2. CONTENTS
I. DIAGNOSIS
II. TREATMENT OF PAIN ASSOCIATED
ENDOMETRIOSIS
III.TREATMENT OF INFERTILITY ASSOCIATED
ENDOMETRIOSIS
IV.OTHER
1. Menopause in women with endometriosis
2. Asymptomatic endometriosis
3. Prevention of endometriosis
4. Endometriosis & cancer
ABOUBAKR ELNASHAR
5. Suspect endometriosis
(NICE, 2017)
with 1 or more of the following symptoms or signs:
1. chronic pelvic pain
2. period-related pain (dysmenorrhoea) affecting daily
activities and quality of life
3. deep pain during or after sexual intercourse
4. period-related or cyclical gastrointestinal symptoms,
in particular, painful bowel movements
5. period-related or cyclical urinary symptoms, in
particular, blood in the urine or pain passing urine
6. infertility in association with 1 or more of the above.
ABOUBAKR ELNASHAR
6. 2. Examination
In all women suspected of endometriosis
Vaginal:
Rectal: adolescents and/or women without
previous sexual intercourse.
(GPP)
Deep endometriosis:
Painful induration and/or nodules of the rectovaginal
wall or
Visible vaginal nodules in the posterior vaginal fornix
(Bazot et al., 2009). (C)
ABOUBAKR ELNASHAR
7. Ovarian endometrioma
Adnexal masses
(Ripps and Martin, 1992; Koninckx et al., 1996; Eskenazi et al., 2001;
Condous et al., 2007; Bazot et al., 2009). {C}
Endometriosis
suspected even if the clinical examination is normal
(Chapron et al., 2002). {C}
ABOUBAKR ELNASHAR
8. 3. Investigations
1. Laparoscopy
with biopsy and histology:
gold standard for diagnosis
Negative diagnostic laparoscopy:
highly accurate for excluding endometriosis
Positive laparoscopy without taking biopsies
less informative
of limited value
(Wykes et al., 2004).
To obtain tissue for histology in women undergoing
surgery for
endometrioma and/or
deep infiltrating disease
{exclude rare instances of malignancy}
{GPP}
ABOUBAKR ELNASHAR
10. Diagnostic laparoscopy (NICE, 2017)
Is considered in women with suspected
endometriosis, even if the ultrasound was normal.
gynaecologist with training and skills in
laparoscopic surgery for endometriosis
perform a systematic inspection of the pelvis.
ABOUBAKR ELNASHAR
11. 2. TVS:
To diagnose or to exclude
ovarian endometrioma
(Moore et al., 2002).{A}
rectal endometriosis
(Hudelist et al., 2011).{A}
ABOUBAKR ELNASHAR
13. Endometrioma. Sagittal TVS
an ovarian mass with multiple fine internal echoes (arrows) and
several hyperechoic mural foci (arrowheads).
ABOUBAKR ELNASHAR
14. Ovarian endometrioma (A, B).
The structure is hypoechoic and exhibits low amplitude
uniformly distributed echotexture in the cavities of the
cysts.ABOUBAKR ELNASHAR
15. 3D ultrasound
To diagnose rectovaginal endometriosis is not well
established
(Pascual et al., 2010).{D}
MRI
To diagnose peritoneal endometriosis is not well
established
(Stratton et al., 2003) {D}
For women with suspected deep endometriosis
involving the bowel, bladder or ureter, consider a
pelvic ultrasound or
MRI before an operative laparoscopy.
(NICE, 2017)
ABOUBAKR ELNASHAR
16. MRI (NICE, 2017)
Do not use pelvic MRI as the primary investigation
to diagnose endometriosis in women with
symptoms or signs suggestive of endometriosis.
Consider pelvic MRI to assess the extent of deep
endometriosis involving the bowel, bladder or
ureter.
Ensure that pelvic MRI scans are interpreted by a
healthcare professional with specialist expertise in
gynaecological imaging.
ABOUBAKR ELNASHAR
17. Biomarkers
Not recommended to diagnose endometriosis
in endometrial tissue, menstrual or uterine fluids
(May et al., 2011)
Immunological biomarkers
CA-125, in plasma, urine or serum
(Mol et al., 1998;May et al., 2010).{A}
ABOUBAKR ELNASHAR
18. Serum CA125 (NICE, 2017)
Do not use serum CA125 to diagnose
endometriosis.
If a coincidentally reported serum CA125 level is
available, be aware that:
a raised serum CA125 (that is, 35 IU/ml or
more) may be consistent with having
endometriosis
endometriosis may be present despite a
normal serum CA125 (less than 35 IU/ml).
ABOUBAKR ELNASHAR
19. Barium enema, TVS, TRS and MRI
To assess ureter, bladder and bowel involvement
if there is a suspicion (based on history or physical
examination) of deep endometriosis
for further management
{GPP}
ABOUBAKR ELNASHAR
20. Staging systems
(NICE, 2017)
Offer endometriosis treatment according to the
woman's symptoms,
preferences and priorities, rather than the stage of
the endometriosis.
When endometriosis is diagnosed, the gynaecologist
should document a detailed description of the
appearance and
site of endometriosis.
ABOUBAKR ELNASHAR
21. II. TREATMENT OF ENDOMETRIOSIS-
ASSOCIATED PAIN
ABOUBAKR ELNASHAR
22. Pathogenesis of endometriosis-associated pain
Central Sensitization
key factor in the in addition to the peripheral
nociceptive effect* of endometriotic lesions
(Hoffman, 2015).
amplifies pain signaling from the periphery
(Brawn et al , 2014).
It is associated with
Myofascial trigger points
(Stratton et al, 2015)
Psychological comorbidities
(Yosef et al, 2016).
*Pain that arises from damage to non-neural tissue.
due to the activation of nociceptors=
sensory receptor of the peripheral nervous system
ABOUBAKR ELNASHAR
24. Central sensitisation
an important mechanism in endometriosis-
associated pain and CPP
Increased responsiveness of nociceptive neurons in
the CNS to their
normal or
sub-threshold afferent input:
patient becomes more sensitive to peripheral
stimuli.
ABOUBAKR ELNASHAR
25. Central sensitization:
may become independent of peripheral stimuli
{via neural mechanisms similar to those underlying
the generation of memory}:
generation of pain without a peripheral noxious
input.
This may be a reason
why pain can persist despite treatment of all
identified peripheral pathology
ABOUBAKR ELNASHAR
26. EMPIRICAL TREATMENT OF PAIN
counsel women with symptoms presumed to be
due to endometriosis thoroughly, and to empirically
treat them with
Adequate analgesia
COC or
Progestagens.
ABOUBAKR ELNASHAR
27. Clinicians are recommended to prescribe hormonal
treatment
hormonal contraceptives (Level B)
progestagens (Level A)
anti-progestagens (Level A) or
GnRH agonists (Level A)] as one of the options, as
it reduces endometriosis-associated pain
(Vercellini et al.,1993; Brown et al., 2010, 2012).
ABOUBAKR ELNASHAR
28. Clinicians take into consideration when choosing
hormonal treatment for endometriosis-associated
pain.
Patient preferences
Side effects
Efficacy,
Costs and
Availability (GPP)
ABOUBAKR ELNASHAR
29. Hormonal contraceptives.
COC:
{reduces endometriosis-associated dyspareunia,
dysmenorrhoea and non-menstrual pain}
(Vercellini et al., 1993).B
continuous use in women suffering from
endometriosis-associated dysmenorrhoea
±consider
vaginal contraceptive ring or
transdermal (oestrogen/progestin) patch
(Vercellini et al., 2010).C
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31. Progestagens and anti-progestagens.
Progestagens
Medroxyprogesterone acetate (oral or depot),
dienogest
Cyproterone acetate,
norethisterone acetate or
danazol or
anti-progestagens
(gestrinone) as one of the options, to reduce
endometriosis-associated pain
(Brown et al., 2012).A
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32. Dose:
Continuously:
Progestagens given in the luteal phase are not
effective
DoseNamePreparation
30mg/dProveraMPA
150mg/1- 3 mo, IM.Depo proveraDMPA
10-20 mg/d.Primoult norNoreethisterone acetate
20 mg/dDuphastonDydrogestrone
2mg/dVisanneDienogest
ABOUBAKR ELNASHAR
33. Take in consideration
side-effect especially irreversible side effects
e.g. thrombosis and androgenic side effects. GPP
Consider prescribing
LNG-IUS as one of the options to reduce
endometriosis-associated pain
(Petta et al., 2005; Gomes et al., 2007;Ferreira et al., 2010).
ABOUBAKR ELNASHAR
34. GnRH agonists
Nafarelin, leuprolide, buserelin, goserelin or
triptorelin, as one of the options for reducing
endometriosis-associated pain
Evidence is limited regarding dosage or duration
(Brown et al., 2010).A
Careful consideration in young women and
adolescents, since these women may not have
reached maximum bone density. GPP
ABOUBAKR ELNASHAR
35. Hormonal add-back therapy to coincide with the start
of GnRHagonist therapy
{prevent bone loss and hypoestrogenic symptoms
during treatment}.
This is not known to reduce the effect of treatment on
pain relief
(Makarainen et al., 1996; Bergqvist et al., 1997; Taskin et al., 1997;
Moghissi et al., 1998). A
ABOUBAKR ELNASHAR
38. Aromatase inhibitors.
In women with pain from
Rectovaginal endometriosis
Refractory to other medical or surgical treatment
in combination with
COC,
progestagens or
GnRH analogues, as they reduce endometriosis-
associated pain
(Nawathe et al., 2008; Ferrero et al., 2011).B
ABOUBAKR ELNASHAR
40. Analgesics
NSAIDs or
other analgesics to reduce endometriosis-associated pain.
Useful in women trying to conceive
ibuprofen (Sapofen)
naproxen (Naprosyn).
Mefenamic acid (Ponstan)
Start 2 d before menstruation, Similar efficacy
Gastric irritation.
ABOUBAKR ELNASHAR
41. Cyclooxygenase-2 (COX-2).
Celebrex
Vioxx
Not more effective (than naproxen or ibuprofen)
lower risk of gastric ulceration
high cost
(Mahutte & Arici, 2003)
ABOUBAKR ELNASHAR
42. Analgesics (NICE, 2017)
discuss the benefits and risks of analgesics, taking
into account
any comorbidities and
woman's preferences.
Consider a short trial (for example, 3 months) of
paracetamol or a
non-steroidal anti-inflammatory drug (NSAID)
alone or in combination for first-line management
of endometriosis-related pain.
ABOUBAKR ELNASHAR
43. If a trial of paracetamol or an NSAID (alone or in
combination) does not provide adequate pain relief:
consider other forms of pain management and
referral for further assessment.
ABOUBAKR ELNASHAR
44. Neuromodulators and neuropathic pain treatments
Offer a choice of amitriptyline, duloxetine,
gabapentin (Lyrica, Gapten)) or pregabalin as
initial treatment for neuropathic pain
Treatments to reduce central sensitization are
required in some patients
Tricyclics and antiepileptics
Multidisciplinary approach
Physiotherapy
Psychological therapy
(Peters et al, 1992)
ABOUBAKR ELNASHAR
45. SURGERY
When endometriosis is identified at laparoscopy,
clinicians are recommended to surgically treat
endometriosis, as this is effective for reducing
endometriosis-associated pain, i.e. ‘see and treat’
(Jacobson et al.,2009)A
ABOUBAKR ELNASHAR
46. Consider both ablation and excision of peritoneal
endometriosis to reduce endometriosis-associated
pain
(Wright et al.,2005; Healey et al., 2010).C
Ovarian endometrioma:
cystectomy instead of drainage and coagulation,
{cystectomy reduces endometriosis-associated
pain}
(Hart et al., 2008). A
cystectomy rather than CO2 laser vaporization
{lower recurrence rate}
(Carmona et al., 2011). B
ABOUBAKR ELNASHAR
47. Deep endometriosis
Consider surgical removal
{reduces endometriosis-associated pain and
improves quality of life}
(DeCicco et al., 2011; Meuleman et al., 2011a, b).B
Refer women with suspected or diagnosed deep
endometriosis to a centre of expertise that offers
all available treatments in a multidisciplinary
context. GPP
As an adjunct to surgery for deep endometriosis
involving the bowel, bladder or ureter, consider 3
months of gonadotrophin-releasing hormone
agonists before surgery.
ABOUBAKR ELNASHAR
48. HYSTERECTOMY.
with removal of the ovaries and all visible
endometriosis lesions in
women who have completed their family and
failed to respond to more conservative treatments.
Women should be informed that
hysterectomy will not necessarily cure the
symptoms or the disease.
GPP
ABOUBAKR ELNASHAR
49. laparoscopic uterosacral nerve ablation (LUNA)
Not perform
as an additional procedure to conservative surgery
to reduce endometriosis-associated pain
(Proctor et al., 2005).A
Presacral neurectomy (PSN)
effective as an additional procedure to
conservative surgery to reduce endometriosis-
associated midline pain
requires a high degree of skill
potentially hazardous procedure
(Proctor et al., 2005).A
ABOUBAKR ELNASHAR
50. Hysterectomy in combination with surgical
management (NICE, 2017)
If hysterectomy is indicated
woman has adenomyosis or
heavy menstrual bleeding that has not responded
to other treatments:
excise all visible endometriotic lesions at the
time of the hysterectomy.
Perform hysterectomy (with or without oophorectomy)
laparoscopically when combined with surgical
treatment of endometriosis, unless there are
contraindications.
ABOUBAKR ELNASHAR
51. For women thinking about having a hysterectomy,
discuss:
what a hysterectomy involves and when it may be needed
the possible benefits and risks of hysterectomy
the possible benefits and risks of having oophorectomy at
the same time
how a hysterectomy (with or without oophorectomy) could
affect endometriosis symptoms
that hysterectomy should be combined with excision of all
visible endometriotic lesions
endometriosis recurrence and the possible need for further
surgery
the possible benefits and risks of hormone replacement
therapy after hysterectomy with oophorectomy
ABOUBAKR ELNASHAR
52. Prevention of adhesion during laparoscopy
oxidized regenerated cellulose
Beneficial
(Ahmad et al., 2008). B
Icodextrin
no benefit
(Brown et al., 2007; Trew et al., 2011). B
other anti-adhesion agents
polytetrafluoroethylene surgical membrane
hyaluronic acid products:
effective for adhesion prevention in the context
of pelvic surgery, although not specifically in
women with endometriosis.
GPP
ABOUBAKR ELNASHAR
53. Preoperative hormonal therapies effective for
treatment of pain?
No
(Furness et al., 2004).A
Clearly distinguish
adjunctive short-term (≤6 months) hormonal
treatment after surgery from
long-term (≥6 months) hormonal treatment; the
latter is aimed at secondary prevention. GPP
not prescribe adjunctive hormonal treatment in
women with endometriosis for endometriosis-
associated pain after surgery, as it does not
improve the outcome of surgery for pain
(Furness et al., 2004).A
ABOUBAKR ELNASHAR
54. Secondary prevention of disease and painful
symptoms in women treated for endometriosis
defined as
interventions to prevent the recurrence of pain
symptoms or the recurrence of disease in the long-term,
defined as more than 6 months after surgery.
There is a role for prevention of recurrence of
disease and painful symptoms in women surgically
treated for endometriosis.
The choice of intervention depends on
Patient preferences
costs
availability
side effects.
For many interventions that might be considered here, there are limited data.
GPP
ABOUBAKR ELNASHAR
55. In women operated on for an endometrioma (≥3 cm):
ovarian cystectomy, instead of drainage and
electrocoagulation, for the secondary prevention of
endometriosis-associated dysmenorrhoea,
dyspareunia and non-menstrual pelvic pain
(Hart et al., 2008).A
After cystectomy for ovarian endometrioma in
women not immediately seeking conception:
COC for the secondary prevention of
endometrioma
(Vercellini et al., 2010).A
ABOUBAKR ELNASHAR
56. In women operated on for endometriosis:
post-operative use of a LNG-IUS or a
combined hormonal contraceptive
for at least 18–24 months
as one of the options for the secondary prevention of endometriosis-associated
dysmenorrhoea, but not for non-menstrual pelvic pain or dyspareunia
(Abou-Setta et al., 2006; Seracchioli et al., 2009). A
ABOUBAKR ELNASHAR
57. Extragenital endometriosis
can affect different tissues and body parts outside the genital tract.
Pain is the most common presenting symptom,
although a wide range of symptoms can manifest.
The evidence of the results of the different options to treat extragenital
endometriosis is limited and mainly published in case reports resulting in Level
D recommendations.
Consider surgical removal of symptomatic
extragenital endometriosis, when possible, to
relieve symptoms
(Liang et al., 1996; Marinis et al., 2006; Nisolle et al., 2007; Nissotakis et al.,
2010; Nezhat et al., 2011; Song et al., 2011). D
When surgical treatment is difficult or impossible:
medical treatment of extragenital endometriosis
to relieve symptoms
(Bergqvist, 1992; Joseph and Sahn, 1996; Jubanyik and Comite, 1997).
D
ABOUBAKR ELNASHAR
58. OTHER PAIN MANAGEMENT STRATEGIES
does not recommend the use of
nutritional supplements
complementary or alternative medicine
{potential benefits and/or harms are unclear}.
some women who seek complementary and
alternative medicine may feel benefit from this.
GPP
ABOUBAKR ELNASHAR
60. Mechanism of infertility
(Prentice, 2001)
I- Advanced disease:
Mechanical interference with
Ovulation
Ovum pick up
Tubo-ovarian adhesion
Distorted tubal anatomy.
ABOUBAKR ELNASHAR
61. II- Minimal & mild disease:
1. Coital problems: dysparunia.
2. Altered peritoneal environment:
increase
volume of peritoneal fluid
activated macrophages:
phagocytosis of sperms
decreased sperm motility
embyotoxicty
3. Altered foliccular maturation:
lutenized unruptured follicle
anovulation
luteolysis caused by prostaglandin F2
No evidence that they are more common in E.
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62. 1. Hormonal therapies
No need
For suppression of ovarian function to improve
fertility
(Hughes et al., 2007).{A}
hormonal contraceptives,
Progestagens
GnRH analogues or
Danazol
to improve fertility in minimal to mild endometriosis is not effective and
should not be offered for this indication alone.
The published evidence does not comment on more severe disease
(Hughes et al., 2007).
ABOUBAKR ELNASHAR
63. 2. Nutritional supplements, complementary
and alternative treatments
No evidence for a beneficial effect
(GPP)
ABOUBAKR ELNASHAR
64. 2. Surgery
Stage I/II:
•Operative laparoscopy:
excision or
ablation of the endometriosis lesions
adhesiolysis
rather than
•Diagnostic laparoscopy only, to increase PR
(Nowroozi et al., 1987; Jacobson et al., 2010).{A}
ABOUBAKR ELNASHAR
65. CO2 laser vaporization of endometriosis, instead of
monopolar electrocoagulation
{higher cumulative spontaneous PR }
(Chang et al., 1997).{C}
Offer excision or ablation of endometriosis plus
adhesiolysis for endometriosis not involving the
bowel, bladder or ureter, because this improves the
chance of spontaneous pregnancy.
ABOUBAKR ELNASHAR
66. Endometrioma
Excision of the capsule
instead of drainage and electrocoagulation of the
endometrioma wall
{increase spontaneous PR}
(Hart et al., 2008).{A}
ORT
If compromised: surgery is not recommended
Counseling:
Risks of reduced ovarian function after surgery
ABOUBAKR ELNASHAR
67. Stage III/IV
Operative laparoscopy, instead of expectant
management:
increase spontaneous PR
(Nezhat et al., 1989; Vercellini et al.,2006). {B}
Spontaneous PR of
(Olive et al., 1985; Nezhat et al., 1989; Vercellini et al., 2006).
After expectant
management
After operative
laparoscopy
Stage
33%52-68%III
0%57-69%IV
ABOUBAKR ELNASHAR
68. Hormonal treatment
Before surgery to improve spontaneous PR:
No
{evidence is lacking}
(GPP)
For pain
Yes
(GPP)
After surgery to improve spontaneous PR
No
(Furness et al., 2004).{A}
ABOUBAKR ELNASHAR
69. 3. IUI WITH COS
instead of expectant management
In Stage I/II
{increases LBR}
(Tummon et al., 1997).{C}
within 6 months after surgical TT:
{PR are similar to those achieved in unexplained
infertility }
(Werbrouck et al., 2006). {C}
ABOUBAKR ELNASHAR
70. 4. IVF
Indications
1. Age ≥38 y
2. Infertility is long lasting.
3. Diminished ovarian reserve
4. Tubal function is compromised
5. Male factor infertility
6. Bilateral endometriomas
7. Other treatments have failed.
8. Prior surgical treatment
In patients who failed to conceive spontaneously
after surgery: ART is more effective than repeat
surgery.
{GPP; Polat et al, 2015)
After surgery
{cumulative endometriosis recurrence rates are not increased after COS for IVF/ICSI}
(D’Hooghe et al., 2006; Benaglia et al., 2010;Coccia et al., 2010; Benaglia et al., 2011). {C}
ABOUBAKR ELNASHAR
71. Nonovarian disease:
Surgical resection
has not been consistently shown to improve
outcomes with the possible exception of resection of
deeply invasive disease, although the data is limited.
(Surrey, 2015)
ABOUBAKR ELNASHAR
72. Indications for Resection of a Suspected
Endometrioma prior to IVF
(Surrey et al, 2015)
1. Rapid growth
2. Suspicious features noted on ultrasound
3. Painful symptoms that can be attributed to the
mass
4. Potential for rupture in pregnancy
5. Inability to access follicles in normal ovarian
tissue.
ABOUBAKR ELNASHAR
73. Deep endometriosis
The effectiveness of surgical excision is
not well established with regard to reproductive
outcome
(Bianchi et al.,2009; Papaleo et al., 2011).{C}
ABOUBAKR ELNASHAR
74. GnRHa for a period of 3–6 months prior to treatment
with ART: improve PR
(Sallam et al., 2006). {B}
ORT: compromised
Long agonist protocol
A benefit (which did not reach clinical significance)
only when fresh and cryopreserved embryo transfers were combined.
(Houwen et al, 2014)
Significant benefit was noted only among patients stages III and IV
(Rickes et al, 2002)
ABOUBAKR ELNASHAR
78. 1. MENOPAUSE IN WOMEN WITH ENDOMETRIOSIS
In women with surgically induced menopause
because of endometriosis:
oestrogen/progestagen therapy or tibolone can be
effective for the treatment of menopausal
symptoms
(Al Kadri et al., 2009). B
continue to treat at least up to the age of natural
menopause.
ABOUBAKR ELNASHAR
79. Post-menopausal women after hysterectomy and with
a history of endometriosis:
avoid unopposed oestrogen treatment.
However, the theoretical benefit of avoiding disease
reactivation and malignant transformation of residual disease
should be balanced against the increased systemic risks
associated with combined oestrogen/progestagen or tibolone.
GPP
ABOUBAKR ELNASHAR
80. 2. ASYMPTOMATIC ENDOMETRIOSIS
should not routinely perform surgical excision and
ablation for an incidental finding of asymptomatic
endometriosis at the time of surgery, since the natural
course of the disease is not clear.
GPP
fully inform and counsel women about any incidental
finding of endometriosis
ABOUBAKR ELNASHAR
81. 3. PRIMARY PREVENTION OF ENDOMETRIOSIS
The usefulness of oral contraceptives for the primary
prevention of endometriosis is uncertain
(Vercellini et al., 2011). C
The usefulness of physical exercise for the primary
prevention of endometriosis is uncertain
(Vitonis et al., 2010). C
ABOUBAKR ELNASHAR
82. 4. ENDOMETRIOSIS AND CANCER
no evidence that endometriosis causes cancer
no increase in overall incidence of cancer in women
with endometriosis
some cancers
ovarian cancer and
non-Hodgkin’s lymphoma are slightly more
common in women with endometriosis.
explain the incidence of some cancers in women with endometriosis in absolute numbers.
no change in management of endometriosis in
relation to malignancies, since there are no clinical
data on how to lower the slightly increased risk of
ovarian cancer or non-Hodgkin’s lymphoma in women
with endometriosis.
GPP
ABOUBAKR ELNASHAR
83. You can get this lecture from:
1.My scientific page on Face book:
Aboubakr Elnashar Lectures.
https://www.facebook.com/groups/2277
44884091351/
2.Slide share web site
3.elnashar53@hotmail.com
4.My clinic: Elthwara St. Mansura
ABOUBAKR ELNASHAR