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Endometriosis
Dr Cathy Burke
MSc ProgrammeNovember 2009
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Endometriosis
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IntroductionOverview
Outline current treatment modalities
Explore evidence base for treatments
Present recommendations
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DefinitionThe presence of endometrial glands and
stroma outside the uterine cavity
endometrial glands
endometrial stroma
fibrosis
haemorrhage
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PrevalenceWomen with pelvic pain have a higher
incidence of endometriosis (range: 4080%)
than women with infertility without pain (2050%) or control groups (520%)
Koninckx et al, 1991
Prevalence increasing over the yearsGuo et al Gynecol Obstet Invest 2006
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PathologyPeritoneal inflammation and fibrosis
Adhesions
Ovarian cysts
Deep nodules
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SymptomatologyDysmenorrhea
Dyspareunia
Dyschezia / bowel symptoms / rectal bleeding
Non-cyclical pelvic pain
Urinary symptoms / haematuria
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AssociationsMenorrhagia (adenomyosis)
Subfertility
IBS
PID Seaman et al BJOG 2008
Chronic pain syndromesDepression - 86% vs 38%Lorencatto et al Acta Obsstet Gynecol Scand 2006
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PathogenesisRetrograde menstruation / transplantation Sampson
Coelomic metaplasia Meyer
Metastasis (haematogenous / lymphatic) Javert
Genetic basis (Chr 7, 10, 20) Montgomery et al Hum Reprod 08
Immunologic basis
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Susceptibility Genetic predisposition
Increased exposure to menstrual debris
Abnormal eutopic endometrium
Altered peritoneal environment
Reduced immune surveillance
Increased angiogenic capacity
Healy et al 1998; Vinatier et al 2001; Treloar et al 2002; Varma et al 2004
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Natural historyLargely unknown
Average sx duration 7 yrs prior to diagnosis
Remitting / recurring
Hormonally-driven
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Lifetime experience
Symptom duration 16 years
Half tried three / more medical treatments
Half had surgical procedures performed at least3 times
One in five had hysterectomy / oophorectomy -most successful for sxs
Sinaii et al Fertil Steril 2007, 1998 Endometriosis Association Survey
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Symptom-to-diagnosis lag
Confusion with other conditions
Co-existence with other conditions
Lack of awareness of and enquiry intosymptomatology
Un / Mis - diagnosed at laparoscopy
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Mechanisms of pain
Inflammatory cytokines in the peritonealcavity
Focal bleeding from implants
Irritation and direct infiltration of nerves
Hormonal modulation: pain threshold
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Mechanisms of subfertility
Distorted adnexal anatomy
Ovarian cysts
Adverse effects on folliculogenesis
Interference with oocyte/sperm survival,fertilization and embryogenesis
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Endometriosis - diagnosis
Quick
Time and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime and aTIFF (Uncompressed) decompressor
are needed to see this picture.
QuickTime and aTIFF (Uncompressed) decompressor
are needed to see this picture.
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VESICULARLESIONS
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PERITONEAL LESIONWITH
NEOVASCULARISATION AND FIBROSIS
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VESICULAR LESIONS
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TUBAL ENDOMETRIOSIS
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KISSING OVARIES
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PERITONEAL SCARRING
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SUBDIAPHRAGMATIC ENDOMETRIOSIS
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SUBDIAPHRAGMATIC SCARRING
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ADHESION-LIKE APPEARANCE
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RECTUM ADHERENTTO POD
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Endometriosis - locationOvaries 60%
Tubes 21%
POD / pelvic sidewall 83%
Ureter 13%
Bowel 51%
Bladder 13%
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Grading of
endometriosis
American Society forReproductive Medicine(ASRM)
Peritoneal disease
Ovarian disease
POD disease Adhesions
Stage I-IV
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Endometriosis -
Grade vs Symptoms
Grade not directly correlated with
symptomatology
Advanced disease more frequently related todysmenorrhea and dyspareunia compared to
early diseaseMilingos et al Gynaeol Obstet Invest 2006
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Endometriosis - what is the
impact?Quality of life(EuroQOL, Health score, EHPQ-30)
Social functioning(SF36/12)
Sexual activity(SAQ)
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Medical treatment
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Medical management
Non-steroidal anti-inflammatory drugs
Inhibition of ovulationOCP
GnRH agonists
Depo-Provera
Atrophy of endometriotic lesions / local effectOral progestogens
Depo-provera
Mirena
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Oral analgaesics
NSAIDS inconclusive evidence for useAllen et al, Cochrane review 2005
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Oral contraceptive pill
OCP effective for dysmenorrhea and reduced
endometrioma size
Harada et al Fertil Steril 2007
OCP equivalent to GnRHCochrane Review 2007
Continuous OCP in women in whom recurrent
dysmenorrhea not controlled by cyclical OCPVercellini et al Fertil Steril 2003
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GnRH agonistsGnRH agonist use for endometriosis-related
pain well-established
Dlugi et at Fertil Steril 1990,W
aller et al Fertil Steil 1993, Henzl et alNEJM 1988
GnRH agonists with or without add-back Ework better than OCP for post-surgicalrelapse. Add-back improves QOL scores
Zupi et al Fertil Steril 2004
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ProgestogensOral progestogens poorly tolerated due to side-
effects
Depo-provera equivalent to GnRH for pain scores.
Less loss of bone mineral density with DMPASchlaff et al Fertil Steril 2006
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Mirena70% symptomatic relief after 12 months
Vercellini et al 1999
Radiographic evidence of regression of rectovaginallesions
Fedele et al 2001
Improvement in severity and frequency of pain andmenstrual sxs, and staging of diseaseLockhat et al Hum Reprod 2004
Mirena equivalent to GnRH for pain
Petta et al Hum Reprod 2005
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Surgical treatment
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Surgery for endometriosis
Ablation / excision of superficial peritonealdeposits
Excision of deep peritoneal deposits
Stripping / drainage and ablation of
endometriomata
Hysterectomy / Oophorectomy
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Evidence for surgical treatment
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Ablation of endometriosis
Laser ablation superior to expectant mgt 62% vs25% clinical response at 6/12
Sutton et al Fertil Steril 1994
Helica thermal coagulation - 87% response at 6/12
Nardo et al Fertil Steril 2005
LUNA has no effect on endometriosis-relateddysmenorrhea
Vercellini et al Fertil Steril 2003
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Excision of deep endometriosis
Lap excision superior to placebo for pain and QOLAbbott et al Fertil Steril 2004
Symptoms, QOL and sexual function improved after
excisional surgeryGarry et al, Anaf et al, Redwine et al, Ford et al, Lyons et al, Dubernard et al,
Wykes et al
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Treatment of endometriomas
Stripping vs drainage and ablation of
endometriomas reduces pain symptoms
and recurrenceHart et al Fertil Steril 2005, Cochrane Review
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Hysterectomy / Oophorectomy
Hysterectomy associated with high rate ofsymptom resolution and low re-operation
rateShakiba et al Obstet Gynecol 2008
Ovarian conservation associated with
increased risk of recurrent pain (x 6) and re-operation rate (x 8)
Namnoun et al Fertil Steril 1995
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omplications of surgery
Complications of laparoscopy
Organ injury
ureter
bowel
bladder
Bleeding
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Adhesion prevention in
endometriosis surgerySuturing of ovary decreases adhesion formationPellicano et al Fertil Steril 2008
Adhesion prevention agents
Barrier Interceed reduces adhesionsCochrane 2008
Fluid Limited evidenceCochrane 2006
Icodextrin 4% (Adept) reduces adhesions
Brown et al Fertil Steril 2007
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Surgery - outcomesMean pre-op
VAS scores
Mean post-op
VAS scores
(Med FU 6/12)
Improvement
in mean
scores
p-value
Period pain 8 4.5 2.5
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Evidence for surgery
Pain and QOLImprovement in pain, SAQ and QOL scores up
to 5 years Placebo response rate 30%
Non-responsiveness to surgery 20%
Ford et al 2004; Abbott et al 2003 & 2005
LUNA is not effective in this groupJohnson et al 2005
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Evidence for surgery - FertilityLaparoscopic ablation of minimal/mild endo
improves fertilityMarcoux et al NEJM 1997, Cochrane Review 2002
Endometrioma excision
Ovulation rate in natural cycles reducedcompared with pre-opHorikawa et al, J Assist Reprod Genet 2008
Ovarian response in IVF-ET cycles reducedYazbeck et al, Gynecol Obstet Fertil 2006
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Post-operative treatment
Post-op continuous OCP and POP usefulRazzi et al Eur J Obstet Gynaecol Rep Biol 2007
Postoperative GnRH improved pain when usedfor 3/12 and 6/12
Parazzini et al Am J Obstet Gynecol 1994, Vercellini et al BJOG 1999
Post-op Mirena usefulAbbou Setta et al Cochrane Review 2006
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Post-operative treatment
Post-operative hormonal suppression (COCP or
GnRH) reduces dysmenorrhea vs placebo
Dietary supplementation improves non-
menstrual pain post-operatively as much as
OCP
Quality of life scores better with hormonal
suppressionSesti et al Fertil Steril 2007
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Endometriosis recurrence
30% recurrence of endometriomata 2 years
after surgical excisionKoga et al Hum Reprod 2006
Re-operation rate 35% after 3 yearsAbbott et al 2005
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Multidisciplinary management
of endometriosisAssociated with decrease in pain, anxiety,
depression in CPP groupKames et al Pain 1990
Integrated approach improved painsignificantly more than standard
approach with CPPPeters et al Obstet Gynecol 1991
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Complementary therapies
and endometriosisAcupuncture;
Japanese-style acupuncture vs sham acupunctureWayne et at J Paed Adolesc Gynecol
Shu Mu vs standard vs danazol on clinical sxs andCA125
Sun et al, Zhongguo Zhen Jiu 2006
Traditional Chinese medicine;
Neiyi pill / enema vs danazol x 3/12 on CA125levels
Lu et al Zhongguo Zhen Jiu, 2007
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ESHRE guideline
Laparoscopy desirable for women presenting
with sxs of endometriosis
Therapeutic trial of hormonal agents may be
used first line
Laparoscopically-diagnosed endometriosis
treated for 6/12 with ovarian suppression
drug
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ESHRE guideline
Inconclusive evidence that NSAIDS (Naproxen)efffective
Suppression of ovarian function for 6/12 reducesendometriosis-related pain. All hormonal drugsequally effective but side-effect and cost profilesdiffer
LNG-IUS reduces pain
GnRH treatment for up to 2 years with E/P addback
acceptable
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ESHRE guideline
Ideal practice is to diagnose and removeendometriosis at the same time provided consent hasbeen obtained
Ablation of endometriosis reduces pain, less so withmild disease
No evidence that LUNA is effective
Excision of deeply-infiltrating lesions reduces pain
Severe / deeply infiltrating endometriosis should bereferred to a centre with ex ertise
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ESHRE guideline
Suppression of ovarian function not effective
to enhance fertility
Insufficient evidence that excision ofmoderate-severe endometriosis enhances
pregnancy rates
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Future treatments for
endometriosisPresacral neurectomy
Mifepristone (anti-progesterone)
Aromatase inhibitors (anastrozole,
letrozole)
TNF alpha inhibitors
Thalidomide
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THANK YOU