1. Endometriosis Update (Clinic)
Dr.Engin Oral
Cerrahpaşa Medical Faculty
Department of Obstet & Gynecology
Div of Reproductive Endocrinology

6. Endometriosis: Diagnosis process
4,334 women reporting
surgically diagnosed endometriosis
Onset of Time from seeking symptoms medical attention to diagnosis
Adolescents 6.0 ± 0.2 years
Adults ± 0.3 years
Onset of symptoms
Adolescents 67.1%
Adults %
Objective: To determine whether first physician seen and symptoms beginning in adolescence have an impact on
the diagnostic experience of endometriosis.
Design: Cross-sectional study of self-reported survey data.
Setting: Academic research.
Patient(s): Four thousand three hundred thirty-four Endometriosis Association Survey respondents reporting surgical
diagnosis of endometriosis.
Intervention(s): None.
Main Outcome Measure(s): Specialty of first physician seen, timing of onset of symptoms, time to seeking medical
care and to diagnosis, number of physicians seen, and satisfaction with care.
Result(s): Almost all respondents reported pelvic pain. Fifty percent first saw a gynecologist and 45% saw a generalist
for symptoms related to endometriosis. Two thirds reported symptoms beginning during adolescence; they
waited longer to seek medical care than adults did. Those seeing a generalist first took longest to get diagnosed;
those seeing a gynecologist first saw fewer physicians. Sometime before diagnosis, 63% were told nothing was
wrong with them.
Conclusion(s): Women and girls who reported seeing a gynecologist first for symptoms related to endometriosis
were more likely to have a shorter time to diagnosis, to see fewer physicians, and to report a better experience overall
with their physicians. The majority reported symptoms beginning during adolescence, also reporting a longer
time and worse experience while obtaining a diagnosis.
Greene R, 2009

7. 2009

8. Markham R. Endometriosis symptoms in Australian women
(PhD Thesis). The University of Sydney
Markham R. Endometriosis symptoms in Australian women (PhD Thesis). The University of Sydney

9. Deep Endometriosis: Symptoms
OBJECTIVE: To examine the short-term surgical outcomes in women undergoing fertility-sparing laparoscopic excision of deeply infiltrating pelvic endometriosis. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center for treatment of endometriosis, a university teaching hospital, London, United Kingdom. PATIENT(S): A total of 177 women who underwent fertility-sparing laparoscopic excision of deeply infiltrating endometriosis between January 1, 2006, and December 31, INTERVENTION(S): Eligible women were identified from the surgeons' database, and their medical notes were reviewed. Data from preoperative assessment, surgery, and postoperative outcomes were analyzed. MAIN OUTCOME MEASURE(S): Complication rate. RESULT(S): One hundred seventy-seven women underwent fertility-sparing laparoscopic excision of deeply infiltrating endometriosis including excision of uterosacral ligaments (43, 24.3%), excision of rectovaginal septum (56, 31.6%), rectal shave (56, 31.6%), disk excision (7, 4%) or bowel resection (15, 8.5%). The median operative time was 95 minutes with a range of 30 to 270 minutes (interquartile range minutes). Overall, complications developed in 18 women (10.2%). In 12 (6.8%) of these only uncomplicated pyrexia developed whereas significant intraoperative and/or postoperative complications developed in the remaining 6 (3.4%). Women spent a median of 2 days recovering in hospital (range 1-7, interquartile range 2-3 days). CONCLUSION(S): Fertility-sparing laparoscopic excision of deeply infiltrating endometriosis appears to be safe with a low short-term complication rate.
Pandis GK, 2010

10. Diagnosis of Endometriosis
History (The most important)
Symptoms
Physical Examination (not much help)
Serum Markers (Lacks sensitivity)
Ultrasound (of little value except endometrioma)
Magnetic Resonance Imaging (MRI) (a good guess!)
Other Imaging Modalities
immunoscintigraphy and positron emission tomography
Transvaginal Hydrolaparoscopy
Laparoscopic Visualization of the Pelvis (The gold standard)
Biopsy Preferable Over Visual Inspection
Novel Diagnostic Test
The typical patient with endometriosis presents with a history of chronic
pelvic pain or infertility or both (Table 11-3). The pelvic pain can be quite
of endometriosis often begins 1 to 2 days before the onset of menses and continues
menses beginning years after menarche) (see Chapter 12). The dysmenorrhea
variable, but the classic symptom is secondary dysmenorrhea (i.e., painful
throughout the duration of bleeding. The pain most likely stems from
septum, and uterosacral ligaments, patients may also complain of
endometriosis involves the deeper aspects of the posterior cul-de-sac, rectovaginal
prostaglandin secretion by the ectopic endometrial tissue and, while typically intermittent and cyclic, in some women the pain may be continuous. When
dysuria, dyschezia, backache, and dyspareunia, especially with deep penetration.
(Table 11-4).
with disorders of the genitourinary tract or gastrointestinal system
Many symptoms of pelvic endometriosis therefore overlap with those associated
few days before the onset of normal menstrual flow. One should therefore elicit
Patients may also report cyclic premenstrual spotting beginning within a
may be abrupt, an insidious onset with gradual worsening of pelvic pain over
relationship to menses. Although the onset of the secondary dysmenorrhea
a menstrual history as well as a careful description of the pain and its precise
successive menses is more typical of endometriosis. A presentation of acute
stones, and diverticulitis be excluded (see Chapter 9). A menstrual diary is often
(PID), adnexal torsion, hemorrhagic luteal cysts, urinary tract infections, renal
onset of pain requires that such processes as pelvic inflammatory disease
useful to record the timing of the pain and any premenstrual spotting.
or longer duration of menses. However, not all patients with endometriosis
and elucidate any potential risk factors such as short menstrual cycle intervals
One should also inquire whether there is a family history of endometriosis
have risk factors. One should also carefully question the patient regardingsymptoms related to the urinary and gastrointestinal tracts to help exclude
with endometriosis to describe
It is not uncommon for the patient
these potential sources of the pelvic pain.
offices or emergency rooms where
prior visits to physician
One should not be misled by this
such diagnoses as cystitis or PID.
her symptoms were attributed to
history, however, and one should
(sometimes repeatedly) by a presumptive
endometriosis are stigmatized
recognize that many patients with
diagnosis of PID. These
chronic pelvic pain and incorrect diagnoses and to educate the patient regarding
time in the office visit to validate the emotional responses to both the
patients often benefit from additional
the challenge of diagnosing endometriosis.
when performed just before or during menstruation, when lesions are
should precede the pelvic exam. The pelvic exam often yields the most findings
A general physical examination, including careful attention to the abdomen,
in the vagina, it can occasionally be seen in the vaginal fornices or cervical
most active and symptoms most severe. Although endometriosis is uncommon
chronic pelvic pain, any abnormal vaginal discharge or evidence of cervical
and a histologic diagnosis obtained. To exclude infections as the source of the
canal as small, bluish, grape-like nodules. Any lesions should be biopsied
inflammation requires further investigation; even in the absence of exam
motion tenderness. Adnexal fullness and tenderness may represent an endometrioma
Bimanual exam may reveal tenderness in the vaginal fornices or cervical
findings, cervical specimens for chlamydia and gonorrhea are usually sent.
due to endometriosis in the posterior cul-de-sac. The rectovaginal exam
of the ovary. A retroverted, fixed uterus is suggestive of adhesions
anterior vaginal wall is more likely due to a primary urological process such
uterosacral ligaments and cul-de-sac peritoneum. Isolated tenderness in the
is essential, because it may demonstrate thickening or nodularity of the
as bladder disease, urethritis, or an urethral diverticulum.
excluded. The patient who is menstruating is given three guaic cards to complete
positive test may be due to endometriosis, but it should be assumed to resultfrom a primary gastrointestinal lesion until such pathology is appropriately
If the patient is not menstruating, a stool guaic should be performed. A
The CA-125 is a high-molecular-weight glycoprotein expressed on the cell
at home and return.
pancreatitis, chronic liver disease, and during pregnancy or
in women with epithelial ovarian cancers, pelvic infections, uterine fibroids,
surface of derivatives of embryonic coelomic epithelium. While commonly elevated
menstruation, it is also a marker for endometriosis (29). One study reported
range in women that have only mild or minimal disease, and in general this
greater than 16 U/mL (29). However, the CA-125 may be in the normal
that 80% of women with pain and endometriosis had a serum CA-125 concentration
marker lacks adequate sensitivity and specificity for general use as a diagnostic
signal disease recurrence, and for those patients with infertility, a low postoperative
surgical treatment for their endometriosis, serial monitoring may help
tool (30). However, for patients with elevated levels who subsequently undergo
CA-125 concentration predicts greater likelihood of spontaneous
endometriomas detected on pelvic exam. These ovarian cysts may be
A pelvic transvaginal ultrasound is often useful in confirming ovarian
pregnancy (31).
They tend to persist and often become quite large. When a
unilocular or septated and typically have a sonographic “ground glass” appearance.
cyst is at risk for rupture, which causes acute pelvic pain from irritation of
often plans are made for its surgical drainage and resection. Such a
“chocolate” cyst (named such for its content of brown blood debris) is diagnosed,
the peritoneum by the “chocolate” material contained inside. The subsequent
Laparoscopy is an outpatient surgical procedure often used to confirm the diagnosis
particularly difficult to dissect.
inflammatory response can result in dense adhesions that may be
placement of a laparoscope 2 to10 mm in diameter through a puncture
of endometriosis and allow for surgical treatment. The procedure involves
with carbon dioxide to elevate the anterior abdominal wall and permit
in diameter, are placed in the lower abdomen. The peritoneal cavity is then insufflated
site in the umbilicus. One to three more puncture sites, usually 5 to 12 mm
visualization of the lower pelvis. General anesthesia is most often used;
shoulder pain due to diaphragmatic irritation from the carbon dioxide, and
following the procedure include mild pelvic discomfort, occasional
however, the patient usually goes home within a few hours after the procedure and is back to work or normal home activities within 24 to 48 hr. Side effects
laparoscopy, which can be performed without general anesthesia, and office
anesthetic sequelae. Newer techniques to visualize the pelvis include gasless
The “classic” laparoscopic appearance of endometriosis is a blue or black
intraperitoneal gas insufflation, and intravenous sedation.
laparoscopy using a smaller (2 mm) diameter laparoscope, small amounts of
lesion with a “powder burn” appearance. Other presentations include white,
most active (32). Clear, vesicular lesions are usually seen in younger women
previous pelvic infections, and reddish, hemorrhagic lesions, which are the
“scarred” lesions resembling old operative scars or fibrotic remnants from
and probably represent early disease (32). These lesions are also difficult to
Lesions may invade as deeply as 5 mm into the peritoneum or remain as superficial
Biopsies should be taken from lesions to help confirm the diagnosis.
visualize during laparoscopy unless it is performed by an experienced laparoscopist.
as 1 to 2 mm (32), and it is often difficult to appreciate the depth of
cancer cells, epithelial inclusion cysts, residual carbon from previous
include hemangiomas, old sutures, necrotic areas from old ectopic pregnancies,
an endometriotic implant. Lesions commonly mistaken for endometriosis
inflammatory cysts (32).
laser surgery or coagulation devices, hysterosalpingogram dye reaction, and
from the rupture of endometriomas. Adhesions may completely obliterate the
These typically result from the inflammatory process of endometriosis or
Adhesions are another common finding in patients with endometriosis.
cul-de-sac or adnexae and involve the bowel (33). Though adhesions represent
surgeon to resort to a laparotomy at a later date following adequate bowel
In some cases, the extent of adhesions may prohibit laparoscopy, forcing the
an important cause of infertility, they generally do not cause pelvic pain.
The American Society for Reproductive Medicine (formerly the American
preparation.
severity based on extent and size of peritoneal disease, ovarian involvement,
(Table 11-5) (34). In this classification, endometriosis is divided into stages of
Fertility Society) has classified endometriosis based on surgical findings
and severity of adhesions involving the ovaries and fallopian tubes; thus the
Nonetheless, the classification system provides a framework for the surgeon
that it makes little attempt to designate the expected degree of pelvic pain.
system attempts to quantitate the effect on fertility. A major shortcoming is
and allows for objectivity and standardization, and therefore is included in the
to document the location and size of lesions as well as the extent of adhesions,
operative report.
Rule out other Causes of Symptoms (The next most important)

11. BRANDI S. MCLEOD, and MATTHEW G. RETZLOFF, 2010

12. Sites of Endometriosis: Associated Signs & Symptoms
Female reproductive organs (for example: ovaries, uterus, vagina,
fallopian tubes, pelvic peritoneum)
Dysmenorrhea (painful menstruation)
Dyspareunia (pain during or after sexual intercourse)
Infertility
Pelvic pain
Backache
Menstruel irregularity
Ruptured endometrioma
Surgical scars umbilicus
Cyclic pain and bleeding

13. Sites of Endometriosis: Associated Signs & Symptoms
Gastrointestinal system (for example: rectum, small intestine, colon)
Nausea and vomiting
Abdominal cramping
Diarrhea
Constipation
Blood in stool
Pain in the low back or tailbone
Pain in the umbilicus
Abdominal bloating and cramping
Rectal bleeding
Defecation problems

14. Sites of Endometriosis: Associated Signs & Symptoms
Urinary tract (for example: bladder, ureter, urethra, kidney)
Pain or burning upon urination
Urinary frequency, urgency, or retention
Blood in the urine
Flank pain
Recurrent complaints of urinary tract infections with negative cultures
Pulmonary (for example: lungs, pleura, diaphragm)
Chest or shoulder pain
Coughing up blood
Shortness of breath

15. SERENA DOVEY, and JOSEPH SANFILIPPO, 2010

16. Endometriomas in adolescents
Objective: To report a rare presentation of bilateral endometriomas in an adolescent and describe characteristics of
endometriomas.
Design: Case report.
Setting: Major academic medical center.
Patient(s): An 18-year-old G0 presented with an incidentally found 35-cm pelvic mass that was found to be bilateral
Intervention(s): Exploratory laparotomy with resection of endometrioma cyst walls and lysis of adhesions.
Main Outcome Measure(s): The incidence, pathogenesis, fertility implications, and treatment options for endometriomas
in adolescents.
Result(s): Endometriomas are rare in adolescents. There are no case reports in the literature to date.
Conclusion(s): Endometriosis should be considered in adolescents presenting with bilateral complex ovarian
masses regardless of their size
CA-125 of 379 and an elevated lactate
dehydrogenase (LDH) of 245.
Kelly Nicole Wright, 2010

17. Deep pelvic endometriosis
Figure 1. Transvaginal sonography showing occlusion of the
Douglas pouch due to endometriotic ®brosis (F) involving the rectal
wall. R = rectum; U = uterus; C = cervix.
Figure 3. The sequential US appearance of pathologically diagnosed rectosigmoid endometriosis
in a 32-year-old woman who had haematochezia and dyschezia (patient 5 in Table I). TV US
image at her ®rst visit (a), The lesion
decreased in size and lost its central hypoechoic area after subsequent spontaneous pregnancy and
childbirth (c). The change was accompanied by the relief of the patient's symptoms.
Transvaginal sonographic sagittal image in a 25-year-old
woman with rectum/sigmoid colon endometriosis. The adipose
tissue plane lying between the uterus and the rectum/sigmoid colon
is absent. The hypoechogenic aspect of the muscularis propria of
the rectum/sigmoid colon (arrowheads) has disappeared, to be
replaced by an abnormal hypoechogenic mass (arrow) located just
behind the uterus. Note the presence of uterine adenomyosis.

18. Three-Dimensional Sonographic Characteristics of Deep Endometriosis
Objective. The purpose of this presentation is to investigate the potential role of 3-dimensional (3D)
sonography in the assessment of deep endometriosis. Methods. Cases of deep endometriosis are presented
to illustrate the spectrum of appearances obtained with 3D sonography. In addition, we evaluate
the possible role of other functions included in 3D equipment, such as the niche mode and
tomographic ultrasound imaging (TUI). Results. Three-dimensional image rendering could allow a
good analysis of the endometriotic nodule; in fact, in all presented cases, this reconstruction seems to
clearly show the irregular shapes and borders of the lesions. This technique allows unrestricted access
to an infinite number of viewing planes, which can be very useful for correctly locating lesions within
the pelvis and evaluating the relationship with other organs. The stored 3D volumes can be reassessed
and compared by the same or different examiners over time. This characteristic may be relevant for
monitoring the effect of medical therapies over time. In the niche mode, sonographic imaging is represented
as a “cut-open” view of the internal aspect of the nodule and its surrounding tissue. This
additional function, which is associated with TUI, could be particularly useful for evaluation of the
extension of a nodule in the rectovaginal septum, the depth of infiltration, and the relationship with
the rectosigmoid junction or ureter. Conclusions. In the near future, 3D sonography in deep infiltrating
endometriosis could be an interesting mode of research with positive effects in everyday clinical
practice.
Magnified rendered axial view of a rectosigmoid nodule
in deep endometriosis (arrows) from a 33-year-old woman
(same patient as in Figure 2) showing a clear definition of the
mass, which seems relatively less irregular in shape and borders
compared with Figure 3.
Magnified rendered axial view of a rectovaginal nodule
in deep endometriosis (arrows) from a 24-year-old woman
(same patient as in Figure 1) showing a clear definition of the
mass, which seems irregular in shape and borders. The bowel
(Bo), vagina (Va), and cervix (Ce) are shown.
Stefano Guerriero, 2009

19. Posterior pelvis endometriosis MRI
Figure 1. Axial T2-weighted spin echo magnetic resonance image of a 32-year-old patient complaining about
dyspareunia. The right uterosacral ligament demonstrates nodular thickening with spiculated borders (black
arrow). Histology after surgical resection diagnosed endometriosis of the right uterosacral ligament.
The right uterosacral ligament demonstrates nodular thickening with spiculated borders
(black arrow). Histology after surgical resection diagnosed endometriosis of the right
uterosacral ligament.

20. Diagnostic accuracy of physical examination, transvaginal sonography, rectal endoscopic sonography, and magnetic resonance imaging to diagnose deep infiltrating endometriosis
N:92
Objective: To compare the value of physical examination, transvaginal sonography (TVS), rectal endoscopic
sonography (RES), and magnetic resonance imaging (MRI) for the assessment of different locations of deep infiltrating
endometriosis (DIE).
Design: Retrospective longitudinal study.
Setting: Tertiary university gynecology unit.
Patient(s): Ninety-two consecutive patients with clinical evidence of pelvic endometriosis.
Intervention(s): Physical examination, TVS, RES, and MRI, performed preoperatively.
Main Outcome Measure(s): Descriptive statistics, calculation of likelihood ratios (LRş and LR) of physical
examination, TVS, RES, and MRI for DIE in specific locations confirmed by surgery/histology.
Result(s): The sensitivity and LRş and LR values of physical examination, TVS, RES, and MRI were, respectively,
73.5%, 3.3, and 0.34, 78.3%, 2.34, and 0.32, 48.2%, 0.86, and 1.16, and 84.4%, 7.59, and 0.18 for uterosacral
ligament endometriosis; 50%, 3.88, and 0.57, 46.7%, 9.64, and 0.56, 6.7%, -, and 0.93, and 80%, 5.51, and 0.23 for
vaginal endometriosis; and 46%, 1.67, and 0.75, 93.6%, -, and 0.06, 88.9%, 12.89, and 0.12, and 87.3%, 12.66, and
0.14 for intestinal endometriosis.
Conclusion(s): The MRI performs similarly to TVS and RES for the diagnosis of intestinal endometriosis but has
higher sensitivity and likelihood ratios for uterosacral ligament and vaginal endometriosis
Marc Bazot, 2009

21. Urinary tract endometriosis (UTE)
Urinary tract endometriosis (UTE) includes the presence of endometrial tissue in or around the bladder, ureters, urethra, or kidney. This disease, once considered to be a rare clinical entity, is now increasingly recognized .
Recently, its incidence was estimated to range from 0.3% to 6% among women with endometriosis . The percentage of bladder involvement in these cases is 84%–90% .
Within the urinary system, the bladder is the most commonly affected (80%-84%), followed by the ureter (15%), kidney (4%), and urethra (2%).
In the bladder, the retrotrigone and dome are the most frequently affected sites. Two possible ureteral lesions must be considered:intrinsic and extrinsic.
The extrinsic form is
more common and is characterized by contiguity involvement
of the ureter, compressing and causing fibrosis of
the ureteral structures, and impairing function of the
kidney in 30% of cases. The intrinsic lesions originate
from lymphatic or venous metastases14 and can manifest
as obstructive conditions or result in cyclic hematuria
when the ureteral mucosa is affected.

22. Endometriosis of the bladder
Fig. 5. Endometriosis of the bladder. US and MRI with GRE
FSE T1 sequences. A, B US images, performed with a transabdominal
approach, highlight a large intramural nodule (between
calipers), with an approximately 3-cm major axis and
solid hypoechoic structure. A thin hyperechoic band between
the mass and the vesical lumen confirms the lesion’s extramucosal
site. MR images in the coronal (C) and axial (D)
planes show the nodule (arrows) at the posterior bladder wall,
characterized by an isointense signal. Hyperintense microfoci
are visible around the lesion.

23. Endoscopic view of bladder endometriosis

24. Abdominal Wall Endometriomas Near Cesarean Delivery Scars
Abdominal wall endometrioma (7 mm) fully encircled
by a hyperechoic ring (arrows).
Large (50-mm) subcutaneous endometrioma in a 22-
year-old woman showing an irregular shape and complex echo
texture due to the presence of small cystic areas (arrowheads).
Giampiero Francica, 2003

25. Fine-Needle Aspiration Cytology of Scar Endometriosis: Study of Seven Cases And Literature Review
Fig. 1. On FNAC, epithelial endometrial-like cells (a), endometrial-like stromal cells (b), two with decidualization (c), and hemosiderin-laden macrophages
(d). [Color figure can be viewed in the online issue, which is available at is defined as the presence of endometrial-like
glands and stroma outside the uterine endometrial lining. Endometrial
tissue has also been identified in numerous surgical or
procedure scars, including cesarean section and laparoscopic
trocar tract.
A prospective study was conducted at Maternidade-Escola
Assis Chateaubriand, Faculty of Medicine, Federal University of
Ceara, Brazil in seven patients with abdominal wall mass pathologically
proven as scar endometriosis from January 2004 to
December All cases were submitted to fine-needle aspiration
cytology (FNAC).
Age ranged from 21 to 42 years old (mean: 30) with parity
ranging from 0 to 3 (mean: 1.4). The preceding history of pelvic
procedures was miomectomy (1 of 7), cesarean section (3 of 7),
and diagnostic laparoscopy (3 of 7). The complaints occurred
about 18 months after the surgical proceeding. The FNAC findings
were endometrial-like epithelial cells (6 of 7) and stromal cells (6
of 7); decidualization occurred in 2 of 7 cases. Hemosiderin-laden
macrophages were present in all cases. FNAC is a fast and accurate
method to make the diagnosis before the surgery, avoiding
errors in the approach of the abdominal wall endometriosis’ scars.
Even when symptomatic, endometriosis of the abdominal
wall is difficult to diagnose. Its clinical diagnosis has
been confused with abscess, lipoma, hematoma, sebaceous
cyst, suture granuloma, inguinal hernia, incisional hernia,
desmoid tumor, sarcoma, lymphoma, or primary and metastatic
cancer.12 Fine-needle aspiration cytology (FNAC)
is indicated when the clinical diagnosis is in doubt.13
Francisco das Chagas Medeiros

27. Comparison of the clinical value of CA 19-9 versus CA 125 for the diagnosis of endometriosis
Preoperative blood samples and intraoperative tissue specimens were obtained from 101 patients with endometriosis
and 78 patients without endometriosis referred for benign gynecologic operations to investigate the clinical
value of serum and tissue CA 19-9 levels in the diagnostic evaluation of endometriosis as compared to CA 125.
Our prospective cohort study showed that serum CA 19-9 is a valuable marker in the diagnosis of endometriosis,
and it may be used to predict the patients with severe endometriosis when used with CA 125.
Zehra Kurdoglu, 2009

28. The role of microRNAs in endometriosis
background: microRNAs (miRNAs) are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level.
Recent research has shown that miRNAs and their target mRNAs are differentially expressed in endometriosis and other disorders of the
female reproductive system. Since miRNAs control a broad spectrum of normal and pathological cellular functions, they may play pivotal
roles in the pathogenesis of these disorders.
methods: A systematic review was undertaken of the published literature on; (i) the expression and functions of miRNAs in mammalian
female reproductive tissues with a focus on endometriosis and the malignancies and fertility disorders related to this disease; and (ii) the
potential roles played by validated mRNA targets of endometriosis-associated miRNAs. The current understanding of the biology of
miRNAs is overviewed and the potential diagnostic and therapeutic potential of miRNAs in endometriosis is highlighted.
results: The differential expression of miRNAs in endometriosis, and the putative molecular pathways constituted by their targets,
suggests that miRNAs may play an important role in endometriotic lesion development. Models for miRNA regulatory functions in endometriosis
are presented, including those associated with hypoxia, inflammation, tissue repair, TGFb-regulated pathways, cell growth, cell proliferation,
apoptosis, extracellular matrix remodelling and angiogenesis. In addition, specific miRNAs which may be associated with malignant
progression and subfertility in endometriosis are discussed.
conclusions: miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders,
raising the prospect of using miRNAs as biomarkers and therapeutic tools in endometriosis.
E. Maria C. Ohlsson Teague, 2010

29. Epigenetics of endometriosis
abstract: Endometriosis is a common gynecologic disorder with an enigmatic etiopathogenesis. Although it has been proposed that
endometriosis is a hormonal disease, an autoimmune disease, a genetic disease, and a disease caused by exposure to environmental
toxins, our understanding of its etiopathogenesis is still inadequate, as reflected by recent apparent setbacks in clinical trials on endometriosis.
In the last 5 years, evidence has emerged that endometriosis may be an epigenetic disease. In this article, the evidence in support of this
hypothesis is reviewed, and its diagnostic, therapeutic and prognostic implications discussed. Publications, up to the end of June 2009, pertaining
to epigenetic aberration in endometriosis were identified through PubMed. In addition, publications on related studies were also
retrieved and reviewed. Epigenetics appears to be a common denominator for hormonal and immunological aberrations in endometriosis.
Epigenetics also appears to have a better explanatory power than genetics. There is accumulating evidence that various epigenetic aberrations
exist in endometriosis. In vitro studies show that histone deacetylase inhibitors may be promising therapeutics for treating endometriosis. In
conclusion, several lines of evidence suggest that epigenetics plays a definite role in the pathogenesis and pathophysiology of endometriosis.
As such, endometriosis is possibly treatable by rectifying epigenetic aberrations through pharmacological means. DNA methylation markers
may also be useful for diagnostic and prognostic purposes. It is also possible that the delineation of the epigenetic changes accompanied by
the genesis and progression of endometriosis could lead to interventions that reduce the risk of developing endometriosis
Sun-Wei Guo, 2009

30. Combination of CCR1 mRNA, MCP1, and CA125 Measurements in Peripheral Blood as a Diagnostic Test for Endometriosis
sensitivity of 92.2%, a specificity of 81.6%, a negative predictive value of 83.3%, a positive predictive value of 92.3%, a likelihood ratio of a positive test result of 5.017, and a likelihood ratio of a negative test result of to predict the presence or absence of endometriosis.
This study investigated the possible use of CCR1 mRNA measurement in peripheral blood leukocytes
in combination with measurements of monocyte chemotactic protein-1 (MCP-1) and CA125 protein
in serum as a diagnostic test for endometriosis.The expression of CCR1 mRNA in peripheral blood
leukocytes was measured by quantitative real-time polymerase chain reaction. MCP-1 and CA125 levels
in serum were determined by ELISA and ECLIA.The ratio of CCR1/HPRT mRNA in peripheral
blood of patients with endometriosis and adenomyosis was significantly elevated compared with
women without endometriosis. Additionally, serum levels of MCP-1 and CA125 were significantly
higher in patients with endometriosis. This method showed a sensitivity of 92.2%, a specificity of
81.6%, a negative predictive value of 83.3%, a positive predictive value of 92.3%, a likelihood ratio
of a positive test result of 5.017, and a likelihood ratio of a negative test result of to predict the
presence or absence of endometriosis.The results imply the potential use of CCR1 mRNA, MCP-1,
and CA125 protein measurements for the diagnosis or exclusion of endometriosis
Admir Agic, 2010

31. Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers
interleukin (IL)-6, IL-8, tumour necrosis factor-alpha, high-sensitivity C-reactive
protein (hsCRP), and cancer antigens CA-125 and CA-19-9
background: Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis.
The aim of this study was to evaluate the combined performance of six potential plasma biomarkers in the diagnosis of endometriosis.
methods: This case–control study was conducted in 294 infertile women, consisting of 93 women with a normal pelvis and 201 women
with endometriosis. We measured plasma concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha, high-sensitivity C-reactive
protein (hsCRP), and cancer antigens CA-125 and CA Analyses were done using the Kruskal–Wallis test, Mann–Whitney test,
receiver operator characteristic, stepwise logistic regression and least squares support vector machines (LSSVM).
results: Plasma levels of IL-6, IL-8 and CA-125 were increased in all women with endometriosis and in those with minimal–mild endometriosis,
compared with controls. In women with moderate–severe endometriosis, plasma levels of IL-6, IL-8 and CA-125, but also of
hsCRP, were significantly higher than in controls. Using stepwise logistic regression, moderate–severe endometriosis was diagnosed with
a sensitivity of 100% (specificity 84%) and minimal–mild endometriosis was detected with a sensitivity of 87% (specificity 71%) during
the secretory phase. Using LSSVM analysis, minimal–mild endometriosis was diagnosed with a sensitivity of 94% (specificity 61%) during
the secretory phase and with a sensitivity of 92% (specificity 63%) during the menstrual phase.
conclusions: Advanced statistical analysis of a panel of six selected plasma biomarkers on samples obtained during the secretory
phase or during menstruation allows the diagnosis of both minimal–mild and moderate–severe endometriosis with high sensitivity and clinically
acceptable specificity
A. Mihalyi, 2009

32. Peripheral biomarkers of endometriosis: a systematic review
background: Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the
diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is
simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be
monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment
failure at an early stage.
methods: We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature
over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine.
results: We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single
biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful.
conclusions: Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended
in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test.
Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care.
Panels of markers may allow increased sensitivity and specificity of any diagnostic test.
K.E. May, 2010

33. Visual representation of nerve fibers present in the endometrium using neuronal markers.
MELISSA G. MEDINA, 2009

34. A pilot study to evaluate the relative efficacy of endometrial biopsy and full curettage in making a diagnosis of endometriosis by the detection of endometrial nerve fibers
Endometrial biopsies with precise, consistent technique and curettings were taken from 37 women (20 with endometriosis and 17 without endometriosis).
Small nerve fibers were detected in all endometrial biopsies and curettings from all 20 women with endometriosis, but were not detected in endometrium taken from 17 women without endometriosis
OBJECTIVE: The purpose of this study was to evaluate endometrial
biopsy and curettage in detecting small nerve fibers in eutopic endometrium
for diagnosis of endometriosis.
STUDY DESIGN: Endometrial biopsies with precise, consistent technique and
curettings were taken from 37 women (20 with endometriosis and 17 without
endometriosis). Sensitivity, specificity, and positive and negative predictive
value were formally calculated. Endometrial nerve fibers were immunohistochemically
detected using the pan-neuronal marker PGP9.5.
RESULTS: Small nerve fibers were detected in all endometrial biopsies
and curettings from all 20 women with endometriosis, but were not
detected in endometrium taken from 17 women without endometriosis.
Mean (SD) nerve fiber density in the endometrial biopsies was 26.8
per mm (range, ) and for curettings was 21.6 per mm2
33.1 (range, ), with 100% specificity, sensitivity, and positive
and negative predictive value.
CONCLUSION: Careful endometrial biopsy combined with immunohistochemical
staining for nerve fibers may be a reliable means of diagnosing
or excluding endometriosis
FIGURE 3
Distribution of endometrial
nerve fibers in the eutopic
endometrium in a woman who
underwent hysterectomy for
endometriosis
Moamar Al-Jefout, 2007

35. Diagnosis of endometriosis by detection of nerve fibres in an endometrial biopsy: a double blind study
background: Diagnosis of endometriosis currently requires a laparoscopy and this need probably contributes to the considerable
average delay in diagnosis. We have reported the presence of nerve fibres in the functional layer of endometrium in women with endometriosis,
which could be used as a diagnostic test. Our aim was to assess efficacy of nerve fibre detection in endometrial biopsy for making a
diagnosis of endometriosis in a double-blind comparison with expert diagnostic laparoscopy.
methods: Endometrial biopsies, with immunohistochemical nerve fibre detection using protein gene product 9.5 as marker, taken from
99 consecutive women presenting with pelvic pain and/or infertility undergoing diagnostic laparoscopy by experienced gynaecologic laparoscopists,
were compared with surgical diagnosis.
results: In women with laparoscopic diagnosis of endometriosis (n ¼ 64) the mean nerve fibre density in the functional layer of the
endometrial biopsy was 2.7 nerve fibres per mm2 (+3.5 SD). Only one woman with endometriosis had no detectable nerve fibres. Six
women had endometrial nerve fibres but no active endometriosis seen at laparoscopy. The specificity and sensitivity were 83 and 98%,
respectively, positive predictive value was 91% and negative predictive value was 96%. Nerve fibre density did not differ between different
menstrual cycle phases. Women with endometriosis and pain symptoms had significantly higher nerve fibre density in comparison with
women with infertility but no pain (2.3 and 0.8 nerve fibre per mm2, respectively, P ¼ 0.005).
conclusions: Endometrial biopsy, with detection of nerve fibres, provided a reliability of diagnosis of endometriosis which is close to
the accuracy of laparoscopic assessment by experienced gynaecological laparoscopists.
M. Al-Jefout1, 2009

36. Density of small diameter sensory nerve fibres in endometrium: a semi-invasive diagnostic test for minimal to mild endometriosis
Secretory phase endometrium samples (n 40), obtained from women with laparoscopically/histologically confirmed minimal–mild endometriosis (n 20) and from women with a normal pelvis (n 20) were selected
The density of small nerve fibres was 14 times higher in endometrium from patients with minimal–mild endometriosis ( ) when compared with women with a normal pelvis ( , P , ).
The combined analysis of neural markers PGP9.5, VIP and SP could predict the presence of minimal–mild endometriosis with 95% sensitivity, 100% specificity and 97.5% accuracy.
background: The aim of our study was to test the hypothesis that multiple-sensory small-diameter nerve fibres are present in a higher
density in endometrium from patients with endometriosis when compared with women with a normal pelvis, enabling the development of a
semi-invasive diagnostic test for minimal–mild endometriosis.
methods: Secretory phase endometrium samples (n ¼ 40), obtained from women with laparoscopically/histologically confirmed
minimal–mild endometriosis (n ¼ 20) and from women with a normal pelvis (n ¼ 20) were selected from the biobank at the Leuven University
Fertility Centre. Immunohistochemistry was performed to localize neural markers for sensory C, Ad, adrenergic and cholinergic nerve
fibres in the functional layer of the endometrium. Sections were immunostained with anti-human protein gene product 9.5 (PGP9.5), antineurofilament
protein, anti-substance P (SP), anti-vasoactive intestinal peptide (VIP), anti-neuropeptide Y and anti-calcitonine gene-related
polypeptide. Statistical analysis was done using the Mann–Whitney U-test, receiver operator characteristic analysis, stepwise logistic
regression and least-squares support vector machines.
results: The density of small nerve fibres was 14 times higher in endometrium from patients with minimal–mild endometriosis
( ) when compared with women with a normal pelvis ( , P , ).
conclusions: The combined analysis of neural markers PGP9.5, VIP and SP could predict the presence of minimal–mild endometriosis
with 95% sensitivity, 100% specificity and 97.5% accuracy. To confirm our findings, prospective studies are required.
A. Bokor, 2009

37. Rich innervation of deep infiltrating endometriosis
DIE (n 31) and peritoneal endometriotic (n 40) lesions were sectioned
There were significantly more nerve fibres in DIE ( /mm2) than in peritoneal endometriotic lesions ( /mm2) (P , 0.01).
background: Deep infiltrating endometriosis (DIE) is a specific type of endometriosis, which can be associated with more severe
pelvic pain than other forms of endometriotic lesions. However, the mechanisms by which pain is generated are not well understood.
methods: DIE (n ¼ 31) and peritoneal endometriotic (n ¼ 40) lesions were sectioned and stained immunohistochemically with antibodies
against protein gene product 9.5, neurofilament, nerve growth factor (NGF), NGF receptors tyrosine kinase receptor-A (Trk-A)
and p75, substance P, calcitonin gene-related peptide, vesicular acetylcholine transporter, neuropeptide Y, vasoactive intestinal peptide
and tyrosine hydroxylase to demonstrate myelinated, unmyelinated, sensory and autonomic nerve fibres.
results: There were significantly more nerve fibres in DIE ( /mm2) than in peritoneal endometriotic lesions ( /
mm2) (P , 0.01). DIE was innervated abundantly by sensory Ad, sensory C, cholinergic and adrenergic nerve fibres; NGF, Trk-A and p75
were strongly expressed in endometriotic glands and stroma of DIE.
conclusions: The rich innervation of DIE may help to explain why patients with this type of lesion have severe pelvic pain.
Figure 2 Densities of nerve fibres (mean+SD) in DIE and superficial
peritoneal endometriosis.
The density of nerve fibres stained with PGP9.5 in DIE was significantly greater
than that in superficial peritoneal endometriosis (*P , 0.01). The density of
nerve fibres stained with NF in DIE was also significantly greater than that in
superficial peritoneal endometriosis (**P , 0.01).
Guoyun Wang, 2009

38. A pilot study to evaluate the clinical relevance of endometriosis-associated nerve fibers in peritoneal endometriotic lesions
Objective: To investigate the clinical relevance of endometriosis-associated nerve fibers in the development of
endometriosis-associated symptoms.
Design: Prospective nonrandomized study.
Setting: University hospital endometriosis center.
Patient(s): Fifty-one premenopausal patients underwent surgical laparoscopy because of chronic pelvic pain, dysmenorrhea,
or for ovarian cysts. Endometriosis was diagnosed in 44 patients.
Intervention(s): The preoperative and postoperative pain scores were determined using a standardized questionnaire
with a visual analogue scale from 1–10. Patients with peritoneal endometriosis were divided into two groups
depending on their preoperative pain score: group Awith a pain score of at least 3 or more and group B with a pain
score of 2 or less. Patients without peritoneal endometriosis were classified as group C and patients without endometriosis
were classified as group D. Immunohistochemical analysis of neurofilament and protein gene product 9.5
were used for nerve fiber detection. Occurrence of endometriosis-associated nerve fibers was correlated with the
severity of pelvic pain and/or dysmenorrhea.
Result(s): Peritoneal endometriosis-associated nerve fibers were found significantly more frequently in group A
than in group B (82.6% vs. 33.3%).
Conclusion(s): The present study suggests that the presence of endometriosis-associated nerve fibers in the peritoneum
is important for the development of endometriosis-associated pelvic pain and dysmenorrhea
Sylvia Mechsner, 2009

39. Nerve fibres in ovarian endometriotic lesions in women with ovarian endometriosis
Histological sections of ovarian endometriotic lesions from 61 women with ovarian endometriosis (Stages II–IV) who underwent laparoscopic endometrioma
Nerve fibres stained with PGP9.5 were detected in ovarian endometriotic lesions in 31.1% of women, and most appeared in fibrotic interstitium of ovarian endometriotic lesions. The density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions in women with pain symptoms (n 35) was higher than in women with no pain symptoms (n 26, P ), although the percentage (positive cases/total) of PGP9.5-positive fibres did not differ cystectomy
background: Although nerve fibres are present in eutopic and ectopic endometrium, it is unclear whether they appear in ovarian
endometriotic lesions. We investigated the presence of nerve fibres in ovarian endometriotic lesions and its correlation with clinical parameters
in women with ovarian endometriosis.
methods: Histological sections of ovarian endometriotic lesions from 61 women with ovarian endometriosis (Stages II–IV) who underwent
laparoscopic endometrioma cystectomy were stained immunohistochemically using a specific polyclonal rabbit anti-protein gene
product 9.5 (PGP9.5) antibody to demonstrate myelinated and unmyelinated nerve fibres.
results: Nerve fibres stained with PGP9.5 were detected in ovarian endometriotic lesions in 31.1% of women, and most appeared in
fibrotic interstitium of ovarian endometriotic lesions. The density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions in women
with pain symptoms (n ¼ 35) was higher than in women with no pain symptoms (n ¼ 26, P ¼ 0.039), although the percentage (positive
cases/total) of PGP9.5-positive fibres did not differ. In women with pain symptoms, PGP9.5-positive fibres appeared in 40.0% of cases
and the density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions was correlated with severity of pain symptoms (r ¼
0.466, P ¼ 0.005). In women with no pain, PGP9.5-positive fibres were detected in only 5 (19.2%) women. Both the percentage and the
density of PGP9.5-positive fibres in ovarian endometriotic lesions were associated with pelvic adhesions (x2 ¼ 6.833, P ¼ 0.009; Z ¼
2.442, P ¼ 0.015, respectively) but not with disease severity.
conclusions: PGP9.5-immunoactive nerve fibres in ovarian endometriotic lesions may be involved in the pathophysiology of pain generation
and pelvic adhesion formation in women with ovarian endometriosis.
Xinmei Zhang, 2010

40. Effect of progestogens and combined oral contraceptives on nerve fibers in peritoneal endometriosis
Biopsy samples from peritoneal endometriotic lesions in hormonally treated and untreated women with endometriosis. (N: 22 vs. N:40)
The nerve fiber density (mean standard deviation/mm2) in peritoneal endometriotic lesions from hormone-treated women with endometriosis ( /mm2) was statistically significantly lower than in peritoneal endometriotic lesions from untreated women with endometriosis ( /mm2).
Progestogens and combined oral contraceptives reduced nerve fiber density and nerve growth factor and nerve growth factor receptor p75 expression in peritoneal endometriotic lesions.
To investigate how progestogens and combined oral contraceptives change nerve fiber density in peritoneal
endometriotic lesions and to identify the types of nerve fibers still present during hormone treatment.
Design: Laboratory study using human tissue.
Setting: University-based laboratory.
Patient(s): Hormonally treated and untreated women with endometriosis undergoing laparoscopy, hysteroscopy,
and curettage.
Intervention(s): Biopsy samples from peritoneal endometriotic lesions in hormonally treated and untreated
women with endometriosis.
Main Outcome Measure(s): Types and density of nerve fibers were immunohistochemically determined in peritoneal
endometriotic lesions from hormonally treated and untreated women with endometriosis.
Result(s): The nerve fiber density (mean standard deviation/mm2) in peritoneal endometriotic lesions from hormone-
treated women with endometriosis ( /mm2) was statistically significantly lower than in peritoneal
endometriotic lesions from untreated women with endometriosis ( /mm2). Nerve growth factor and
nerve growth factor receptor p75 expression in peritoneal endometriotic lesions were slightly reduced in hormone-
treated women with endometriosis compared with untreated women with endometriosis.
Conclusion(s): Progestogens and combined oral contraceptives reduced nerve fiber density and nerve growth factor
and nerve growth factor receptor p75 expression in peritoneal endometriotic lesions.
Natsuko Tokushige, 2009

41. Endometrial nerve fibers in women with endometriosis, adenomyosis, and uterine fibroids
To determine whether nerve fibers in the functional layer endometrium are caused by an endometriosis itself or a common symptom of pain, endometrial tissues from 30 women with endometriosis, 40 women with adenomyosis, 41 women with uterine fibroids, and 47 endometriosis women with adenomyosis were stained immunohistochemically using the highly specific polyclonal rabbit antiprotein gene product 9.5 (PGP9.5) and monoclonal mouse antineurofilament protein.
We demonstrated PGP9.5-immunoactive nerve fibers in the functional layer of endometrium in women with pain symptoms, but not in women without pain symptoms, whether the women had endometriosis, adenomyosis, uterine fibroids, or endometriosis with adenomyosis, suggesting a role of PGP9.5-immunoactive nerve fibers in the functional layer of the endometrium playing in pain generation in these disorders
To determine whether nerve fibers in the functional layer endometrium are caused by an endometriosis itself or
a common symptom of pain, endometrial tissues from 30 women with endometriosis, 40 women with adenomyosis,
41 women with uterine fibroids, and 47 endometriosis women with adenomyosis were stained immunohistochemically
using the highly specific polyclonal rabbit antiprotein gene product 9.5 (PGP9.5) and monoclonal
mouse antineurofilament protein. We demonstrated PGP9.5-immunoactive nerve fibers in the functional layer
of endometrium in women with pain symptoms, but not in women without pain symptoms, whether the women
had endometriosis, adenomyosis, uterine fibroids, or endometriosis with adenomyosis, suggesting a role of
PGP9.5-immunoactive nerve fibers in the functional layer of the endometrium playing in pain generation in these
disorders. (
Xinmei Zhang, 2009

42. Diagnostic accuracy of transvaginal sonography for the diagnosis of adenomyosis: systematic review and metaanalysis
OBJECTIVE: The purpose of this study was to critically appraise the
diagnostic accuracy of transvaginal sonography for diagnosing
adenomyosis.
STUDY DESIGN: Computerized databases were used to identify relevant
reports published between 1966 and 2007 reporting data on
the accuracy of transvaginal sonography for diagnosing adenomyosis
in women having hysterectomy. The presence or absence of
adenomyosis was confirmed by histopathologic analysis of hysterectomy
specimens. The total analysis included 14 trials with 1895
aggregate participants. Two authors independently assessed methodological
quality and constructed tables for the assessment of diagnostic
measures.
RESULTS: Transvaginal ultrasound predicted adenomyosis with a likelihood
ratio of 4.67 (95% confidence interval [CI], ). The
overall prevalence of adenomyosis was 27.9% (95% CI, ).
The probability of adenomyosis with an abnormal transvaginal ultrasound
was 66.2% (95% CI, ). The probability of adenomyosis
with a normal transvaginal ultrasound was 9.1% (95% CI, ).
CONCLUSION: Transvaginal sonography appears to be an accurate diagnostic
test for adenomyosis
Susanna M. Meredith, 2009

43. 2009
OBJECTIVE: To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception. DESIGN: Prospective data collection on 579 patients and comprehensive statistical analysis to derive a new staging system-the endometriosis fertility index (EFI)-from data rather than a priori assumptions, followed by testing the EFI prospectively on 222 additional patients for correlation of predicted and actual outcomes. SETTING: Private reproductive endocrinology practice. PATIENT(S): A total of 801 consecutively diagnosed and treated infertile patients with endometriosis. INTERVENTION(S): Surgical diagnosis and treatment followed by non-IVF fertility management. MAIN OUTCOME MEASURE(S): The EFI and life table PRs. RESULT(S): A statistically significant variable used to create the EFI was the least function score (i.e., the sum of those scores determined intraoperatively after surgical intervention that describe the function of the tube, fimbria, and ovary on both sides). Sensitivity analysis showed that the EFI varies little, even with variation in the assignment of functional scores, and predicted PRs. CONCLUSION(S): The EFI is a simple, robust, and validated clinical tool that predicts PRs after endometriosis surgical staging. Its use provides reassurance to those patients with good prognoses and avoids wasted time and treatment for those with poor prognoses
To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception.

45. Decreased anti-Mullerian hormone and altered ovarian follicular cohort in infertile patients with mild/minimal endometriosis
p:0.004
N:17
N:17 EE CC
Objective: To evaluate the ovarian reserve and follicular cohort of infertile patients with minimal/mild endometriosis.
Design: Prospective study.
Setting: University hospital.
Patient(s): Patients were divided into two groups: group I, minimal/mild endometriosis and group II, tubal obstruction.
The following exclusion criteria were established: [1] patients with previous endocrine disorders; and
[2] cases in which the cause for infertility was other than endometriosis (except for patients with tubal obstruction,
in the control group).
Intervention(s): Serum FSH and anti-M€ullerian hormone were measured on day 3. On the same day all patients
were submitted to transvaginal ultrasound to evaluate the antral follicular count and the ovarian follicular cohort.
Main Outcome Measure(s): Serum FSH, anti-M€ullerian hormone, and the follicular cohort with the respective
antral follicular count.
Result(s): Serum FSH were not different between the groups. However, infertile patients with endometriosis have
a decreased serum anti-Mullerian hormone ( ng/mL) compared to the control group ( ng/mL).
The analysis of follicular cohort showed that the number of selectable follicles were similar, but the follicular
diameter was different.
Conclusion(s): Minimal/mild endometriosis is associated with a decrease in the follicular ovarian reserve. In addition,
the follicular cohort of these patients is more heterogeneous in comparison to the control group.
Nadiane Albuquerque Lemos, 2009

46. Anti mullerian hormone serum levels in women with endometriosis: A case–control study
909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment or consulting our specific endometriosis unit.
Mean AMH serum level was significantly lower in the study than in the control group ( ng/ml vs ng/ml, p 0.001).
In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the control group ( ng/ml vs ng/ml; p 0.61).
A significant difference in mean AMH serum level was found between women with severe endometriosis (rAFS III-IV) and the control group ( ng/ml vs ng/ml; p ).
Objective. To compare the anti muellerian hormone (AMH) serum levels in women with and without endometriosis.
Design. A case–control study
Setting. Women’s General Hospital, Linz, Austria.
Patient(s). Our study included a total of 909 patients undergoing in vitro fertilisation/intracytoplasmic sperm injection
(IVF/ICSI) treatment or consulting our specific endometriosis unit. After proofing the exclusion criteria, 153 of these
patients with endometriosis (study group) were matched with 306 patients undergoing IVF/ICSI treatment because of a male
factor (control group).
Interventions. None.
Main outcome measures. AMH serum level.
Results. Mean AMH serum level was significantly lower in the study than in the control group ( ng/ml vs.
ng/ml, p50.001). In women with mild endometriosis (rAFS I-II), the mean AMH level was almost equal to the
control group ( ng/ml vs ng/ml; p¼0.61). A significant difference in mean AMH serum level was
found between women with severe endometriosis (rAFS III-IV) and the control group ( ng/ml vs.
ng/ml; p ).
Conclusion. Lower AMH serum levels and an association with the severity were found in women with endometriosis.
Physicians have to be aware of this fact. Because of the expected lower response on a controlled ovarian hyperstimulation
(COH), AMH serum level should be measured to optimise the dose of gonadotropin treatment previous to a COH,
especially in women with severe endometriosis.
OMAR SHEBL, 2009

47. Effects of ovarian endometrioma on the number of oocytes retrieved for in vitro fertilization
Objective: To evaluate the effects of ovarian endometrioma on the number of oocytes retrieved for IVF.
Setting: University-based tertiary medical center.
Patient(s): We studied 81 women with unilateral endometrioma who underwent their first IVF cycle.
Intervention(s): Oocyte collection.
Main Outcome Measure(s): The numbers of antral follicles and the retrieved oocytes in the ovary that contained
endometrioma were compared with those from the contralateral ovary. Antral follicle count and the total number of
oocytes retrieved from these women then were compared with those in 162 age-matched women with no endometrioma
or endometriosis, who also underwent the first IVF treatment cycle.
Result(s): There was no significant difference in the number of antral follicles and oocytes retrieved in the
endometrioma-containing ovary ( and , respectively) and in the opposite ovary ( and
8.50.9, respectively). There was no correlation between the size and the number of endometriomas with the number
of retrieved oocytes. Antral follicle count and the number of retrieved oocytes in these women ( and
) were similar to those in women with no endometrioma ( and , respectively).
Conclusion(s): The presence of ovarian endometrioma in a controlled ovarian hyperstimulation cycle for IVF
treatment is not associated with a reduced number of oocytes retrieved from the affected ovary
Benny Almog, 2010

48. The impact of electrocoagulation on ovarian reserve after laparoscopic excision of ovarian cysts: a prospective clinical study of 191 patients
191 patients with benign ovarian cysts undergoing ovarian cystectomy.
When comparing the bipolar group and ultrasonic scalpel group with the suture group, a statistically significant increase of the mean FSH value was found in bilateral-cyst patients at 1-, 3-, 6-, and 12-month follow-up evaluations and in unilateral-cyst patients at the 1-month follow-up evaluation.
Statistically significant decreases of basal antral follicle number and mean ovarian diameter were found during the 3-, 6-, 12-month follow-up evaluations as well as statistically significant decreases of peak systolic velocity at all of the follow-up evaluations.
Conclusion(s): Electrocoagulation after laparoscopic excision of ovarian cysts is associated with a statistically significant reduction in ovarian reserve, which is partly a consequence of the damage to the ovarian vascular system.
Objective: To investigate the impact of electrocoagulation on ovarian reserve after laparoscopic excision of ovarian
cysts and the possible mechanisms.
Design: A prospective study.
Setting: Obstetrics and Gynecology Department of a university hospital.
Patient(s): 191 patients with benign ovarian cysts undergoing ovarian cystectomy.
Intervention(s): Laparoscopic ovarian cystectomy using bipolar or ultrasonic scalpel electrocoagulation and laparotomic
ovarian cystectomy using sutures after the excision of ovarian cysts.
Main Outcome Measure(s): Follicle-stimulating hormone (FSH) assay and transvaginal ultrasound evaluating
basal antral follicle number, mean ovarian diameter, and ovarian stromal blood flow velocity at day 3 of menstrual
cycles 1, 3, 6, and 12 after surgery.
Result(s): When comparing the bipolar group and ultrasonic scalpel group with the suture group, a statistically
significant increase of the mean FSH value was found in bilateral-cyst patients at 1-, 3-, 6-, and 12-month follow-
up evaluations and in unilateral-cyst patients at the 1-month follow-up evaluation. Statistically significant decreases
of basal antral follicle number and mean ovarian diameter were found during the 3-, 6-, 12-month follow-up
evaluations as well as statistically significant decreases of peak systolic velocity at all of the follow-up evaluations.
Conclusion(s): Electrocoagulation after laparoscopic excision of ovarian cysts is associated with a statistically significant
reduction in ovarian reserve, which is partly a consequence of the damage to the ovarian vascular system
Chang-Zhong Li, 2009

49. A comparison of histopathologic findings of ovarian tissue inadvertently excised with endometrioma and other kinds of benign ovarian cyst in patients undergoing laparoscopy versus laparotomy
Objective: To evaluate ovarian tissue inadvertently excised with benign cysts during laparotomy or laparoscopy.
Design: Prospective study.
Setting: Private and university hospitals.
Patient(s): 260 women, 20 to 35 years old, with unilateral benign ovarian cysts.
Intervention(s): One hundred fifty women operated by laparoscopic cystectomy stripping technique, and 110
women operated by laparotomy with the same technique.
Main Outcome Measure(s): Histopathologic findings of ovarian tissue inadvertently excised in endometrioma
compared with other kinds of benign cysts in laparoscopy versus laparotomy.
Result(s): In the laparoscopy group, ovarian tissue was present in 65% of endometrioma and in 32% of nonendometriotic
cysts. In the laparotomy group, ovarian tissue was seen in 80% of endometrioma and 41% of nonendometriotic
cysts.
Conclusion(s): The surgical approach had no statistically significant impact on conservation of ovarian reserves.
The nature of the ovarian cyst played a greater role in the quality and quantity of the excised ovarian tissue
Saeed Alborzi, 2009

50. Analysis of risk factors for the removal of normal ovarian tissue during laparoscopic cystectomy for ovarian endometriosis
A total of 121 patients who had histologically confirmed ovarian endometriosis and 56 control patients who had other histologically confirmed benign cysts were included
Normal ovarian tissue adjacent to the cyst wall was detected in 71 patients (58.7%) with endometriosis, whereas normal ovarian tissue was removed from only three patients (5.4%) with other benign cysts.
A significant factor that was independently associated with the removal of normal ovarian tissue with ovarian endometriosis was pre-operative medical treatment
background: The aim of this study was to identify risk factors for the removal of normal ovarian tissue during laparoscopic cystectomy
for endometriosis.
methods: A total of 121 patients who had histologically confirmed ovarian endometriosis and 56 control patients who had other histologically
confirmed benign cysts were included for the present analysis. The blocks of removed tissue were sectioned at 120 mm intervals
and a total of five sections were analyzed for each ovarian cyst. Eight variables (age, pre-operative medical treatment, previous surgery for
ovarian endometriosis, single or multiple cysts, size of the largest cyst, side of cyst, co-existence of deep endometriosis, revised American
Society for Reproductive Medicine classification) were evaluated using a generalized linear modeling analysis to identify major factors associated
with the removal of normal ovarian tissue.
results: Normal ovarian tissue adjacent to the cyst wall was detected in 71 patients (58.7%) with endometriosis, whereas normal
ovarian tissue was removed from only three patients (5.4%) with other benign cysts. A significant factor that was independently associated
with the removal of normal ovarian tissue with ovarian endometriosis was pre-operative medical treatment.
conclusions: The present retrospective, controlled study suggests that pre-operative medical treatment might be a risk factor for the
removal of normal ovarian tissue during laparoscopic cystectomy for ovarian endometriosis.
Sachiko Matsuzaki1,2009

51. Endometriosis/Endometrioma-ART
Does Endometriosis/endometrioma affect the ovarian reserve ?
Yes, but pregnancy rates do not change
Does Endometriosis/endometrioma surgery affect the ovarian reserve ?
Yes
Spontan pregnancy rates may increase, but Ivf results do not change (except bilateral cases)

53. Results of studies comparing IVF-ET with second-line surgery in infertile women with recurrent moderate to severe endometriosis
P. Vercellini , 2009

54. SART-2007

55. IVF-ICSI outcome in women operated on for bilateral endometriomas.
68 cases (bilat. cystectomy)- 136 controls
the number of follicles (P = 0.006), oocytes retrieved
(P = 0.024) and embryos obtained (P = 0.024) were significantly lower.
The clinical pregnancy rate per started cycle in cases and controls was 7% and 19% (P = 0.037)
CONCLUSIONS: IVF outcome is significantly impaired in women operated on for bilateral ovarian endometriomas.
BACKGROUND: The influence of previous conservative surgery for endometriomas on IVF–ICSI outcome is
debated. Conflicting information emerging from the literature may be consequent to the fact that endometriomas
are mostly monolateral. The contralateral intact ovary may adequately supply for the reduced function of the affected
one. To clarify this point, we assess IVF–ICSI outcome in women operated on for bilateral endometriomas.
METHODS: Women selected for IVF–ICSI cycles who previously underwent bilateral endometriomas cystectomy
were matched (1:2) for age and study period with patients who did not undergo prior ovarian surgery. RESULTS:
Sixty-eight cases and 136 controls were recruited. Women operated on for bilateral endometriotic ovarian cysts
had a higher withdrawal rate for poor response (P < 0.001). In these patients, despite the use of higher doses of gonadotrophins,
the number of follicles (P ), oocytes retrieved (P ) and embryos obtained (P ) were
significantly lower. The clinical pregnancy rate per started cycle in cases and controls was 7% and 19% (P )
and the delivery rate per started cycle was 4% and 17%, respectively (P ). CONCLUSIONS: IVF outcome is
significantly impaired in women operated on for bilateral ovarian endometriomas.
Edgardo Somigliana1, 2008

56. Endometriomas and IVF- Meta Analysis
Tsoumpou et al. Fertil Steril 2008

58. Endometrioma and IVF
GPP
Laparoscopic ovarian cystectomy is recommended if an
ovarian endometrioma ≥4 cm in diameter is present to confirm the diagnosis histologically; reduce the risk of infection; improve access to follicles and possibly improve ovarian response.
The woman should be counselled regarding the risks of reduced ovarian function after surgery and the loss of the ovary.
The decision should be reconsidered if she has had previous ovarian surgery.
30 June 2007

59. Surgery pre ART Infertility ART Sx ovarian suppression IVF / ICSI
Work up
ART 1
Ovarian reserve
Time available for in vivo 1
Emergency
I V F 2
Semen analysis 2
IVF for severe
male factor 3
Fallopian tubes 3
IVF for
tubal factor Sx
Surgery
in principle
NO surgery
Provide 6-18 mo
for spontaneous preg.
ovarian suppression
(3 months)
IVF / ICSI
if not pregnant

60. Cryopreservation of oocytes in a young woman with severe and symptomatic endometriosis: a new indication for fertility preservation.
2009
25 y, symptomatic endometriosis, one ovary, low AFC, 3 Cycles, 21 Oocytes
OBJECTIVE: To report a new indication for fertility preservation. DESIGN: Case report. SETTING: Academic teaching hospital. PATIENT(S): A 25-year-old nulliparous woman with severe and symptomatic endometriosis and low antral follicular count. INTERVENTION(S): Oocyte cryopreservation. MAIN OUTCOME MEASURE(S): Number of cryopreserved oocytes. RESULT(S): After three cycles of ovarian stimulation, we cryopreserved 21 oocytes. CONCLUSION(S): We recommend fertility preservation as part of preoperative counseling in young women with severe endometriosis.

62. 2008

66. Endometriosis-GnRHa Pain After operation for the prevention Before IVF
Empirical

67. Sallam, Garcia-Velasco, Dias, and A Arici, Cochrane Database 2006
GnRH agonist vs. no agonist before IVF (Clinical pregnancy rate per woman)
Sallam, Garcia-Velasco, Dias, and A Arici, Cochrane Database 2006

68. ACOG 2004

70. Gonadotropin-releasing hormone agonist and add-back therapy: what do the data show?
Regardless of the regimen employed, it has been consistently demonstrated that effective add-back therapy should be initiated concomitantly with the GnRHa to
minimize side effects.
However, for the woman who
requires retreatment with a GnRHa or whose therapy is anticipated to extend beyond 6 months, add-back should be considered mandatory
Eric S. Surrey, 2010

71. Deep endometriosis: Excisional surgery Pregnancy rates
Vercellini et al.,
Hum Reprod (2009)

72. Deep endometrisois: Complications
Vercellini et al.,
Hum Reprod (2009)

73. BACKGROUND Although surgery is currently the treatment of choice for managing endometriosis, recurrence poses a formidable challenge. To delay or to eliminate the recurrence is presently an unmet medical need in the management of endometriosis. To this end, proposals to investigate patterns of recurrence, to develop biomarkers for recurrence and to carry out biomarker-based intervention have been made. METHODS Publications pertaining to the recurrence of endometriosis and its related yet unaddressed issues were identified through MEDLINE. The reported recurrence rates, risk factors for recurrence, the effects of post-operative medication and causes of recurrence were reviewed and synthesized. In addition, several poorly explored issues such as time hazard function and mechanisms of recurrence were reviewed. Approaches to the development of biomarkers for recurrence and future intervention are discussed. RESULTS The reported recurrence rate was high, estimated as 21.5% at 2 years and 40-50% at 5 years. Few risk factors for recurrence have been consistently identified, and the evidence on the efficacy of the post-operative use of medication was scanty. The investigation on the patterns of recurrence may provide us with new insight into the possible mechanisms of recurrence and its control. The attempt to identify biomarkers for recurrence has started only very recently. CONCLUSIONS Much research is needed to better understand the patterns of recurrence and risk factors, and to develop biomarkers. One top priority is to develop biomarkers for recurrence, which may provide much needed clues to the possible mechanisms underlying recurrence and would allow the identification of patients with high recurrence risk, and permit for targeted intervention.
The reported recurrence rate was high, estimated as 21.5% at 2 years and 40-50% at 5 years.

76. Endometriosis – Higher Prevalence for
Ovarian Cancer
Review of an ovarian endometrioma cohort (6398)
follow up of 17 years: 46 ovarian cancers
Standardized Incidence Ratio (SIR) 8.95
Independent predictors: age > 40 years
endometrioma size > 9 cm
slightly elevated CA-125
Kobayashi 2009, Int J Clin Oncol; 14:
Ovarian cancer in endometriosis: epidemiology, natural history, and clinical diagnosis

77. Endometrioid and Clear Cell Ovarian Cancers – Risk Factors
Decreased risk: - Increasing parity
- OC for => 5 years
- breast feeding
- tubal ligation
Increased risk: - endometriosis OR 2.2 endometrioid
OR 3.0 clear cell
Nagle et al., Eur J Cancer; 44:
Endometrioid and clear cell ovarian cancers: a comparative analysis of risk factors

78. The Centre/Network of Excellence in Endometriosis
Gynaecological
General
Bowel
Bladder
Lung
IVF
ICSI
IUI
Surgeons
Reproductive endocrinologists
WOMAN
and
GYNAECOLOGIST
the decision making team
Immunologists
Nutritionists
Psychologists/counsellors
Pain management
Physiotherapy
Massage
Acupuncture
Stress mgmt
Exercise
Nurses
Telephone
Online
Meetings
Literature
Onsite support
TCM
Homeopathy
Reflexology
Herbalists
Patient support groups
Complementary therapies
D'Hooghe and Hummelshoj, Hum Reprod 2006