Overview of Reviews

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Endometriosis: an overview of Cochrane Reviews

  1. Julie Brown1,*,
  2. Cindy Farquhar2

Editorial Group: Cochrane Gynaecology and Fertility Group

Published Online: 10 MAR 2014

Assessed as up-to-date: 6 MAR 2014

DOI: 10.1002/14651858.CD009590.pub2


How to Cite

Brown J, Farquhar C. Endometriosis: an overview of Cochrane Reviews. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No.: CD009590. DOI: 10.1002/14651858.CD009590.pub2.

Author Information

  1. 1

    The University of Auckland, Liggins Institute, Auckland, New Zealand

  2. 2

    University of Auckland, Department of Obstetrics and Gynaecology, Auckland, New Zealand

*Julie Brown, Liggins Institute, The University of Auckland, Park Rd, Grafton, Auckland, 1142, New Zealand. j.brown@auckland.ac.nz.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 10 MAR 2014

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Table 1. Details of reviews

Review IDDate assessed as up to dateNumber of included trialsNumber of participantsInterventionControl or comparison interventionOutcomes for which data assessedReview limitations

GnRH agonist/antagonist

Sallam 200617/10/20083 RCTs165 womenLeuprolide acetate 3.75mg

 

Triptorelin 3.75mg
No treatment

 

Leuprolide acetate 0.5 to 1.0mg

 

GnRH agonist 3.75mg
Clinical pregnancy

 

Dose of FSH/HMG

 

Duration of FSH

 

Number of oocytes retrieved

 
Only 3 trials

 

Trials lacked details of  allocation concealment

 

No blinding

Brown 201027/09/201042 RCTs4935 womenAny GnRHaNo treatment

Placebo

Danazol

Intrauterine progesterone devices

Another GnRHa
Pain relief

Adverse effects

Resolution of endometriosis

Quality of life

Additional use of analgesia
The trials were limited by lack of adequate information on randomisation, allocation concealment and blinding

Benschop 201004/10/20104 RCTs312 womenSurgical or medical therapy prior to treatmentPlacebo

No treatment

Other surgical or medical therapy
Clinical pregnancy rate

Live birth

Adverse events

Quality of life

Pain

Recurrence

Estrodial levels

Number of mature oocytes
No live birth reported in the included trials. Overall trials well conducted but two of the trials did not conduct any blinding

Ovarian suppression

Hughes 200719/04/2009 (stable review no longer being updated)25 RCTs2600 womenDienogest

 

Triptorelin

 

MPA

 

Leuprolide acetate

 

Nafarelin

 

Provera

 

Goserelin

 

Danazol

 

Mestronol

 

Gestrinone

 

Buserelin

 
Triptorelin

 

Expectant management

 

Placebo

 

No treatment

 

Nafarelin

 

Danazol
Live birth

 

Clinical pregnancy
Only 2 trials reported live birth

 

The majority of the trials included in the review lacked details on randomisation and allocation concealment and there was limited blinding of allocation

Davis 200717/05/20071 RCT57 womenLow dose oral contraceptive (0.02mg ethinyl estradiol with 0.15mg desogestrel taken cyclically)Monthly goserelin 3.6mg subcutaneousPain

Satisfaction

Withdrawal

Side effects

Economic evaluation
The trial included in the review lacked details on randomisation and allocation concealment, there was no blinding and evidence was based on a single trial

Abou-Setta 201313/6/20123 RCTs135 womenLNG-IUDExpectant managementPain

Satisfaction

Dropout rates
There was no evidence of blinding in two of the trials

Al-Kadri 200910/07/20082 RCTs193 womenEstrogen, with or without progesteronePlacebo

Tibolone
Pain

Disease recurrence
There was no evidence of blinding and the trials lacked precision

Farquhar 200715/06/2007 (stable review, no longer being updated)5 RCTs370 womenDanazol 600 mg dailyMPA 100mg

Placebo

No treatment
Pain

AFS score

Pregnancy

Side effects

Symptoms

Hormone level

Biochemical markers
There was a lack of evidence for randomisation and allocation concealment in many of the included trials and four of the trials were open label

Brown 201217/01/201113 RCTs1511 womenMedroxyprogesterone PO/depot/sc

Gestrinone 2.5mg

Dienogest 2mg

Dydrogesterone 40/60 mg

Cyproterone acetate 12.5mg
Nafarelin 200 ug IN

Danazol 400mg/ 600mg

Leuprolide 3.75mg/ 11.25mg IM

Buserelin 300ug IN

Oral contraceptive

Placebo
Pain scores

rAFS

Side effects

Fertility

Bone mineral density

Lipid profiles

Biochemical measures

Quality of life

Analgesics

Allen 200923/04/20082 RCTs48 womenIndomethecin 25mg

Acetylsalictyic acid 500mg

Tolfenamic acid 200mg

Naproxen 275mg
PlaceboPain

Side effects

Effects on activities of daily living

Additional medication use
Trials lacked detail on allocation concealment and randomisation methods and one of the trials lacked details on blinding

Surgical

Benschop 201004/10/20104 RCTs312 womenSurgery (aspiration or cystectomy)Expectant managementClinical pregnancy rate

Live birth

Adverse events

Quality of life

Pain

Recurrence

Estrodial levels

Number of mature oocytes
No live birth reported in the included trials. Overall trials well conducted but two of the trials did not conduct any blinding

Duffy 201431.7.1310 RCTs973 womenLaparoscopic surgeryAny other laparoscopic or robotic intervention, holistic or medical treatment or diagnostic laparoscopy onlyOverall pain

Live birth

Specific types of pain

Clinical pregnancy

Adverse events
Common limitations in the primary studies included lack of clearly-described blinding, failure to fully describe methods of randomisation and allocation concealment, and risk of attrition bias

Hart 200831/08/20092 RCTsNot detailed in reviewExcisionDrainage and ablationPelvic pain

 

Spontaneous conception

Recurrence of endometrioma

 

Requirements for further surgery

 

Conversion to laparotomy

 

Pregnancy rate

 

Ovarian response to stimulation

 

 

 

 

 
No reporting of live birth

 

Studies lacked details on blinding but otherwise methodologically sound

Pre or post-surgical medical therapy

Furness 200420/09/2010 9 RCTS 769 womenPost-surgical triptorelin 3.75mg 

Danazol 600mg

Leuprolide acetate 3.5mg

Triptorelin 3.75mg

Nafarelin 400 µg

MPA 100mg

Goserelin 3.6mg

Gestrinone 2.5 mg
Pre and post-surgical triptorelin

No treatment/placebo
PregnancyLive birth not reported

Lu 201220/03/20124 RCTs334 womenLaparoscopic surgery + PentoxifyllineLaparoscopic surgery alone or + PlaceboReduction in pain

 

Clinical pregnancy

 

Recurrence rates
Live birth not reported

 

Only two trials adequately reported allocation concealment.  Only one trial reported blinding. All of the trials lacked adequate information on addressing incomplete outcome data

Other

Lu 20133/9/121 RCT21 womenAnti-TNF-αPlacebo

No treatment

Medical treatment

Surgical treatment
Biberoglu and Behrman score

Visual analogue pain score

Use of analgesics
Did not conduct ITT analysis

Flower 201231/10/20112 RCTs158 women Chinese herbal medicine Gestrinone or

Danazol or

other Chinese herbal medicine 
Pregnancy rate

Symptomatic relief

Dysmenorrhoea score

Rectal irritation relief

Tenderness of vaginal nodes

Adnexal masses, tenderness or shrinkage
No live birth reported. Evidence is based on single trials. 

Zhu 201127/7/20101 RCT67 womenAcupunctureChinese herbal medicine"cured" of painThere was a lack of adequate explanation for randomisation and allocation concealment and there were no details on blinding

Furness 200420/09/201010 RCTs1046 womenPost-surgical triptorelin 3.75mg 

Danazol 600mg

Leuprolide acetate 3.5mg

Triptorelin 3.75mg

Nafarelin 400 µg

MPA 100mg

Goserelin 3.6mg

Gestrinone 2.5 mg
Pre and post-surgical triptorelin

No treatment/placebo
Pain, recurrenceMost of the included trials lacked adequate methodological detail and there was a lack of blinding

 
Table 2. Description of populations in included reviews

Review authorAge (years)Stage of disease

Abou-Setta 2013No details in reviewEligible participants were women with any stage of endometriosis who had undergone any type of surgical treatment for endometriosis that preserved their uterus, with surgery no more than three months prior to randomisation.

One trial included women with moderate to severe endometriosis and one trial included only women with severe endometriosis. The third trial included women with moderate to severe endometriosis-related pain who were scheduled for laparoscopic surgery.

Allen 2009Mean age 33 yearsEligible participants were women with any stage or severity of endometriosis. Endometriosis was diagnosed by visualisation (for example laparoscopy or laparotomy) or was a suspected diagnosis based on the history and pelvic examination and other tests such as ultrasound, MRI, and the CA-125 blood test.

Al-Kadri 2009No details in reviewEligible participants were women with ectopic endometrial tissue that potentially could lead to distressing and debilitating symptoms regardless of the size and site of the deposits.

Benschop 2010Women with age ranging from 25 to 36 yearsEligible participants were women with endometriomata who underwent surgical, medical or combination treatment or expectant management prior to ART. The endometriomata were diagnosed by laparoscopy or imaging tests such as ultrasound and magnetic resonance imaging (MRI).

The women in the included studies had endometriomata ranging in size from ≥ 1.28cm to < 6 cm.

Brown 2010All participants were pre-menopausalEligible participants were pre-menopausal women with symptoms ascribed to endometriosis. The clinical diagnosis of endometriosis had to be made by direct visualisation (laparoscopy). Studies were included irrespective of the duration of symptoms.

There were no details on stage of disease for 26 trials. Twelve trials reported including stages I to IV.

Brown 2012Women with age ranging from 18 to 49Eligible participants were women of reproductive years with painful symptoms and a laparoscopic diagnosis of endometriosis.

Davis 2007No details in reviewEligible participants were women of reproductive age who complained of symptoms ascribed to the diagnosis of endometriosis. The diagnosis must have been established during a surgical procedure performed prior to the start of treatment.

Duffy 2014No details in reviewEligible participants were women with endometriosis confirmed with a visual diagnosis at diagnostic or operative laparoscopy.

Farquhar 2007Four trials reported mean ages which ranged from 28.2 to 32.5 years, one trial reported women were aged <41 yearsEligible participants were women of reproductive age with the diagnosis of endometriosis made by direct visualisation (laparoscopy or laparotomy). This included women who were asymptomatic and where endometriosis was an incidental finding.

Four trials recruited women who mainly had a diagnosis of stage I to II disease, one trial recruited women with moderate to severe disease. Two trials appeared to have recruited women post-surgically

Flower 2012No details in reviewEligible participants were women of reproductive age with a laparoscopically confirmed diagnosis of endometriosis.

No further details in review

Furness 2004Women of reproductive age or <40 years were includedEligible participants were women of reproductive age who were undergoing surgery for endometriosis. The diagnosis of endometriosis could have been made provisionally by clinical examination and confirmed during the surgery, or could have been confirmed endometriosis where women were undergoing second or subsequent surgery. They would have further medical treatment either before or after surgery.

Two trials did not report on inclusion criteria for stage of disease but the remaining trials included women with AFS III to IV

Hart 2008No details in reviewEligible participants were women with ovarian endometriomata who were undergoing surgery for the indication of pain or infertility. Endometriomata were defined as cysts of endometriosis within the ovary.

Hughes 2007Range 18 to 45Eligible participants were women with visually diagnosed endometriosis, either by laparoscopy or laparotomy, who had failed to conceive after 12 or more months of unprotected intercourse. Trials where medical treatment was administered after surgical treatment for endometriosis were included.

The majority of included trials reported laparoscopically diagnosed endometriosis. Five trials reported including women with any stage of disease and eight trials reported including women with Stage III to IV endometriosis. Three trials included women with mild to moderate disease and the remaining trials did not report on this measure.

Lu 2012Mean ages in the intervention group ranged from 29.7±8.1 to 33.1±3.6; for the control group mean age ranged from 28.31±4.19 to 32.9±6.5 yearsEligible participants were premenopausal, subfertile women with visually diagnosed endometriosis, either by laparoscopy or on the basis of international guidelines used to diagnose endometriosis. Trials where medical treatment was administered after surgical treatment for endometriosis were included.

Three of the included studies recruited women with AFS I-II and one trial recruited women with Stage I-IV disease

Lu 2013Women aged 20 to 45 yearsEligible participants were pre-menopausal, subfertile women with visually diagnosed endometriosis, either by laparoscopy or on the basis of international guidelines used to diagnose endometriosis. Trials where medical treatment was administered after surgical treatment for endometriosis were included.

Women in the included study had deep endometriosis nodule of at least 1 cm in diameter and severe pain

Sallam 2006No details in reviewEligible participants were infertile women diagnosed with endometriosis and treated with IVF or ICSI. The diagnosis of endometriosis must have been based on laparoscopy or laparotomy

Zhu 2011Age range of participants 22 to 47 yearsEligible participants were women of reproductive age with a diagnosis of endometriosis confirmed laparoscopically. Participant exclusion criteria included primary dysmenorrhoea (the absence of an identifiable pathological condition) or asymptomatic endometriosis.

Women in the included study had all stages of disease from mild to severe

 
Table 3. AMSTAR assessment

Review noFirst authorREVIEW TITLEAMSTAR CRITERIA




Prespecified question and inclusion criteriaDuplicate study selection and data extractionComprehensive lit searchGrey lit includedLists included and excluded studiesDescribes characteristics of included studiesStudy quality assessedStudies combined using appropriate methodsLikelihood of publication bias considered/testedPotential for conflict of interest addressed

AMAS1061Abou-Setta 2013Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery

MCA871Allen 2009Non-steroidal anti-inflammatory drugs for pain in women with endometriosisx

HAK1181Al-Kadri 2009Hormone therapy for endometriosis and surgical menopausex

SG1241Benschop 2010Interventions for women with endometrioma prior to assisted reproductive technology

APO62Brown 2010Gonadotrophin-releasing hormone analogues for pain associated with endometriosis

AP061Brown 2012Progestagens and anti-progestagens for pain associated with endometriosis

SK141Davis 2007Oral contraceptives for pain associated with endometriosisx

JD1830Duffy 2014Laparoscopic surgery for endometriosis.

VS081Farquhar 2007Danazol for pelvic pain associated with endometriosisx

AF801Flower 2012Chinese herbal medicine for endometriosis

CY571Furness 2004Pre and post-operative medical therapy for endometriosis surgeryx

RJH961Hart 2008Excisional surgery versus ablative surgery for ovarian endometriomata

EJ254Hughes 2007Ovulation suppression for endometriosis for women with subfertility

DL1540Lu 2012Pentoxifylline for endometriosis

DD1570Lu 2013Anti-TNF-α treatment for pelvic pain associated with endometriosis

HNS881Sallam 2006Long term pituitary down-regulation before in vitro fertilisation (IVF) for women with endometriosisx

KRF1291Zhu 2011Acupuncture for pain in endometriosisx

 
Table 4. Search date assessment

Review noReview referenceREVIEW TITLE<3 yrs since last search

(to March 6 2014)

AMAS1061Abou-Setta 2013Levonorgestrel-releasing intrauterine device (LNG-IUD) for symptomatic endometriosis following surgery

MCA871Allen 2009Non-steroidal anti-inflammatory drugs for pain in women with endometriosis

HAK1181Al-Kadri 2009Hormone therapy for endometriosis and surgical menopause

SG1241Benschop 2010Interventions for women with endometrioma prior to assisted reproductive technology

APO62Brown 2010Gonadotrophin-releasing hormone analogues for pain associated with endometriosis

AP061Brown 2012Progestagens and anti-progestagens for pain associated with endometriosis

SK141Davis 2007Oral contraceptives for pain associated with endometriosis

JD1830Duffy 2014Laparoscopic surgery for endometriosis

VS081Farquhar 2007Danazol for pelvic pain associated with endometriosisStable

AF801Flower 2012Chinese herbal medicine for endometriosis

CY571Furness 2004Pre and post-operative medical therapy for endometriosis surgery

RJH961Hart 2008Excisional surgery versus ablative surgery for ovarian endometriomata

EJ254Hughes 2007Ovulation suppression for endometriosis for women with subfertilityStable

DL1540Lu 2012Pentoxifylline for endometriosis

DD1570Lu 2013Anti-TNF-α treatment for pelvic pain associated with endometriosis

HNS881Sallam 2006Long term pituitary down-regulation before in vitro fertilisation (IVF) for women with endometriosis

KRF1291Zhu 2011Acupuncture for pain in endometriosis

 
Table 5. Pain outcomes

Outcome

Intervention and comparison intervention
Illustrative comparative risks (95% CI)Relative effect

(95% CI)
Number of participants

(studies)
Quality of the evidence

(GRADE)
Comments







Assumed risk

with comparator
Corresponding risk

with intervention

Reduction in pain at 3 months

Lu 2012 Laparoscopic surgery plus pentoxifylline versus laparoscopic surgery plus placeboThe mean reduction in pain at 3 months in the laparoscopic surgery plus placebo groups was 5.53 (VAS score)The mean reduction in pain at 3 months in the laparoscopic surgery plus pentoxifylline groups was 1.6 lower (3.32 lower to 0.12 higher) (VAS score)-34 ( 1 study)Very lowLacked methodological detail, and lack of precision. Evidence based on a single study

Dysmenorrhoea

Duffy 2014

Laparoscopic excision versus diagnostic laparoscopy
At 6 months, the mean dysmenorrhoea pain score in the excision group was 2.4 higher than in the diagnostic laparoscopy group (6.18 lower to 10.98 higher) on a VAS 0-100 scale39 (1 study)LowVery serious imprecision - single small study, wide confidence intervals

Duffy 2014

Laparoscopic excision versus diagnostic laparoscopy
At 12 months, the mean dysmenorrhoea pain score in the excision group was 9.5 lower than in the diagnostic laparoscopy group (20.58 lower to 1.58 higher) on a VAS 0-100 scale39 (1 study)LowVery serious imprecision - single small study, wide confidence intervals

Furness 2004

Post-surgical medical therapy versus placebo
-The mean pain score (VAS) in the intervention group was 0.58 standard deviations lower than in the placebo group (0.87 to 0.28 lower)-187 (1 study)LowLacked sufficient details on allocation concealment and blinding

Flower 2012 Chinese herbal medicine Nei Yi pills versus danazol-The mean dysmenorrhoea score in the Chinese herbal medicine Nei Yi pills group was 1.01 lower (3.11 lower to 1.09 higher) than in the danazol group-34 ( 1 study)LowEvidence based on a single trial, quality of blinding very uncertain

Flower 2012 Chinese herbal medicine Nei Yi pills + Nei Yi enema versus danazol-The mean dysmenorrhoea score in the Chinese herbal medicine Nei Yi pills group was 2.9 lower (4.55 lower to 1.25 higher) than in the danazol group42 (1 study)LowEvidence based on a single trial, quality of blinding very uncertain

Flower 2012 Chinese herbal medicine Nei Yi pills + Nei Yi enema versus Nei Yi pillsThe mean dysmenorrhoea score in the Chinese herbal medicine Nei Yi pills + enema group was 1.89 lower (3.89 lower to 0.11 higher) than in the Nei Yi pills alone group-40 (1 study)LowEvidence based on a single trial, quality of blinding very uncertain

Brown 2010 GnRHas versus no treatment188/1000 achieved pain relief737/1000 achieved pain reliefRR 3.93 (1.37 to 11.28)35 (1 study)LowNo blinding and evidence based on a single trial

Brown 2010 GnRHas versus danazol825/1000 achieved pain relief809/1000 achieved pain reliefRR 0.98 (0.92 to 1.04)666 (7 studies)Very lowRandomisation and allocation concealment was inadequately reported in most of the trials. Blinding was unclear in two trials and there was no blinding in two trials. I2 was 44% which suggests some heterogeneity

Brown 2010 GnRHas (3 month versus 6 month)-The mean dysmenorrhoea score in the three month group was 0.02 standard deviations lower (0.31 lower to 0.27 higher) than in the six month group-179 (1 study)ModerateEvidence was based on a single trial

Brown 2010 GnRHas (intranasal versus intramuscular depot)828/1000 achieved pain relief778/1000 achieved pain reliefRR 0.94 (0.82 to 1.08)192 (1 study)LowLack of adequate explanation of allocation concealment and evidence based on a single trial

Brown 2010 GnRHas (intranasal versus subcutaneous)800/1000 achieved pain relief976/1000 achieved pain reliefRR 1.22 (0.73 to 2.06)10 (1 study)LowOpen label trial with evidence based on a single trial

Furness 2004

Pre-surgical medical therapy versus post-surgical medical therapy
See CommentSee CommentRR 0.0 (0 to 0)53 (1 study)LowThere were no events reported in either the intervention or the control group. There were insufficient methodological details for allocation concealment or randomisation

Davis 2007

Oral contraceptive versus goserelin
The mean dysmenorrhoea pain score in the control groups was 7.5The mean dysmenorrhoea pain score in the intervention groups was 0.10 lower (1.28 lower to 1.08 higher)-50 (1 study)Very lowThere was a lack of adequate explanation for allocation concealment, and randomisation. There was no blinding. The evidence was based on a single trial.

Lu 2013

Anti-TNF-α plus surgery versus placebo plus surgery - clinician score
The mean dysmenorrhoea Biberoglu and Behrman score in the control groups was 2.3The mean Biberoglu and Behrman score in the intervention groups was 0.2 higher (0.05 lower to 0.45 higher)-21 (1 study)LowEvidence based on a single trial and not ITT conducted.

Lu 2013

Anti-TNF-α plus surgery versus placebo plus surgery - patient score
The mean Biberoglu and Behrman score in the control groups was 1.7The mean Biberoglu and Behrman score in the intervention groups was 0.2 lower (0.68 lower to 0.28 higher)-21 (1 study)LowEvidence based on a single trial and not ITT conducted.

Brown 2012

Anti-progestagen versus other treatment (end of treatment)
The mean patient assessed efficacy at end of treatment in the control groups was 0.05The mean patient assessed efficacy at end of treatment in the intervention groups was 0.82 higher (0.15 to 1.49 higher)-55 (1 study)ModerateEvidence was based on a single trial

Brown 2012

Anti-progestagen versus other treatment (12 months)
The mean patient assessed efficacy at 12 months follow-up in the control groups was 4.76The mean patient assessed efficacy at 12 months follow-up in the intervention groups was 3 lower (4.79 to 1.21 lower)-55 (1 study)ModerateEvidence was based on a single trial

Brown 2012

Depot progestagen versus other treatment (6 months)
978/1000 achieved pain relief895/1000 achieved pain reliefOR 0.19 (0.05 to 0.69)274 (1 study)ModerateEvidence was based on a single trial

Brown 2012

Depot progestagen versus other treatment (12 months)
768/1000 achieved pain relief676/1000 achieved pain reliefOR 0.63 (0.37 to 1.08)274 (1 study)ModerateEvidence was based on a single trial

Brown 2012

Anti-progestagen versus other treatment
667/1000 achieved pain relief673/1000 achieved pain reliefOR 1.03 (0.55 to 1.93)176 (2 studies)ModerateTrials lacked details on randomisation. One trial appeared to have inadequate allocation concealment and no blinding

Pain score


Brown 2010

GnRHas versus placebo
-The mean overall pain score at 4 weeks in the intervention group was 2.9 higher (2.11 to 3.69 higher) than in the placebo group-120 (1 study)LowAllocation concealment and blinding were inadequately explained and the evidence was based on a single trial

Abou-Setta 2013

LNG-IUD versus GnRHa
The mean VAS score for painful symptoms in the control groups was 3.63The mean VAS score for painful symptoms in the intervention groups was 0.16 lower (2.02 to 1.7 higher)-40 (1 study)Very lowNo evidence of blinding in the included trial and evidence was based on a single trial. There was also imprecision in the summary statistic

Farquhar 2007

Danazol versus placebo (no surgery)
The mean pelvic pain score in the control groups was 1.85The mean pelvic pain score in the intervention groups was 1.4 lower (1.33 to 0.77 lower)35 (1 study)LowThere was a lack of adequate explanation for allocation concealment and randomisation and evidence was based on a single trial

Farquhar 2007

Danazol versus placebo (post-surgery) - pelvic pain 6 months
The mean pelvic pain score in the control groups was 1.55The mean pelvic pain score in the intervention groups was 1.1 lower (1.38 to 0.82 lower)34 (1 study)LowThere was a lack of adequate explanation for allocation concealment and randomisation and evidence was based on a single trial

Farquhar 2007

Danazol versus placebo (post-surgery) - pelvic pain 6 months
310/1000 had moderate or severe pelvic pain at 6 months226/1000 had moderate or severe pelvic pain at 6 monthsOR 0.65 (0.2 to 2.05)60 (1 study)LowThere was a lack of adequate explanation for allocation concealment and randomisation and evidence was based on a single trial

Lu 2013

Anti-TNF-α plus surgery versus placebo plus surgery - clinician score
The mean Biberoglu and Behrman score in the control groups was 1.45The mean Biberoglu and Behrman score in the intervention groups was 0.15 lower (0.45 lower to 0.15 higher)-21 (1 study)LowEvidence was based on a single trial. No ITT analysis conducted

Lu 2013

Anti-TNF-α plus surgery versus placebo plus surgery - patient score
The mean Biberoglu and Behrman score in the control groups was 0.15The mean Biberoglu and Behrman score in the intervention groups was 0.15 lower (0.51 lower to 0.21 higher)-21 (1 study)LowEvidence was based on a single trial. No ITT analysis conducted

Brown 2012

Oral progestagens versus other treatment (6 months)
The mean self-reported pain in the control group was 41.8The mean self-reported pain in the intervention group was 1.6 lower (0.01 lower to 0.57 higher)-252 (1 study)LowOpen label study with evidence based on a single trial

Supplementary analgesia use

Lu 2013

Anti-TNF-α plus surgery versus placebo plus surgery
The mean use of analgesia in the control group was 0.28The mean use of analgesia in the intervention group was 0.1 (0.6 lower to 0.4 higher)-30 (1 study)LowEvidence was based on a single trial. No ITT analysis conducted

Allen 2009

NSAIDS versus placebo
--OR (inverse variance) 0.12 (0.01 to 12.9)20 (1 study)Unable to conduct GRADE analysis as inverse variance used (no raw data)There was a lack of adequate explanation for allocation concealment, and randomisation. The evidence was based on a single trial

Disease recurrence/rAFS

Hart 2008

Excisional versus ablative surgery for endometriomata
262/1000128/1000OR 0.41 (0.18 to 0.93)164 (2 studies)Very lowIncluded studies lacked blinding

Furness 2004

Pre-surgical medical therapy versus no medical therapy
-The mean recurrence (AFS) score was 9.6 lower (11.42 to 7.78 lower) in the intervention group-80 (1 study)LowNo blinding and trial lacked details on allocation concealment

Furness 2004

Post-surgical medical therapy versus pre and post-surgical medical therapy with GnRHa
-The mean recurrence (AFS) score was 3.49 higher (5.1 to 12.08 higher) in the intervention group-25

(1 study)
Very lowLacked sufficient detail on randomisation and allocation concealment and there was a lack of precision

Furness 2004

Post-surgical medical therapy versus placebo
-The mean recurrence (AFS) score was 2.29 lower (4.69 lower to 0.11 higher) in the intervention group-43 (1 study)LowLacked sufficient detail on randomisation and allocation concealment

Brown 2010

GnRHas versus danazol
-The mean rAFS in the intervention groups was 0.01 standard deviations lower (0.13 to 0.12)-1012 (10 studies)LowThere was a lack of adequate explanation for randomisation and allocation concealment and blinding

Brown 2010 GnRHas (400 mcg versus 800 mcg)200/100082/1000RR 0.41 (0.17 to 1.01)143 (1 study)LowLack of adequate explanation for randomisation, allocation concealment and blinding. Evidence was based on a single trial

Brown 2010 GnRHas versus intrauterine progestagen device-The mean rAFS score in the intervention groups was 9.5 higher (10.77 lower to 29.77 higher)-18 (1 study)LowOpen label study with no blinding and evidence based on a single trial

Brown 2010 GnRHas (intranasal versus subcutaneous)-The mean rAFS score in the intervention groups was 9 higher (5.93 lower to 23.93 higher)-19 (1 study)Very lowLacked an adequate explanation of allocation concealment and randomisation and blinding. Evidence based on a single trial

Al-Kadri 2009

Estrogen, with or without progesterone versus placebo
0/10000/1000OR 2.53 (0.12 to 53.64)172 (1 study)Very lowThere was no evidence of blinding , there was imprecision and the evidence was based on a single trial

Farquhar 2007 Danazol versus placebo (no surgery)The mean change in total AFS scores in the control group was 0.2The mean change in total AFS scores in the intervention group was 1.9 lower (4.16 lower to 0.36 higher)-31 (1 study)Very lowLacked an adequate explanation of randomisation and allocation concealment and the evidence was based on a single trial

Farquhar 2007 Danazol versus placebo (post-surgery)The mean change in total AFS scores in the control group was -4.5The mean change in total AFS scores in the intervention group was 0.9 lower (3.02 lower to 1.22 higher)-27 (1 study)Very lowLacked an adequate explanation of randomisation and allocation concealment and the evidence was based on a single trial

Brown 2012

Anti-progestagen versus other treatment
The mean AFS score in the control group was 11.8The mean AFS score in the intervention group was 1.4 higher (6.76 lower to 9.56 higher)-16 (1 study)Very lowThe single trial was open label and appeared to have inadequate allocation concealment

Brown 2012

Oral progestagens versus other treatment
The mean change in AFS scores in the control group was 1.31The mean AFS score in the intervention group was 0.34 higher (0.01 lower to 0.70 higher)-302 (1 study)ModerateThere was an inadequate explanation of allocation concealment, randomisation and blinding

Brown 2012

Progestagen versus placebo
Mean AFS score in the control group was 1.76Mean AFS score in the intervention group was 0.58 lower (1.41 lower to 0.25 higher)-33 (1 study)LowThis single trial provided inadequate detail on allocation concealment and blinding

Resolution of pain

Zhu 2011 Acupuncture versus Chinese herbal medicine267/1000811/1000RR 3.04 (1.65 to 5.62)67 (1 study)Very lowLack of methodological detail. No blinding and evidence based on single study.

Brown 2010 GnRHas versus danazol596/1000655/1000RR 1.1 (1.01 to 1.21)1046 (9 studies)LowThere was a lack of adequate detail for randomisation and allocation concealment and blinding. Two trials had no blinding

Brown 2010 GnRHas versus intrauterine progestagen device (LNG-IUD)-The mean relief of painful symptoms in the intervention group was 0.25 standard deviations lower (0.6 lower to 0.1 higher)-129 (3 studies)ModerateThere was a lack of blinding and inadequate explanation of allocation concealment

Brown 2010 GnRHas (400mcg versus 800mcg)356/1000334/1000RR 0.94 (0.53 to 1.66)90 (1 study)ModerateEvidence based on a single trial

Davis 2007

Oral contraceptive versus goserelin
818/1000774/1000OR 0.76 (0.17 to 3.29)44 (1 study)Very lowThere was a lack of adequate explanation for allocation concealment, and randomisation. There was no blinding. The evidence was based on a single trial

Duffy 2014

Laparoscopic ablation or excision
321 per 1000 improved or better at 6 months756 per 1000 improved or better at 6 months (610 to 861)OR 6.58 (3.31 to 13.10)171 (3 studies)ModerateNone of studies blinded participants, only one fully described methods of randomisation and allocation concealment

Duffy 2014

Laparoscopic ablation or excision
214 per 1000 improved or better at 12 months732 per 1000 improved or better at 12 months (467 to 895)OR 10.00 (3.21 to 31.17)69 (1 study)LowOnly conference abstract available: randomisation methods not fully described, high risk of attrition bias, unclear whether blinded; single small study

Duffy 2014

Laparoscopic surgery versus laparoscopic surgery plus medical therapy
167 per 1000 pain free at 12 months530 per 1000 pain free at 12 months (191 to 843)OR 5.63 (1.18 to 26.8535 (1 study)LowOnly conference abstract available: randomisation methods not fully described, unclear whether blinded; single small study

Allen 2009

NSAID versus placebo
--OR (inverse variance)

0.327 (0.61 to 17.69)
20 (1 study)Unable to conduct GRADE analysis as inverse variance used (no raw data)There was a lack of adequate explanation for allocation concealment, and randomisation. The evidence was based on a single trial

Brown 2012

Anti-progestagen versus other treatment
667/1000673/1000OR 1.03 (0.55 to 1.93)176 (2 studies)LowTwo trials lacked details on randomisation. One of the trials appeared to have inadequate allocation concealment and no blinding

Pain recurrence up to 1 year

Furness 2004

Post-surgical medical therapy versus placebo
273/1000207/1000RR 0.76 (0.52 to 1.1)332 (3 studies)LowLacked sufficient evidence for allocation concealment or attrition and there was no blinding

Abou-Setta 2013

LNG-IUD versus expectant management
383/100084/1000RR 0.22 (0.08 to 0.6)95 (2 studies)ModerateOnly one of the two studies had blinded outcome assessment

Al-Kadri 2009

Estrogen with or without progesterone versus placebo
0/10000/1000OR 4.64 (0.25 to 87.71)172 (1 study)Very lowThere was no evidence of blinding , there was imprecision and the evidence was based on a single trial

Al-Kadri 2009

Estrogen with or without progesterone versus tibolone
91/1000400/1000OR 6.67 (0.6 to 74.51)21 (1 study)Very lowThere was no blinding and there was a lack of adequate detail on allocation concealment. Evidence was based on a single trial

 
Table 6. Fertility outcomes

Outcome

Intervention and comparison intervention
Illustrative comparative risks (95% CI)Relative effect

(95% CI)
Number of participants

(studies)
Quality of the evidence

(GRADE)
Comments






Assumed risk

with comparator
Corresponding risk

with intervention

Clinical pregnancy

Hughes 2007

Ovulation suppression versus placebo (for subfertile couples)
270/1000274/1000OR 1.02 (0.69 to 1.5)557 (11 studies)LowIncluded studies lacked adequate explanations for allocation concealment and blinding

Sallam 2006

Ultralong GnRHa agonist down-regulation versus no agonist
325/1000673/1000OR 4.28 (2.0 to 9,15)165 (3 studies)Very lowIncluded studies lacked blinding and explanations for allocation concealment. There was some imprecision

Hart 2008 Excisional versus ablative surgery for endometriomata170/1000518/1000OR 5.24 (1.92 to 14.27)88 (2 studies)LowIncluded studies lacked blinding and there was some imprecision

Flower 2012 Chinese herbal medicine versus gestrinone592/1000699/1000RR 1.18 (0.87 to 1.59)45 (1 study)LowEvidence based on a single study

Furness 2004

Post-surgical medical therapy versus pre and post-surgical medical therapy with GnRHa
500/10000/1000RR 0.0 (0 to 0)25 (1 study)Very lowIncluded studies lacked adequate explanation of randomisation, allocation concealment and there was no blinding

Furness 2004

Post-surgical medical therapy versus placebo/no treatment
246/1000207/1000RR 0.84 (0.59 to 1.18)420 (8 studies)LowIncluded studies lack ed adequate explanation of randomisation and blinding

Lu 2012 Laparoscopic surgery plus pentoxifylline versus laparoscopic surgery plus placebo196/1000273/1000OR 1.54 (0.89 to 2.66)285 (3 studies)Very lowLacked methodological detail, and lack of precision. No trial reported on live birth

Benschop 2010 Aspiration of endometrioma versus expectant management200/1000244/1000OR 1.29 (0.45 to 3.64)81 (1 study)LowThere was no blinding and evidence was based on a single trial

Benschop 2010 Cystectomy of endometrioma versus expectant management317/1000348/1000OR 1.15 (0.52 to 2.55)109 (1 study)LowThere was no blinding and evidence was based on a single trial

Benschop 2010 GnRH agonist versus GnRH antagonist for endometrioma242/1000206/1000OR 0.814 (0.26 to 2.54)67 (1 study)LowEvidence based on a single trial

Duffy 2014 Laparoscopic ablation or excision versus diagnostic laparoscopy186 per 1000302 per 1000 (223 to 396)OR 1.89 (1.25 to 2.86)528 (3 studies)ModerateTwo studies didnot adequately describe randomisation methods; one study was at high risk of attrition bias

Ongoing pregnancy (20 weeks) or live birth

Duffy 2014

Laparoscopic ablation or excision versus diagnostic laparoscopy
179 per 1000297 per 1000

(207 to 408)
OR 1.94 (1.20 to 3.16)382 (2 studies)ModerateOne study did not describe methods in detail, as it is only published as an abstract. Most of the data apply to ongoing pregnancy: of 92 events in this comparison, only 12 were live birth

Fetal loss or miscarriage

Duffy 2014

Laparoscopic surgery versus diagnostic laparoscopy
190/1000181/1000OR 0.94 (0.35 to 2.54)112 (2 studies)ModerateOne study did not describe methods in detail, as was only available as an abstract. The larger study (n=100 pregnancies) did not include fetal losses after 20 weeks

Benschop 2010 GnRH agonist versus GnRH antagonist for endometrioma prior to ART30/100029/1000OR 0.97 (0.06 to 15.85)67 (1 study)LowEvidence based on a single trial and wide confidence intervals are indicative of some imprecision

Benschop 2010 Aspiration of endometrioma versus expectant management100/100097/1000OR 0.97 (0.23 to 4.15)81 (1 study)LowThere was no blinding and the evidence is based on a single trial