on the
site of deep endometriosis. When diagnosing
uterosacral ligament endometriosis, TVUS had the
maximum sensitivity (96,75%). Sensitivity and
specificity of 73,68% and 94,33%, respectively, for
rectovaginal septum, also suggest significant
diagnostic value. The broad ligament's deep
endometriosis had the lowest detection sensitivity
(10%). However, this site's specificity was 100%.
Intestinal endometriosis had the highest correlation
between TVUS and surgical findings; TVUS
sensitivity and specificity were 94,94 % and 94,96 %,
respectively. TVUS sensitivity of other deep
endometriosis sites ranges from 73,68 % to 50 %, and
specificity ranges from 100 % to 94,33 %. We can
conclude from this study that while the diagnostic
value of ultrasonography depends on the site, DE of
the uterosacral ligaments, intestine, and rectovaginal
septum has the highest diagnostic value (13). Using
the #Enzian classification, E. Montanari et al. carried
out a prospective multicenter study on the diagnostic
accuracy of sonography for the non-invasive diagnosis
of ovarian and deep endometriosis. Researchers
concluded that endometriotic lesions could be
accurately and non-invasively detected with TVUS
because there was an 86% to 99% correlation between
TVUS and surgical findings, depending on the
#Enzian compartments under examination. (14). The
final point we want to emphasize is its low cost and
emphasis on rectovaginal endometriosis and
uterosacral ligaments; yet, it is skill- and experience-
dependent. (11,13).
Deep endometriosis can be detected by magnetic
resonance imaging (MRI) as "implants or tissue
masses that present as hypointense areas and/or
hyperintense foci on T1- or T2-weighted images in the
following locations: the torus uterinus, uterosacral
ligaments, vagina, rectovaginal septum, rectosigmoid,
pouch of Douglas, parametrium, bladder, and round
ligaments" (7). MRI is usually performed as a second-
line investigation which should be performed using
ether1, 5-T, or 3-T magnets. Preparation for MRI
requires 4 hours of fasting before the examination to
avoid vomiting. The same method described for
TVUS, bladder preparation may be employed because
the bladder should be fairly filled. However, there is
no consensus among authors on whether bowel
preparation improves accuracy (7,15,16).
In a meta-analysis, V. Nisenblat et al. compared TVUS
and MRI to diagnostic laparoscopy. TVUS's
sensitivity and specificity for detecting deep
endometriosis were 79 % and 94 %, respectively,
which approached the criteria for SpPin triage test.
The sensitivity and specificity of the MRI were 94 %
and 77 %, respectively, reaching the standards for a
replacement test and a SnNout triage test (table 1).
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According to the available information, TVUS has a
higher diagnostic value as a non-invasive technology
than MRI and can be utilized for preoperative planning
more effectively (17). P. V. Foti et al. disagree with
this study and contend that the best method for
preoperative staging of endometriosis is magnetic
resonance imaging. Yet to reach this result, this study
also considered ovarian and peritoneal endometriosis.
It also gives sensitivity and specificity depending on
deep endometriosis locations (18). As V. Nisenblat et
al. meta-analysis does not evaluate MRI sensitivity
and specificity in relation to particular sites, it is
difficult to compare these two investigations fairly. S.
Guerriero et al. systematic review and meta-analysis
assessed the sensitivity and specificity of TVUS and
MRI of specific sites such as the rectosigmoid,
rectovaginal septum, and uterosacral ligaments. TVUS
and MRI performed similarly in terms of diagnostic
power, with the maximum sensitivity only reaching
70 % and specificities for all sites ranging from 86 %
to 97 %. The least sensitive diagnostic methods for
detecting endometriosis of the rectovaginal septum
were TVUS and MRI, with sensitivity values of 59 %
and 66 %, respectively. Both techniques showed the
highest and equal specificity for rectosigmoid
endometriosis at 85 % (19).
Having discussed TVUS and MRI, we believe that
TVUS can replace diagnostic laparoscopy and should
be prioritized, considering the cost. According to
patient complaints, MRI may be employed as a
second-line diagnostic method for sites with reduced
TVUS sensitivity. Yet, because studies have produced
varying outcomes and were conducted in various
ways, we are unable to determine which diagnostic
technique is better.
3.2. Treatment
3.2.1. Pharmaceutical therapy
Medical therapy should be the first choice in treating
deep endometriosis as the disease can affect the whole
bowel, and the excision of deep lesions may lead to
major and minor complications (20,21). Progestins are
recommended as the first-line treatment for women
with endometriosis in all six national and two
international guidelines that D.R. Kalaitzopoulos et al.
reviewed (21). The primary choice for progestins
should be Dienogest as it has shown significant pain
relief; however, it has practically no effect on reducing
the size of endometriotic implants (21–23). Combined
oral contraceptive pills should be the first choice for
empirical treatment for patients who do not wish to
conceive (21)). NSAIDs can also be used as first-line
treatment for pain management; however, long-term
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use can cause side effects, and a Cochrane review
showed no effect compared to placebo (21,24).
Gonadotropin-releasing hormone agonists/antagonists
and aromatase inhibitors are the second-line
treatments. They should only be used if the first-line
treatment fails as they have more side effects, and
aromatase inhibitors should not be used as
monotherapy but in combination with first- or second-
line drugs (21). Conservative treatment has shown to
be helpful in stopping the lesions' growth and inducing
their regression. However, when a medication is
stopped, the problems frequently return (21,25).
3.2.2. Pain and infertility
As previously stated, medical therapy should be the
first line of treatment for women whose primary
complaint is pain. The patient should continue medical
therapy if the disease is stable after the follow-up.
However, surgery should be considered if
pharmaceutical treatment fails and the pain persists or
worsens, or pain during the time of endometriosis
diagnosis was seven or more according to the visual
analog scale (VAS). If a woman experiences pain and
infertility, the Anti-Mullerian hormone (AMH) and
the patient's age should be evaluated. The initial option
should be surgery followed by in vitro fertilization
(IVF) if AMH is normal and the age is 30 years or less.
Surgery should be performed after gamete
cryopreservation if AMH is low and the patient is
older than 30. (20). If medical therapy fails in pain
relief or the pain score according to VAS is seven or
more, hysterectomy with or without bilateral salpingo-
oophorectomy can be suggested to women who have
completed their families (20,21).
According to R. M Kho et al. comparison of the major
society guidelines, assisted reproductive techniques
should be the first choice if fertility is the main
symptom. Surgery is advised if IVF fails twice (20).
The excision of deep endometriosis before assisted
reproductive techniques has been shown to increase
fertility in endometriosis stages I and II, despite the
major guidelines suggesting that surgery should only
be performed if IVF fails twice. This is because
surgery aims to restore normal pelvic anatomy and
remove macroscopic implants (26,27). According to a
comprehensive review and meta-analysis by G. Casals
et al., surgery improves the success of IVF. However,
predicting the precise effect of eliminating DE is
challenging because it frequently coexists with
ovarian endometriosis and adenomyosis. The authors
also state the lack of randomized controlled trials on
this topic (28).
4. Conclusion
DE diagnosis should take into account symptoms,
medical background, digital assessment, and imaging.
TVUS has a high diagnostic value for DE of the
uterosacral ligaments, intestine, and vaginal rectal
septum but largely depends on the location of
endometriosis and the doctor's experience. The use of
#Enzian classification improves the accuracy of
TVUS. Sonography is regarded as the primary
diagnostic method, with MRI being employed for
locations where TVUS is less sensitive. This means
diagnostic laparoscopy with tissue biopsy should only
be utilized as a last-resort approach when TVUS and
MRI results are ambiguous, and symptoms worsen.
The first-line treatment for DE should be
pharmaceutical therapy, preferably starting with
Dienogest. However, the main problem with medical
therapy is that it has little effect on already existing
lesions, and symptoms tend to recur when therapy is
terminated. Assisted reproductive techniques should
be considered for patients whose primary symptom is
infertility. Surgery should only be considered when
medical treatment or IVF fails.
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