Endometriosis Guideline

Clinical Guidelines for the
Clinical Guidelines for the Management of Endometriosis
Management of
Contents
Endometriosis
2016
Endorsed by
Contents
Guidelines development group i

1.0 Introduction 1
What is endometriosis 1
Why is it important? 1
Purpose of this proposed guideline 1
2.0 Endometriosis 2
2.1 The basic science of endometriosis 2
3.0 Diagnosis – Laparoscopy versus clinical 5
3.1 Classifications 8
3.1.1 The revised American Society for Reproductive Medicine score 8
3.1.2 The ENZIAN Staging System 8
4.0 Treatment options for Pain 9
4.1 Laparoscopy before commencement of treatment 9
4.2 Medical treatment 10
4.2.1 Combined estrogen and progestin therapy 11
4.2.2 Oral progestin therapy 12
4.2.3 Depot progestin therapy 13
4.2.4 Interuterine progestin-releasing system 13
4.2.5 Danazol 13
4.2.6 GnRH agonists 14
4.2.7 Aromatase inhibitors (AI) 14
4.2.8 Analgesia 15
4.3 Surgical management of endometriosis 17
4.3.1 Indications 17
4.3.2 Preoperative evaluation 19
4.3.3 Surgical approach 19
4.3.4 Deeply Infiltrating Endometriosis (DIE) 19
4.3.5 Ovarian Endometriosis 20
4.3.6 Additional surgical interventions 21
Contents
5.0 Fertility Issues 21

5.1 Diagnosis 21
5.2 Medical therapy 23
5.3 Surgical treatment 24
5.3.1 Indications for surgery 24
5.3.2 Laparotomy versus laparoscopy 25
5.3.3 Surgical principles, procedures and techniques 25
5.3.4 Recurrent surgery 26
5.4 Options after surgery 27
5.5 Assisted reproduction 28
5.5.1 Super-ovulation and intrauterine insemination (SO/IUI) 28
5.5.2 In vitro fertilisation (IVF) 28
6.0 Post-menopausal management of endometriosis 29
6.2 Pathogenesis of post-menopausal endometriosis 29
6.3 Treatment options of post-menopausal endometriosis 29
7.0 Endometriosis and the risk of cancer 30
7.1 Epidemiology 30
7.2 Pathophysiology 31
7.3 Management 32
Appendix 33
American Society of Reproductive Medicine Score 33
Enzian Staging System 36
Notes 37
Guidelines development
Clinical Guidelines to the Managementgroup
of Endometriosis
Chairperson
Dr Raman Subramaniam
MBBS, MD, FRCOG, FRCPI, FACS
Consultant Obstetrician and Gynaecologist
Members (in alphabetical order)

Dr Eeson Sinthamoney
MD, FRCOG, DFFP
Fellowship in Reproductive Medicine
and Fertility Specialist
Dr Premitha Damodaran
MBBS, MMed
Dr Suresh Kumarasamy
MBBS, MObGyn, FRCOG, FRCPI, AM
and Gynaecological Oncologist
Dr Tham Seong Wai

MBBS, MMed
i
1.0 Introduction
Clinical Guidelines to the Management of Endometriosis
What is endometriosis
Endometriosis is a common but debilitating disease that affects between 5 –
10% of women of reproductive age.1 Clinically, endometriosis is defined as the
presence of endometrial glands and stromal tissue outside the uterus. This
causes an estrogen-dependent chronic inflammatory process which results
in substantial morbidity, severe pelvic pain, multiple surgeries and impaired
fertility 2,3
At present, there is no consensus on what is the cause of this disease. Healthcare

professionals need to be aware that there are a number of possible factors that
would increase the chances an individual would suffer from endometriosis.
Studies have indicated that genetics may increase the risk of endometriosis
by 3 to 10 times, particularly among first-degree relatives of women with
endometriosis.2
Why is it important?
Endometriosis is not merely a disease that affects the reproductive system of a
woman. Studies have shown that regardless of age, endometriosis negatively
affects a woman’s life in terms of marital/sexual relationships, social life,
physically and psychologically.3
Purpose of this proposed guideline

The purpose of this guideline is to provide healthcare providers with practical
advice on the care of women with endometriosis. This guideline will highlight
diagnosis, classification, and treatment for endometriosis-related pain and
infertility. This guideline serves to address the limitations that are faced in the
treatment of this condition in Malaysia. The areas that we need to address are
the expertise in advanced laparoscopy as well as the availability of assisted
reproductive techniques in Malaysia.
For further reading and levels of evidence, kindly refer to the 2014 European Society of
Human Reproduction and Embryology (ESHRE) Guidelines: Management of women with
endometriosis.
References:
1. Walker KG, et al. Eur J Obstet Gynecol Reprod Biol. 1993;48:135–139.
2. Wheeler JM. Infertil Reprod Med Clin North Am. 1992;3:545–549.
3. Moradi M, et al. BMC Womens Health. 2014;14:123.
1
2.0 Endometriosis
2.1 The basic science of endometriosis

At present, the pathogenesis of endometriosis is still unclear. However, there
are several theories behind the cause of this disease.
On a cellular level, the failure of immune mechanisms to destroy ectopic

tissue and prevent abnormal differentiation of endometriotic tissue has been
suggested to be the cause of the stromal-cell defects associated with the
increased estrogen and prostaglandin production, along with resistance to
progesterone.1
The failure of immune mechanisms to destroy ectopic tissue and prevent

abnormal differentiation of endometriotic tissue has been suggested as the
cause of stromal-cells defects.
The theory of retrograde menstruation, whereby the menstrual tissue refluxes

into the fallopian tubes and implants on the pelvic structures has been credited
to Dr Sampson.2 However, retrograde menstruation occurs in most women but
the disease only occurs in 10 – 15% of women.
Increased estrogen sensitivity along with an increase in progesterone

resistance have been found in women with endometriosis. Endometriotic
lesions may also develop when coelomic mesothelial cells of the peritoneum
undergo metaplasia. There are also theories that postulate the circulation and
implantation of ectopic menstrual tissue via the venous or lymphatic system,
or both.3
Endometriotic cell survival and growth and associated inflammation are

responsible for the clinical symptoms of infertility and pain. Inflammation, the
main feature of endometriotic lesions, is characterised by the overproduction of
cytokines, prostaglandins, and other inflammatory substances that cause pain
and is associated with infertility. Additionally, estrogen promotes the survival
and persistence of endometrial lesions.3
Key message:
Clinicians need to be aware of the various factors that increase
the likelihood of endometriosis.
2
2.0 Endometriosis
Types of endometriosis
There are several types of endometriosis:
Peritoneal endometriosis: Peritoneal implants that consist of glandular

and stromal tissue and respond to hormonal changes associated with the
menstrual cycle showing cyclic changes similar but not identical to the normal
endometrium. These implants heal by fibrosis.4
Ovarian endometriomas: Benign, estrogen-dependent cyst also known as

“chocolate cyst” that contains thick, old blood that appears as a brown fluid.5
This results from recurrent chronic bleeding from the endometriotic implants.
In long-standing endometriomas, the endometriotic tissue is gradually replaced
by fibrotic tissue.4
Deep endometriosis (DE): This form of endometriosis is characterised

by proliferative fibromuscular tissue with sparse endometrial grandular and
stromal tissue (akin to adenomyosis), with no surface epithelium. DE does not
show significant changes during the menstrual cycle. Growth of endometriotic
nodules are usually found in the uterosacral ligaments, the rectovaginal space,
the upper third of the posterior vaginal wall, the bowel, and the urinary tract.4,6
Adenomyosis: Uterine endometriosis presents as asymmetrical uterine

enlargement.
Disseminated endometriosis: Growth of endometriotic tissue in various

organs in the body including at the scar site.
3
2.0 Endometriosis
Clinical manifestations
Box 2.1: Common presenting symptoms for endometriosis4,7
Pain in endometriosis presents as any of the following:

• Painful menstruation (dysmenorrhoea)
• Painful intercourse (dyspareunia)
• Painful defecation (dyschezia) that may be cyclic or semi-cyclic.
• Painful micturition (dysuria)
• Lower back or abdominal discomfort
• Chronic pelvic pain (non-cyclic abdominal pelvic pain of at least 6
months duration)
Atypical presentations include cyclic leg pain or sciatica (nerve involvement),

cyclic rectal bleeding or haematuria (bowel or bladder invasion), and cyclic
dyspnoea secondary to catamenial pneumothorax. These presentations are
indicative of a more significant disease involvement.3
Physical examinations may present with the following3:

• Painful induration and/or nodules of the rectovaginal wall or visible vaginal
nodules in the posterior vaginal fornix (DE)
• Detection of adnexal masses (ovarian endometrioma)
• Fixed, retroverted uterus (severe adhesive disease).
Complications
Endometriosis can be a cause of subfertility and pain. Epidemiological
and laboratory evidence have linked endometriosis with epithelial ovarian
carcinoma.
Key message:
The primary focus of investigation and treatment of
endometriosis should be the resolution of presenting symptoms.
References:
1. Bulun SE. NEJM. 2009;360:268–279.
2. Sampson JA. Am J Obstet Gynecol. 1927;14:22–69.
3. Leyland N, et al. J Obstet Gynaecol Can. 2010;32(7 Suppl 2):S1–S32.
4. Raffi F. JPOG. 2012;38(3):93–104.
5. Carnahan M, et al. Expert Rev Obstet Gynecol. 2013;8(1):29–55.
6. Chapron C, et al. Hum Reprod. 2006;21:1839–1845.
7. Millburn A, et al. Obstet Gynecol Clin North Am. 1993;20:643–661.
4
3.0 Diagnosis – Laparoscopy versus clinical
Figure 1: Diagnostic pathway1*
Clinical presentation:
typical symptoms
Endometriosis suspected
History Examination
Investigations
Consider differential
diagnoses
Provisional diagnosis
of endometriosis –
Management
considerations
*adapted from the SOGC Guidelines
Generally, diagnosis of endometriosis is based on the history, the

symptoms and signs, physical examination and imaging techniques.
Physical examinations should include an assessment to determine the
position, size, and mobility of the uterus. Rectovaginal examinations are
useful in determining presence of DE. Other than the examination of the
pelvic region, inspection and palpation of the abdomen is also advised.2
Key message:
When deeply infiltrating endometriosis is suspected, a
pelvic examination, including rectovaginal examination, is
essential.
5
Ultrasonography is the first-line investigational tool for suspected endometriosis.

It allows detection of ovarian cysts and other pelvic disorders such as uterine
fibroids. There is little support for the routine use of blood works, or other
imaging studies in the primary investigation of these cases.1
The serum level of cancer antigen 125 (CA-125) may be elevated in some cases
of endometriosis. However, there is no value of CA-125 in diagnosis or follow-up.
However, if the appearance of the ovarian cyst is suggestive of an origin other
than endometriosis, CA-125 and other tumour markers are recommended.3
It has been traditionally believed that laparoscopy must be performed to definitely

diagnose endometriosis. Direct visualisation with laparoscopy and histology has
been regarded as the gold standard for diagnosis. However, this view has been
recently challenged as nonsurgical diagnosis of endometriosis have proven to be
highly reliable.4
Diagnostic laparoscopy should be done by an experienced laparoscopic

surgeon and preceded by appropriate preoperative assessment.5 The severity
of endometriosis is best described by the appearance and location of the
endometriotic lesions and the involvement of any organs.1
Diagnostic laparoscopy is not required before treatment of all patients with

pelvic pain. Despite being considered a minimally invasive procedure, there are
still surgical risks including bowel and bladder perforation and vascular injury.
The overall risk of any complication with laparoscopy, minor or major, varies
with publications and in this reference, is 8.9%.6 Diagnostic laparoscopy carries
a lower risk than operative laparoscopy.7
6
When endometriosis is thought to be of the DE variety, ancillary tests such as

colonoscopy, cystoscopy, rectal ultrasonography, and MRI may be required.1,2
Key messages:
1. Investigation of the suspected endometriosis should include
history, physical examination and imaging assessments.
2. The role of CA-125 in the diagnosis and follow-up of
endometriosis has not been shown to have any proven value.
3. The role of laparoscopy for the definitive diagnosis of
endometriosis is not thought to be essential in all cases.
References:
2. Dunselman GAJ, et al. Hum Reprod. 2014;29(3):400–412.
3. Bedaiwy MA and Falcone T. Clin Chim Acta. 2004;340(1 – 2):41–56.
4. Vercellini P, et al. Best Pract Res Clin Obstet Gynaecol. 2008;22(2):275–306.
5. Wykes CB, et al. BJOG. 2004;111:1204–1212.
7. Royal College of Obstetricians and Gynaecologists (RCOG). RCOG Guideline No. 27. (2006).
7
3.1 Classifications*
At present, there are several types of classification staging of endometriosis.
The two scoring systems most commonly used are stated below.
* Scores can be assessed in the Appendix section of this booklet.
3.1.1 The revised American Society for Reproductive Medicine

score
This scheme is based on the total 3-dimensional volume of endometriosis.
Aspects that are noted include size, depth of invasion, bilaterality, ovarian
involvement, extent of cul-de-sac involvement, as well as density of associated
adhesions.
Scoring system
Point scores are assigned and tallied. Scores ranging from 1 – 15 indicate
minimal or mild disease, 16 – 40 moderate, and >40 severe.
3.1.2 The ENZIAN Staging System

Published in 2005, the ENZIAN score was designed to take into account deep
infiltrating endometriosis (DIE) and act as a supplement to the rAFS (revised
American Fertility and Sterility) score with regards to the description of DIE,
retroperitoneal structures and involvement of other organs (intestinal, uterine,
intrinsic ureteral bladder, other).1
Scoring system2
This scoring system encompasses 3 axes in compartments a, b, and c, and also
classifies the severity of endometriosis (except for ‘other’). The prefix ‘E’ is used
to indicate the presence of an endometriotic tumour. The number that follows
it describes the size of the lesion and subsequent lowercase letter indicates the
location or affected compartment. Two letters would indicate bilateral disease.
References:
1. Tuttlies F, et al. Zentralbl Gynakol. 2005;127(5):275–281.
2. Tuttlies F, et al. J Gynäkol Endokrinol. 2008;18(2):7–13.
8
4.0 Treatment options for pain
Endometriosis is a chronic and usually progressive inflammatory condition of

the pelvis, predominantly presenting as pain. The degree of endometriosis does
not correlate with the severity of symptoms. By necessity, medical therapy is
non-specific and is aimed at alleviating symptoms. Due to its chronic condition,
medical treatments must be effective and safe to use until menopause or until
pregnancy is desired.
4.1. Laparoscopy before commencement of treatment

It is not necessary for laparoscopy before medical management of pelvic pain
begins. In women with severe dysmenorrhoea or chronic pelvic pain that
affects their quality of life, pain management is vital, whether endometriosis
related or not.
Laparoscopy should only be done if the surgeon is prepared to remove the

lesions when endometriosis is discovered. There is good evidence that surgical
intervention provides long-term relief for patients with endometriosis.1
Reference:
1. Duffy JM, et al. Cochrane Database Syst Rev. 2014;4:CD011031
9
4.2 Medical treatment
Figure 4.1: Management of pain associated with suspected

endometriosis
Suspected endometriosis
Trial of medical therapy for 3 months

Responds to
• Combined OCs
therapy
• Progestins
• GnRH agonist with/without addback
• Progestin IUS
• Aromatase inhibitors
No response to
therapy Continue
medical
therapy
Laparoscopy for diagnosis
and treatment
1. Reconsider diagnosis:
additional testing (with or
without non-gynaecological
testing).
2. Chronic pain management
and multidisciplinary support.
10
4.2.1 Combined estrogen and progestin therapy

Oral contraceptives (OCs) that combine estrogen and progestin are considered
as first-line treatment for pelvic pain associated with endometriosis.
Harada et al found that although estrogen-progestin OCs were able to

significantly relieve dysmenorrhoea, there was no difference in non-menstrual
pelvic pain relief when compared to placebo.1 Cyclic treatment with combination
OCs for 3 months has also been shown to only reduce or completely relieve
pain in less than 50% (42%) of patients.2
Data suggests that the continuous administration of OCs, without a 7-day

break, may be more beneficial in terms of pain relief.3,4 This takes into account
the retrograde menstruation theory. By preventing the withdrawal bleeding,
the efficacy of OCs in providing pain relief associated with endometriosis may
be improved.
Despite their potential, combined OCs may not be a universal option in managing
patients with endometriosis-associated pain due to the status of estrogen
and progestin receptors in the ectopic endometrial implants. These implants
have normal estrogen receptors, however the progesterone receptor isoforms
PRA and PRB are reduced or absent. The endometriotic lesions thus may not
recognise progestins and the enzyme 17-β-hydroxysteroid dehydrogenase,
which converts estradiol to estrone, may not be activated by progestin.5,6 The
pharmacologic dose of progestin in OCs are then not recognised and there may
not be any estrogen-antagonistic effect from the medication.
11
4.2.2 Oral progestin therapy

Estrogen stimulates endometriotic growth. OCs contain both estrogen and
progestin. Various progestins in appropriate doses can effectively treat
endometriosis related pain.
4.2.2.1 Dienogest
Dienogest is a progestin with selective 19-nortestosterone and progesterone
activity.7 Pelvic pain and dysmenorrhoea was significantly relieved when
2 mg of dienogest was administered once daily. This dose is as effective
as GnRH agonist therapy in relieving endometriotic pain.8,9 Data has shown
that dienogest, 2 mg daily, was as effective as leuprolide acetate, 3.75 mg
delivered intramuscularly every 4 weeks over a period of 24 weeks, in relieving
dysmenorrhoea, dyspareunia, and pelvic pain.10
Quality of life has been reported to be improved in women receiving dienogest

compared with those receiving leuprolide acetate, although no addback was
used in the latter. There were no side effects related to low levels of estrogen
reported.10
Overall, studies have shown that deinogest is non-inferior to GnRH agonists

and may be effective as a long-term treatment option for endometriosis.11
Common side effects that may be experienced include irregular bleeding,

amenorrhoea, headaches, and constipation.12
4.2.2.2 Norethindrone acetate

Norethindrone acetate, 5 to 20 mg daily, has been effective in most patients
for relieving dysmenorrhoea and chronic pelvic pain.13 This treatment results in
breakthrough bleeding in about half of the patients but seems to have a positive
effect on calcium metabolism, resulting in relatively good maintenance of bone
mineral density (BMD). There may be negative effects on serum levels of high-
density lipoprotein cholesterol. Continuous use of medication is approved by
the US FDA for the treatment of endometriosis.
Some side effects commonly associated with this treatment includes bloating,
weight gain and depression.
12
4.2.3 Depot progestin therapy

Depot medroxyprogesterone acetate (DMPA) is widely used as a method of
contraception. It has also be studied as a form of treatment against pain due
to endometriosis. Two randomised controlled trials (RCTs) have found that
subcutaneous DMPA (DMPA-SC) over a period of 6 months and 12 months, was
equivalent to leuprolide acetate in relieving pain. There was less loss of BMD in
the DMPA group as compared to leuprolide acetate without addback.14,15
Up to 75% of patients find DMPA-SC effective in relieving pelvic pain and is an

economical alternative to the treatment of symptomatic endometriosis. It is
not recommended for women wanting a pregnancy in the near future as there
is a prolonged delay in the resumption of ovulation. Breakthrough bleeding
may also be prolonged, heavy and difficult to correct as the progestin effect
takes a long time to reverse. Long-term use of DMPA may have adverse effects
on BMD.11
4.2.4 Interuterine progestin-releasing system

Levonorgestrel (LNG) causes atrophic endometrium and amenorrhoea in up to
60% patients without inhibiting ovulation.16 Studies have indicated that LNG-
IUS may be useful in reducing pain.17,18
Disadvantages include an expulsion rate of approximately 5% with a risk of

pelvic infection of around 1.5%.19 Treatment with LNG-IUS may be effective as
therapy in adenomyosis.20,21 Irregular menstrual bleeding and amenorrhea are
common side effects though bone density is preserved.22
4.2.5 Danazol
More than 20 years ago, danazol was considered the main medical treatment
for endometriosis. It works by suppressing gonadotropin secretion and
inducing amenorrhoea.23 It is currently rarely used due to side effects such as
acne, weight gain, hirsutism, breast atrophy, and rarely, virilisation24. There
is evidence that danazol has an adverse reaction on blood lipid levels25 and
increases the risk of ovarian cancer in endometriosis patients.26 In view of this,
danazol is not advised for long term use and is preferably prescribed in low-
dose regimens or via vaginal administration.27
13
4.2.6 GnRH agonists

GnRH agonists should be considered as first line treatment for endometriosis
and particularly in women who are unresponsive to combined OCs or progestins
or have a recurrence of symptoms after initial improvement. If used for more
than 6 months or if severe vasomotor symptoms are present, addback hormone
therapy (HT) should be used. HT regimen options are as shown in Box 4.1.
GnRH agonist treatment coupled with induced hyperestrogenism is effective in

managing endometriosis.
GnRH therapy helps in the inactivation of pelvic lesions and resolving the
pain. Unfortunately, symptoms of estrogen deficiency such as breakthrough
bleeding during the first month of therapy, vaginal dryness, irritability, fatigue,
headaches, depression, skin problems and BMD depletion may occur.28
Box 4.1: List of HT addback therapy available in Malaysia29-31
Progynova 1 mg/ 2 mg daily

Conjugated equine estrogen 0.625 mg daily
Norethisterone 5 mg daily
MPA 100 mg daily
Tibolone 2.5 mg daily
4.2.7 Aromatase inhibitors (AI)

This form of treatment for endometriosis is still experimental. The basis for
this treatment is that endometriotic lesions express aromatase and are able to
make their own estrogen even in the absence of gonadotropin stimulation.32
Pilot studies found that 6 months of daily treatment combined with high-dose
norethindrone acetate33 or OCs34 significantly reduced pelvic pain in women
with endometriosis, who did not respond to first-line treatment.
14
In pre-menopausal women, a progestin or combined OC should be added to

aromatase inhibitors to prevent ovarian stimulation and cyst formation due to
the increased gonadotropin secretion which occurs once the estrogen negative
feedback is removed.35 The BMD was found to be stable over 6 months in one
study.36 At present, there still is insufficient evidence and more research needs
to be done for the efficacy and safety of aromatase inhibitors in long-term
treatment for endometriotic pain. The ESHRE 2014 Guidelines recommends the
use of AIs with OCs, progestogens, or GnRH analogues as they reduce pain in
rectovaginal endometriosis, refractory to medical or surgical treatment.37
AI treatment is associated with long- and short-term effects. Some of the

symptoms include hot flushes, vaginal dryness, arthralgia and decrease in
BMD.
4.2.8 Analgesia
Analgesic agents are a useful adjunct in the management of pain related
to endometriosis. These agents include paracetamol, nonsteroidal anti-
inflammatory drugs (NSAIDs), anti-depressants, and in some cases, opioids.
Box 4.2: Practice points for treatent38
• Careful assessment of the pattern of chronic pelvic pain and a trial

of medical treatment should be started empirically if endometriosis
is suspected. If pain persists, proceed with laparoscopy for definitive
diagnosis.
• Treatment should be tailored to the patient, taking age, disease
severity and extent, fertility requirements, contraception, and
patient’s wishes into account.
• In adolescents with symptoms of endometriosis, empirical treatment
with analgesics and/or medical treatment is recommended before
resorting to laparoscopy.
• GnRH agonists may adversely affect the final bone density formation
in adolescents, particularly those under 17 years of age.
15
Key message:
1. Medical management is an important option in the treatment
of endometriosis. If surgical intervention is necessary,
medical intervention can be used before or after the surgery.
2. If a GnRH agonist is used for more than 6 months or if there
are severe vasomotor symptoms, an addback HT must be
considered.
3. Analgesic agents are a useful adjunct in the management of
pain related to endometriosis.
References:
1. Harada T, et al. Fertil Steril 2008;90:1583–1588.
2. Jenkins TR, et al. J Minim Invasive Gynecol. 2008;15:82–86.
3. Coffee AL, et al. Contraception. 2007;75:444–449.
4. Vercellini P, et al. Fertil Steril. 2003;80:560–563.
5. Bulun SF, et al. Mol Cell Endocrinol. 2006;248:94–103.
6. Bulun SF, et al. NEJM. 2009;360:268–279.
7. Sasagawa S, et al. Steroids. 2008;73:222–231.
8. Strowitzki T, et al. Hum Reprod. 2010;25:633–641.
9. Harada T, et al. Fertil Steril. 2009;675–681.
10. Strowitzki T, et al. Efficacy of dienogest for the treatment if endometriosis: a 24- week, randomised, open-label trial
versus leuprolide acetate. Abstract presented at: 25th Annual Meeting of the European Society of Human Reproduction
and Embryology; June 28 – July 1, 2009; Amsterdam.
12. Schindler AE. Int J Womens Health. 2011;3:175–184.
13. Muneyyrici-Delate O, et al. Int J Fertil Womens Med. 1998;43:24–27.
14. Schlaff WD, et al. Fertil Steril. 2006;85:314–325.
15. Crosignani PG, et al. Hum Reprod. 2006;21:248–256.
16. Behamondes L, et al. Contraception. 2007;75(6 Suppl):S134–S139.
17. Anpalagan A and Condous G. J Minim Invasive Gynecol. 2008;15(6):663–666.
18. Sheng J, et al. Contraception. 2009;79(3):189–193.
19. Jain S and Dalton ME. Fertil Steril. 1999;72:852–856.
20. Petta CA, et al. Hum Reprod. 2005;20(7):1993–1998.
21. Bayoglu Tekin Y, et al. Fertil Steril. 2011;95(2):492–496.
22. Wong AY, et al. Aust NZ J Obstet Gynaecol. 2010;50:273–279.
23. Dmowski WP, et al. Fertil Steril. 1971;22:9–18.
24. Selak V, et al. Cochrane Database Syst Rev. 2007;4:CD000068.
25. Packard CJ, et al. Acta Obstet Gynecol Scand Suppl. 1994;159:35–40.
26. Cottreau CM, et al. Clin Cancer Res. 2003;9:5142–5144.
27. Razzi S, et al. Fertil Steril. 2007;88:789–794.
28. Magon N. Indian J Endocrinol Metab. 2011;15(4):261–267.
29. Zupi E, et al. Fertil Steril. 2004;82(5):1303–1308.
30. DiVasta AD, et al. Obstet Gynecol. 2015;126(3):617–627.
31. Pickersgill A, et al. BJOG. 1998;105:475–485.
32. Bulun SE, et al. J Mol Endocrinol. 2000;25(1):35–42.
33. Ailawadi RK, et al. Fertil Steril. 2004;81:290–296.
34. Amsterdam LL, et al. Fertil Steril. 2005;84:300–304.
35. Higgins MJ, et al. Curr Oncol Rep. 2009;11:45–50.
36. Chawla S. Med J Armed Forces India. 2010;66(3):213–215.
37. Dunselman GAJ, et al. Hum Reprod. 2014;29(3):400–412. 19
38. Raffi F. JPOG. 2012;38(3):93–104.
16
4.3 Surgical management of endometriosis

Endometriosis should be viewed as a chronic disease that requires a life-long
management plan with the goal of maximising the use of medical treatment
and avoiding repeat surgical procedures.1 However, it is important to note that
surgery is more effective in reducing pain in patients with more advanced
endometriosis.2 Surgical management of endometriosis requires careful
consideration of the indications of surgery, preoperative evaluation, surgical
techniques, surgeon’s experience, and ancillary techniques and procedures.3
The decision to move to surgery in women in pain and suspected endometriosis

should be based on clinical evaluation, imaging, and effectiveness of medical
treatment. The role of laparoscopy as first line for diagnosis is not recommended.
4.3.1 Indications
Surgical intervention for endometriotic pain is indicated when the patient2:
1. Does not respond to, declines, or has contraindication to medical therapy
2. Has an acute adnexal event (adnexal torsion or ovarian cyst rupture)
3. Has severe invasive disease involving the bowel, bladder, ureters, or pelvic
nerves
4. Has or is suspected to have an ovarian endometrioma >3 cm, especially in
patients for whom the uncertainty of the diagnosis affects the management
(as with chronic pelvic pain)
5. Patients with infertility and associated factors (i.e. pain or a pelvic mass)
caused by endometriosis
Key message:
An asymptomatic patient with an incidental finding of
endometriosis at the time of surgery may not always require any
medical or surgical intervention.
17
4.3.2 Preoperative evaluation

A complete preoperative evaluation will assist in planning the surgical approach,
intraoperative timing and the need for additional procedures and consultations.
There is limited value for the serum CA-125 test in preoperative detection of
endometriosis.4 Thus, the test is not recommended as part of preoperative
routine. Rather, it may be done to evaluate the presence of an undiagnosed
adnexal mass.
Pelvic ultrasonography, particularly transvaginal is recommended when an

adnexal mass is suspected from physical examination. Transrectal sonography,
colonoscopy, barium enema radiography, and MRI may be useful in detecting
the presence of deeply invasive endometriosis of the bowel and rectovaginal
septum in patients with dyschezia and in those with deep dyspareunia with
nodularity upon examination. Cystoscopy should also be performed if there are
cyclic bladder symptoms (e.g. haematuria).
Any risks associated with the surgery should be thoroughly discussed with the
patient. Informed consent should be obtained and documented.
4.3.3 Surgical approach

Surgery can be classified as either “conservative” or “definitive”. The goal of
conservative surgical management of endometriosis is to relieve pain while
restoring normal anatomy. This approach is usually applied to women of
reproductive age and those who wish to conceive in the future or to avoid induction
of menopause at an early age. This may involve ablation, lysis, or excision of
lesions, interruption of nerve pathways, removal of ovarian endometriomas and
excision of lesions invading adjacent organs (bowel, bladder, appendix or ureter).
Conversely, in definitive surgery to induce menopause will include removal

of the uterus, fallopian tubes and both ovaries and excision of all visible
endometriotic nodules and lesions. This form of surgery should only be
considered in women who have had significant pain and symptoms despite
conservative treatment, has severe disease and does not wish to have future
pregnancies or are undergoing a hysterectomy due to other pelvic conditions
(e.g. fibroids or menorrhagia).
18
Laparoscopy is the preferred route for surgical management of endometriosis,

regardless of the severity of the disease. Patient recovery and return to
normal is faster than when compared to laparotomy.5 Patients with invasive
endometriosis including bowel and bladder involvement should be referred to a
multidisciplinary team with more experience or advanced training in managing
this form of endometriosis.6
Adhesion-prevention adjuncts
Adhesions can still form with laparoscopic procedures and the adhesion-related
complications of open and laparoscopic gynaecological surgery are similar.7
Use of antibiotics, NSAIDs, corticosteroids, and fibrinolytics have proven to
be ineffective in preventing adhesions. The use of physical separators (e.g.
gel barriers) have shown reduction in adhesion formation.8 However, more
research is required for the use of other preventive agents as there has been
no evidence on improvement of fertility.
4.3.4 Deeply Infiltrating Endometriosis (DIE)

DIE refers to lesions that penetrate 5mm or more (rectovaginal nodules, bowel
invasion and constriction, bladder invasion, ureteric invasion or compression,
nerve involvement). The lesions are more often than not, multifocal and are
much deeper than perceived. Lesions deeper than 10 mm are usually associated
with pain.9 From the limited evidence available, it has been shown that excision
of these lesions are able to provide pain relief.10,11
Rectovaginal infiltration
Surgery for rectovaginal infiltration requires a multidisciplinary approach with
gynaecologists experienced in minimally invasive surgery, along with a general
surgeon or urologist. For pain relief, bowel surgery may be required12,13 and
should be done by an experienced surgeon or gynaecological oncologist.
If DIE is identified during diagnostic laparoscopy, immediate excision is

not advised. An informed consent should be obtained along with a proper
preoperative evaluation due to the complexity of the disease.
Key message:
Surgical treatment of deeply infiltrating endometriosis requires a
multidisciplinary approach.
19
4.3.5 Ovarian Endometriosis

Ovarian endometriomas are indicative of severe disease and can be a challenge
to manage surgically.14 One of the most important considerations is the
patient’s desire for fertility when determining the level of intervention needed
to preserve the ovaries and their function. In this case, the surgical options
available include excision of the cyst wall or drainage, and coagulation of the
cyst bed.
In terms of pain, evidence suggests that laparoscopic excision of the

endometriomas is more beneficial than simple laparoscopic ablation. Excision
results in lower rates of recurrence, dysmenorrhoea, dyspareunia, non-
menstrual pelvic pain, and requirement for additional surgery. The cumulative
pregnancy rate in this group of patients is also higher than those that underwent
cystectomy.15
Despite the benefits of laparoscopic excision of ovarian endometriomas, it

usually involves the unintentional removal of normal ovarian tissue.16 During
the excision, it is important preserve as much normal ovarian tissue as possible.
Decisions to treat endometriomas surgically needs to be based on clinical
presentation, particularly after the risks of unintentional removal of normal
ovarian tissue has been considered. Excisions may be more suitable for larger
endometriomas (>3 cm in diameter) in the presence of pelvic pain. For smaller
cysts, a simple drainage and ablation or expectant management may suffice.
Ovarian endometriomas tend to recur in 30% of patients after laparoscopic

excision.17 It has been observed that lower recurrence rate and better
management of symptoms can be achieved through postoperative hormonal
suppression.18,19 In patients that do not wish to conceive, combined OCs (cyclic
or continuous), should be considered after surgery. As risk of malignancy is
low and there is no evidence on fertility improvement, the decision for repeat
surgery should be based on the symptoms and size of the cyst.
20
4.3.6 Additional surgical interventions

During laparoscopy, the appendix and other peritoneal organs should be
visualised. In addition to ablation or excisions of endometriotic lesions, there
are other surgical interventions available to help relieve pelvic pain. In large
randomised trials, uterosacral nerve ablation has not proven to be effective in
providing chronic pain relif.20
Key message:
1. In the case of ovarian endometriomas, it is crucial that the
patient’s desire for fertility be considered when determining
the degree of intervention needed to preserve the ovaries and
their function.
2. Ovarian endometriomas are usually indicative of more
extensive endometriosis.
3. Ovarian endometriomas larger than 3 cm in diameter in
women with pelvic pain should be excised as soon as possible.
4. In patients that do not wish to conceive, therapy with
combined OCs (cyclic or continuous) should be considered
after surgical management of ovarian endometriomas.
References:
1. The Practice Committee of the Americal Society for Reproductive Medicine. Fertil Steril. 2008;90:260–269.
2. Raffi F. JPOG. 2012;38(3):96–104.
4. Bedaiwy MA and Falcone T. Clin Chim Acta. 2004;340(1 – 2):41–56.
5. Crosignani PG, et al. Fertil Steril. 1996;66:706–711.
6. Singh SS, et al. J Minim Invasive Gynecol. 2009;16(1):1–7.
7. Lower AM, et al. Br J Obstet Gynaecol. 2000;107:855–862.
8. DeWilde RL and Trew RG. Gynecol Surg. 2007;4:243–253.
9. Cornillie FJ, et al. Fertil Steril. 1990;53:978–983.
10. Chopin C, et al. J Minim Invasive Gynecol. 2005;12:106–112.
12. Darai E, et al. Curr opin Obstet Gynecol. 2007;19:308–313.
13. Mereu T, et al. J Minim Invasive Gynecol. 2007;14:463–469.
14. Chapron C, et al. Fertil Steril. 2009;92:453–457.
15. Hart RJ, et al. Cochrane Database Syst Rev. 2008;16(2):CD004992.
16. Matsuzaki S, et al. Hum Reprod. 2009;24:1402–1406.
17. Koga K, et al. Hum Reprod. 2006;21:2171–2174.
18. Seracchioli R, et al. Hum Reprod. 2009;24:2729–2735.
19. Seracchioli R, et al. Fertil Steril. 2010;94(2):464–471.
20. Daniels J, et al. JAMA. 2009;302:955–961.
21
5.0 Fertility Issues
Endometriosis is common in women with infertility. However, the clinical

management of the infertility in these patients is difficult because many clinical
decision end-points have not been evaluated in randomized controlled trials.
Furthermore, existing data is often conflicting. Therefore, its management is
often controversial and varied.
It has been suggested that 25% to 50% of infertile women have endometriosis,
while 30% to 50% of women with endometriosis are infertile.1 However, the
true prevalence of endometriosis is difficult to quantify. Some studies suggest
that the prevalence of endometriosis among the fertile population may be 1%
to 7%.1
The exact reason why endometriosis causes infertility is still unknown. Possible
reasons include distorted pelvic anatomy, altered peritoneal function, altered
hormonal and cell-mediated function, abnormalities in endocrine and ovulation,
and impaired implantation. Abnormalities in oocyte and embryo quality as
well as abnormal utero-tubal transport have also been suggested as possible
mechanisms.
5.1 Diagnosis
The combination of laparoscopy and the histological confirmation of endometrial
glands and/or stroma is considered the gold standard for the diagnosis of the
disease.
It is therefore required for a definitive diagnosis of endometriosis to be made.

However, in patients with infertility but who are otherwise asymptomatic,
laparoscopy merely to confirm or exclude the diagnosis is not warranted. This
is largely because the therapeutic benefit of laparoscopy to increase fecundity
in women with minimal or mild disease is minimal.2,3
References:
1. Missmer MA, et al. AM J Epidemiology. 2004;160:784–796.
2. Marcoux S, et al. NEJM. 1997;337:217–222.
3. Parazzini F. Hum Reprod. 1998;14(5):1332–1334.
22
5.2 Medical therapy
A. Before fertility treatment (without surgery)

Medical therapy does not improve fertility.
B. Before surgery
In infertile women with endometriosis, adjunctive hormonal therapy before
surgery should not be prescribed as it has not been shown to improve pregnancy
rates.
However, in symptomatic women, medical treatment is reasonable while

waiting for surgery or assisted reproductive treatment.
C. Medical treatment after surgical treatment

There is no evidence that post-surgical adjuvant therapy significantly improves
fertility but may instead unnecessarily delay further fertility treatment.1
D. Medical treatment before assisted reproductive treatments

Down-regulation with GnRH agonists for a period of 3-6 months prior to
treatment with assisted reproductive treatment may improve clinical pregnancy
rates in infertile women with endometriosis2,3
References:
1. Furness S, et al. Cochrane Database Syst Rev. 2004;CD003678.
2. Sallam HN, et al. Cochrane Database Syst Rev. 2006;(1):CD004635.
3. Rickes D, et al. Fertil Steril. 2002;78:757–762.
23
5.3 Surgical treatment
5.3.1: Indications for surgery
A. For diagnosis only

Laparoscopy in asymptomatic women merely to confirm or exclude the
diagnosis is not warranted.
The therapeutic benefit of laparoscopy to increase fecundity in women with

minimal or mild disease is negligible. Therefore, it may be of value only in
symptomatic women.
B. In mild endometriosis
In stage 1/11 endometriosis, laparoscopic ablation of endometrial implants
may improve spontaneous pregnancy rates and has also been associated with
a small but significant improvement in live birth rates.
C. In severe endometriosis
In infertile women with AFS/ ASRM stage III/IV endometriosis, operative
laparoscopy instead of expectant management increases spontaneous
pregnancy rates.1,2
D. In women already planned for IVF/ICSI

In women planned for IVF/ICSI, there is insufficient data to suggest that the
removal of the endometrioma would improve IVF success rates.3-5
However removal may be considered for the following reasons:

a) To confirm the diagnosis histologically
b) To improve access to follicles during the oocyte retrieval
c) Possibly to improve ovarian response
E. Treatment of endometriomas and deeply infiltrating endometriosis

and infertility
There is no evidence that surgical excision of deep nodular lesions prior to ART
will improve reproductive outcome.6,7
24
5.3.2 Laparotomy versus laparoscopy

The preferred surgical approach for treatment of infertility related to
endometriosis is laparoscopy. This is because laparoscopy is usually associated
with less pain, shorter hospital stay, quicker recovery and a better cosmetic
outcome.8
5.3.3 Surgical principles, procedures and techniques

A. The purpose of surgery is:
1. To determine the severity of the disease by staging and looking at other
areas, such as the appendix, bowel, and diaphragm.
2. The removal of the endometriotic lesions as much as possible.
3. To restore the normal anatomy with adhesiolysis.
4. To optimise ovarian and tubal preservation and integrity by using the
principles of microsurgery (magnification, diligent haemostasis, reduced
fulguration, avoidance of tissue drying, and limited use of sutures).
5. To evaluate (if there is suspicion) the adnexa, through peritoneal cytology
and frozen section in case of doubt.
6. Performing a blue dye test to evaluate tubal patency. The further
management options of a blocked tube and/or hydrosalphinx should have
been discussed prior to the surgery.
B. Surgical techniques
The surgical procedure of choice in women with an ovarian endometrioma
should be excision of the endometrioma capsule, instead of drainage and
coagulation, to increase spontaneous pregnancy rates.
In addition, there was a decreased rate of recurrence and no difference in

response to gonadotrophin stimulation.4,9
A cystectomy is also preferred to a CO2 laser vaporization as it is associated

with a lower rate of recurrence.10
C. Issues to discuss with patients prior to surgery:

A detailed discussion is warranted prior to surgery, especially with regards to:
a) Reduced ovarian reserve: Ovarian reserve may already be reduced
in the presence of an endometrioma. Ovarian surgery if extensive may
also compromise ovarian function and reserve, hence causing diminished
ovarian response to stimulation.
25
b) Management of a hydrosalphinx: the need to assess tubal patency during

surgery and if a hydrosalphinx is discovered, the possible need to either
remove or clip the relevant tube / tubes. The possibility of tubal surgery
should also be discussed.
c) Recurrence rates: the endometriotic cyst is likely to recur and therefore the
window of opportunity for fertility must be optimized.
5.3.4 Recurrent surgery

Additional surgery after the first fertility operation rarely increases fecundability,
and in these patients, it may be better to refer them for ART.
Pregnancy rates have been shown to be halved after repeat surgery when
compared to first line surgery.11
Therefore, it is imperative that the initial surgery is well planned, with future
reproductive treatment options discussed and referred to the appropriate
expertise.
The decision to undertake repeat surgery should depend on:

1. Presence of symptoms
2. Presence of complex cysts requiring histological diagnosis
3. Age
4. Ovarian reserve
5. Presence of male factor infertility
6. Surgical skill
7. Costs
8. Time to conception considerations
References:
1. Nezhat C, et al. Fertil Steril. 1989;51(2):237 – 240.
2. Vercellini P, et al. Am J Obstet Gynecol. 2006;195(5):1303–1310.
3. Donnez J, et al. Fertil Steril. 2001;76(4):662–665.
4. Hart RJ, et al. Cochrane Database Syst Rev. 2008;2:CD004992.
5. Benschop L, et al. Cochrane Database Syst Rev. 2010;10:CD008571.
6. Bianchi PH, et al. J Minim Invasive Gynecol. 2009;16(2):174–180.
7. Papaleo E, et al. Acta Obstet Gynecol Scand. 2011;90(8):878–884.
8. Royal College of Obstetricians and Gynaecologists (RCOG). RCOG Guideline No. 24. (2006).
9. Brown J and Farquhar C. Cochrane Database Syst Rev. 2014;3:CD009590.
10. Carmona F, et al. Fertil Steril. 2011;96(1):251–254.
11. Vercellini P, et al. Fertil Steril. 2009;92:1253–1255.
26
5.4 Options after surgery

In women with stage I/II endometriosis the following options may be
offered:
1. Expectant management
2. Superovulation with IUI (SO/IUI)
3. IVF
A key determining factor when deciding between the three options is female
age. It is well documented that there is significantly decreased fecundity after
age 35 years.
Fecundity may be decreased further due to endometriosis. Therefore, in older

women more aggressive options (SO/IUI or IVF) should be offered.
In women with stage III/IV endometriosis:
The initial surgical intervention may restore fertility in these patients. If this
fails, IVF is an effective alternative.
In women with advancing reproductive age, consider IVF sooner.
In women with stage III/IV endometriosis and have had previous fertility
surgery (once or more), IVF is likely a better therapeutic option than another
surgical intervention.
27
5.5 Assisted reproduction
5.5.1 Super-ovulation and intrauterine insemination

(SO/IUI)
In infertile women with AFS/ASRM stage I/II endometriosis, IUI with controlled
stimulation instead of expectant management increases live birth rates.1
Controlled ovarian stimulation is better than IUI alone as it increases pregnancy

rates.2
IUI with controlled stimulation may commence within six months after surgical
treatment.3
However, women with endometriosis have a lower clinical pregnancy rate

following controlled ovarian hyperstimulation-IUI (COH-IUI) compared to
women having COH-IUI for other indications
5.5.2 In vitro fertilisation (IVF)

IVF may maximise cycle fecundity for those with endometriosis especially
where there is distortion of pelvic anatomy due to moderate or severe disease.
In women who fail to conceive after surgery or because of advancing

reproductive age, IVF should be considered.
However, it is likely that endometriosis affects IVF results.
Women with endometriosis have lower clinical pregnancy rates following in

vitro fertilization compared to women with other aetiologies. This effect is even
greater with the increasing severity of the disease.
The clinical pregnancy rate per woman was found to be significantly higher in
women receiving GnRH agonist down regulation for 3 to 6 months prior to IVF
– than compared to those that did not.4
References:
1. Tummon IS, et al. Fertil Steril. 1997;68(1):8–12.
2. Nulsen JC, et al. Obstet Gynecol. 1993;82(5):780–786.
3. Werbrouck E, et al. Fertil Steril. 2006;86(3):566–571.
4. Sallam HN, et al. Cochrane Database Syst Rev. 2006 Jan 25;1:CD04635.
28
6.0 Post-menopausal management of endometriosis
Generally, post-menopausal endometriosis is rare as estrogenic-hormone

production should have ceased. The estimated incidence of post-menopausal
endometriosis is between 2–4%, a bulk of which is generally recurrence due
to hormone therapy.1
6.2 Pathogenesis of post-menopausal endometriosis

The ovaries are the main source of estrogen. In post-menopausal women,
estrogen is derived from either exogenous administration or from endogenous
extra ovarian production. Exogenous administration is usually in the form of
hormone therapy (HT)2 while endogenous extra ovarian production arises from
the skin and adipose tissue. Obese post-menopausal women tend to produce
more endogenous estrogen than non-obese women.3
6.3 Treatment options of post-menopausal endometriosis

In the treatment of post-menopausal endometriosis, surgery is the first-line
management as any post-menopausal mass carries the risk of developing
into a malignancy.2 Young women who have had a hysterectomy with removal
of the ovaries requiring hormone therapy should receive combined hormone
therapy (estrogen and progestin) or tibolone.4-6 The addition of a progestin
may be unnecessary after a hysterectomy but protects against the unopposed
action of the estrogen on any lesion.
Key messages:
1. HT may cause a recurrence of endometriosis in post-
menopausal women. It is crucial to consider the risks and
benefits of administering HT to patients with previous
endometriosis.
2. Surgery should be considered as first-line treatment for
post-menopausal endometriosis with follow-up to monitor for
recurrence.
3. If HT is required, combined hormone therapy or tibolone can
be used.
References:
1. Sasson IE and Taylor HS. Fertil Steril. 2009;92(3):1170e1–1170e4.
2. Polyzos NP, et al. Reprod Biol Endocrinol. 2011;9:90.
3. Jeon D-S, et al. J Menopausal Med. 2013;19:151–153.
4. Matorras R, et al. Fertil Steril 2002;77:303-308.
5. Brown J and Farquhar C. Cochrane Database Syst Rev. 2014;3:CD009590.
6. Roberts AL and Lashen H. Int J Gynaecol Obstet. 2010;111(2):183.
29
7.0 Endometriosis and the risk of cancer
Endometriosis is generally a benign disease that shares traits similar to

malignancy: invasive and unrestricted growth, tendency to metastasize and
recur. There are epidemiological and laboratory evidence that link endometriosis
to epithelial ovarian carcinoma.
7.1 Epidemiology
Scott1 added a fourth criterion in 1953 for the malignancy originating from
endometriosis (Box 7.1) to the three other criteria added by Sampson.2 Since
then, there has been numerous studies that have supported the relationship
between endometriosis and epithelial ovarian carcinoma, especially in clear cell
and endometroid subtypes.3
Box 7.1: Criteria for malignancy originating from endometrosis
1. The presence of both endometriosis and malignancy within the

same ovary must be demonstrated.
2. The carcinoma must arise from the endometriosis and not invade it
from another source
3. The specimen must contain histological characteristics of
endometriosis, including stroma and glands.
4. Malignant transformation or transition occurring in benign ovarian
endometriosis.
A retrospective cohort study of >20,000 women with endometriosis found an

overall increased cancer risk and a greater increase in risk of ovarian cancer.4
A recent study found that the hazard ratio associated with endometriosis was
12.4 for ovarian cancer and 5.5 for borderline ovarian tumours. The study
concluded that there is an estimate of 3- to 8-fold increase risk of ovarian
tumours associated with endometriosis.5
30
7.2 Pathophysiology
While the evidence that shows the link between endometriosis and ovarian
cancer is strong, little is known of the mechanism that causes the malignant
transformation. In a review by Somigliana et al,6 it was suggested that
endometriotic cells may undergo malignant transformation, and the coexistence
of endometriosis and ovarian cancer may be due to shared risk factors and
preceding mechanisms.
It is suggested that endometriosis is the precursor lesion to ovarian cancer.

This theory is derived from histologic evidence of malignant transformation
of the endometriosis to clear cell or endometrioid carcinoma.7 Molecular
genetic alteration studies have also provided evidence that endometriosis is
the precursor lesion to carcinoma; however, more research is needed to fully
define this progression.8,9
Somigliana also suggested that endometriosis and ovarian cancer are two
separate biological entities that are bound by an indirect link as the two
diseases share similar risk factors. For instance, nulliparity, early menarche,
late menopause3 and other similar risk factors (e.g. genetic predisposition,
immune dysregulation, and environmental factors).6
While there seems to be a link between endometriosis and ovarian cancer, this
does not prove causality.
31
7.3 Management
If there is suspicion of ovarian malignancy in an endometriotic cyst, the
management will follow the standard guidelines for this condition.
Key message:
1. While there is a link between endometriosis and certain
cancers, there is no conclusive evidence that indicates that
endometriosis causes cancer.
2. Some cancers (ovarian cancer and non-Hodgkin’s lymphoma)
are slightly more common in women with endometriosis.6
References:
1. Scott RB. Obstet Gynecol. 1953;2:283–289.
2. Sampson JA. Arch Surg. 1925;10:1–72.
3. Nezhat F, et al. Fertil Steril. 2008;90:1559–1570.
4. Brinton LA, et al. Am J Obstet Gynecol. 1997;176:572–579. 5 Buis CC, et al. Hum Reprod. 2013;28(12):3358–3369.
6. Somigliana E, et al. Gynecol Oncol. 2006;101:331–341.
7. Feeley KM and Wells M. Histopathology. 2001;38:87–95.
8. Prowse AH, et al. Int J Cancer. 2006;119:556–562.
9. Otsuka J, et al. Med Electron Microsc. 2004;37:188–192.
32
Appendix
American Society of Reproductive Medicine Score
Classification of Endometriosis
Name:____________________________________________________Date:________________________
Procedure performed:___________________________________________________________________
ENDOMETRIOSIS <1cm 1-3cm >3cm
Peritoneum Superficial 1 2 4
Deep 2 4 6
Ovary Right Superficial 1 2 4
Deep 4 16 20
Left Superficial 1 2 4
Deep 4 16 20
POSTERIOR CUL-DE-SAC OBLITERATION Partial Complete
4 40
<1/3 1/3-2/3 >2/3

ADHESIONS
Enclosure Enclosure Enclosure
Ovary R Filmy 1 2 4
Dense 4 8 16
L Filmy 1 2 4
Dense 4 8 16
Tube R Filmy 1 2 4
Dense 41 81 16
L Filmy 1 2 4
Dense 41 81 16
1. If the fimbriated end of the Fallopian tube is completely enclosed, change the point assignment to 16.
Staging: stage I (minimal): 1-5; stageII (mild): 6-15; stage III (moderate): 16-40; stage IV (severe): >40.
Revised ASRM Classification. Fertil Steril 1997;67:819.
33
Appendix
Additional Endometiosis:
To be used with normal tubes and ovaries
L R
Associated Pathology:
To be used with abnormal tubes and/or ovaries
L R
34
Appendix
STAGE I (MINIMAL) STAGE II (MILD)
PERITONEUM PERITONEUM
Superficial Endo 1-3cm 2 Deep Endo >3cm 6
Right OVARY Right OVARY
Superficial Endo <1cm 1 Superficial Endo <1cm 1
Filmy Adhesions 1/3 1 Filmy Adhesions <1/3 1
Left OVARY
TOTAL POINTS 4 Superficial Endo <1cm 1
TOTAL POINTS 9
STAGE III (MODERATE) STAGE III (MODERATE)
PERITONEUM
Deep Endo >3cm 2 PERITONEUM
Superficial Endo >3cm 4
CULDESAC
4 Right TUBE
Partial Obliteration
Filmy Adhesions <1/3 1
Left OVARY
1-3cm 16 Right OVARY
Deep Endo
Filmy Adhesions <1/3 1
TOTAL POINTS 26
Left TUBE
Dense Adhesions <1/3 16*
Left OVARY
STAGE IV (SEVERE) Deep Endo 1-3cm 4
Dense Adhesions <1/3 4
TOTAL POINTS 30
STAGE IV (SEVERE)
PERITONEUM
Deep Endo >3cm 6
CULDESAC
Complete Obliteration 40
Right OVARY
Deep Endo 1-3cm 16 PERITONEUM
Dense Adhesions <1/3cm 4 Superficial Endo >3cm 4
Left TUBE Left OVARY
Dense Adhesions >2/3cm 16 Deep Endo <1cm 32**
Left OVARY Deep Adhesions <1/3 8**
Deep Endo 1-3cm 16 Left TUBE
Dense Adhesions >2/3cm 16 Dense Adhesions >3cm 8**
TOTAL POINTS 114 TOTAL POINTS 52
*Point assignment changed to 16 **Point assignment doubled
35
Appendix
Enzian Staging System

Enzian Score
a b c
* cul-de-sac * uterosacral ligament * bowel, rectum
* vagina * cardinal ligament * rectosigmoid
E1a = isolated nodule the pouch of Douglas E1b = isolated E1bb = bilateral infiltration E1c = isolated
nodule <1 cm of the USL nodule in the
from the uterine rectovaginal
sacral ligament (USL) space
E2a = infiltration of the upper E2b = infiltration E2bb = bilateral E2b =

third of the vagina of the USL >1 cm infiltration of
rectum <1 cm
E3a = infiltration of the middle E3b = infiltration of E3bb = bilateral E3c =

part of the vagina the cardinal ligament infiltration of the
(without rectum 1-3 cm
ureterohydronephrosis) without stenosis
E4a = infiltration of uterus E4b = infiltration of the E4bb = bilateral E4c =

and/or lower third of the vagina cardinal ligament to infiltration of
pelvic side wall and/or the rectum
ureterohydronephrosis >3 cm and/or
rectal stenosis
FA = adenomyosis uteri FB = deep infiltration FU = ureteral infiltration FI = intestinal

of the bladder (intrinsic) infiltration (other
side than rectum or
FO = other locations sigmoid)
36
Notes
37
Notes
38
Appendix
39
Appendix
40

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Clinical Guidelines for the

Clinical Guidelines for the Management of Endometriosis

Guidelines development group i

5.0 Fertility Issues 21

Members (in alphabetical order)

Dr Tham Seong Wai

At present, there is no consensus on what is the cause of this disease. Healthcare

Purpose of this proposed guideline

2.1 The basic science of endometriosis

On a cellular level, the failure of immune mechanisms to destroy ectopic

The failure of immune mechanisms to destroy ectopic tissue and prevent

The theory of retrograde menstruation, whereby the menstrual tissue refluxes

Increased estrogen sensitivity along with an increase in progesterone

Endometriotic cell survival and growth and associated inflammation are

There are several types of endometriosis:

Peritoneal endometriosis: Peritoneal implants that consist of glandular

Ovarian endometriomas: Benign, estrogen-dependent cyst also known as

Deep endometriosis (DE): This form of endometriosis is characterised

Adenomyosis: Uterine endometriosis presents as asymmetrical uterine

Disseminated endometriosis: Growth of endometriotic tissue in various

Pain in endometriosis presents as any of the following:

Atypical presentations include cyclic leg pain or sciatica (nerve involvement),

Physical examinations may present with the following3:

3.0 Diagnosis – Laparoscopy versus clinical

Figure 1: Diagnostic pathway1*

*adapted from the SOGC Guidelines

Generally, diagnosis of endometriosis is based on the history, the

3.0 Diagnosis – Laparoscopy versus clinical

Ultrasonography is the first-line investigational tool for suspected endometriosis.

It has been traditionally believed that laparoscopy must be performed to definitely

Diagnostic laparoscopy should be done by an experienced laparoscopic

Diagnostic laparoscopy is not required before treatment of all patients with

3.0 Diagnosis – Laparoscopy versus clinical

When endometriosis is thought to be of the DE variety, ancillary tests such as

3.0 Diagnosis – Laparoscopy versus clinical

3.1.1 The revised American Society for Reproductive Medicine

3.1.2 The ENZIAN Staging System

4.0 Treatment options for pain

Endometriosis is a chronic and usually progressive inflammatory condition of

4.1. Laparoscopy before commencement of treatment

Laparoscopy should only be done if the surgeon is prepared to remove the

4.0 Treatment options for pain

4.2 Medical treatment

Figure 4.1: Management of pain associated with suspected

Trial of medical therapy for 3 months

4.0 Treatment options for pain

4.2.1 Combined estrogen and progestin therapy

Harada et al found that although estrogen-progestin OCs were able to

Data suggests that the continuous administration of OCs, without a 7-day

4.0 Treatment options for pain

4.2.2 Oral progestin therapy

Quality of life has been reported to be improved in women receiving dienogest

Overall, studies have shown that deinogest is non-inferior to GnRH agonists

Common side effects that may be experienced include irregular bleeding,

4.2.2.2 Norethindrone acetate

4.0 Treatment options for pain

4.2.3 Depot progestin therapy

Up to 75% of patients find DMPA-SC effective in relieving pelvic pain and is an

4.2.4 Interuterine progestin-releasing system