Materials and Methods
Sources
A protocol with explicitly defined objectives, criteria for study selection, and approaches assessing outcome selection was developed. The systematic review was registered with the Core Outcome Measures in Effectiveness Trials Initiative Register and conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.
A comprehensive and systematic literature review was undertaken searching the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and Medline from database inception to November 2014 (see Appendix ). We searched the Cochrane Register of Systematic reviews to identify relevant Cochrane systematic reviews searching the bibliography for eligible trials.
Study selection
Two reviewers (M.H. and J.M.D.) independently screened titles and abstracts. They critically reviewed the full text of selected studies to assess eligibility. Any discrepancies between the reviewers were resolved by discussion with a third author (K.S.K.). We included randomized control trials assessing the effectiveness of any surgical intervention with or without an adjuvant medical therapy for the treatment of pain and subfertility associated with endometriosis. We excluded quasirandomized, nonrandomized, analytical, and diagnostic studies.
Two reviewers (M.H. and J.D.) extracted the data independently using a piloted data extraction sheet. The study characteristics were extracted from the trial report including the publishing journal, study design, setting, participants, interventions, sample size calculation, and the pharmaceutical funding. The impact factor in the year of publication was identified by reviewing data provided by Researchgate. We systematically reviewed primary and secondary outcomes and their definitions and instruments. The study characteristics and outcomes were summarized in tabular form and presented with descriptive statistics within summary tables and diagrams ( Table 1 ).
| Study | IF | Method quality | Outcome quality | Intervention group 1 | Intervention group 2 | Intervention group 3 |
|---|---|---|---|---|---|---|
| Abbott et al, 2004 | 3.17 | 5 | 4 | Diagnostic laparoscopy plus delayed surgical treatment | Surgical treatment plus repeat surgery | |
| Abu Hashim et al, 2012 | 1.85 | 5 | 6 | Surgical treatment plus superovulation with letrozole plus intrauterine insemination | Surgical treatment plus superovulation with clomiphene citrate plus intrauterine insemination | |
| Acién et al, 2002 | 3.202 | 2 | 2 | Surgical treatment plus interferon α-2b | Surgical treatment plus saline | |
| Alborzi et al, 2004 | 3.17 | 2 | 5 | Surgical treatment plus ovarian fenestration and coagulation | Surgical treatment plus ovarian cystectomy | |
| Alborzi et al, 2007 | 3.168 | 2 | 2 | Surgical treatment plus ovarian fenestration and coagulation | Surgical treatment plus ovarian cystectomy | Surgical treatment plus ovarian fenestration and cystectomy |
| Alborzi et al, 2011 | 1.072 | 2 | 2 | Surgical treatment plus GnRHa | Surgical treatment plus aromatase inhibitor | Surgical treatment |
| Alkatout et al, 2013 | 1.575 | 2 | 2 | Surgical treatment | HT | Surgical treatment plus hormone therapy |
| Audebert et al, 1998 | 0.745 | 2 | 2 | Surgery treatment plus GnRHa | GnRHa plus surgical treatment | |
| Ballester et al, 2011 | 3.468 | 2 | 4 | Laparoscopy plus colorectal resection | Laparotomy plus colorectal resection | |
| Beretta et al, 1998 | 3.344 | 2 | 2 | Surgical treatment plus ovarian cystectomy | Surgical treatment plus ovarian fenestration and coagulation | |
| Bianchi et al, 1999 | 3.643 | 3 | 2 | Surgical treatment plus danocrine | Surgical treatment | |
| Busacca et al, 2001 | 2.751 | 3 | 2 | Surgical treatment plus GnRH agonist | Surgical treatment | |
| Candiani et al, 1992 | 1.982 | 3 | 3 | Surgical treatment plus presacral neurectomy | Surgical treatment | |
| Cobellis et al, 2011 | 1.974 | 5 | 3 | Surgery treatment plus fatty acid amide | Surgical treatment plus selective COX2 NSAID | Surgical treatment |
| Cosson et al, 2002 | 3.202 | 3 | 4 | Surgical treatment plus progestin | Surgical treatment plus GnRHa | |
| Costello et al, 2010 | 3.122 | 5 | 6 | Surgical treatment plus multimodal intraoperative analgesia | Surgical treatment plus placebo | |
| Creus et al, 2008 | 2.537 | 5 | 0 | Surgical treatment plus xanthine derivative | Surgical treatment plus placebo | |
| Darai et al, 2010 | 7.474 | 3 | 5 | Laparoscopy plus colorectal resection | Laparotomy plus colorectal resection | |
| Darai et al, 2011 | 3.564 | 3 | 2 | Laparoscopy plus colorectal resection | Laparotomy plus colorectal resection | |
| diZerega et al, 2007 | 3.168 | 5 | 3 | Surgical treatment plus adhesion barrier gel | Surgical treatment | |
| Healey et al, 2010 | 3.122 | 5 | 3 | Surgical treatment plus ablation | Surgical treatment plus excision | |
| Hoo et al, 2014 | 3.483 | 5 | 6 | Surgical treatment plus ovarian suspension | Surgical treatment | |
| Jarrell et al, 2005 | – | 5 | 2 | Surgical treatment | Diagnostic laparoscopy plus biopsy | |
| Kamencic et al, 2008 | – | 3 | 2 | Surgical treatment plus xanthine derivative | Surgical treatment | |
| Koninckx et al, 2013 | 2.03 | 5 | 6 | Surgical treatment plus humidified CO 2 pneumoperitoneum | Surgical treatment plus peritoneal full conditioning and barrier gel | |
| Lalchandani et al, 2005 | – | 2 | 3 | Diagnostic laparoscopy plus GnRHa plus HT | Surgical treatment plus helium thermal coagulator | |
| Loverro et al, 2008 | 1.565 | 5 | 2 | Surgical treatment plus GnRHa | Surgical treatment plus placebo | |
| Mais et al, 1995 | – | 2 | 5 | Surgical treatment plus adhesion barrier | Surgical treatment | |
| Marcoux et al, 1997 | 27.766 | 5 | 6 | Surgical treatment plus ablation | Surgical treatment plus excision | |
| Matorras et al, 2002 | 3.202 | 2 | 2 | Bilateral salpingo-oophrectomy plus HT | Bilateral salpingo-oophrectomy | |
| Moini et al, 2012 | 0.471 | 5 | 4 | Surgical treatment | Diagnostic Laparoscopy | |
| Morgante et al, 1999 | 3.643 | 2 | 3 | Surgical treatment plus GnRHa plus danocrine | Surgical treatment plus GnRHa | |
| Nowroozi et al, 1987 | – | 3 | 1 | Surgical treatment plus ablation | Diagnostic laparoscopy | |
| Parazzini et al, 1994 | 2.247 | 5 | 3 | Surgical treatment plus GnRHa | Surgical treatment | |
| Parazzini et al, 1999 | 3.643 | 3 | 2 | Surgical treatment plus ablation | Surgical treatment plus excision | Diagnostic laparoscopy |
| Seiler et al, 1986 | – | 3 | 0 | Surgical treatment plus ablation | Treatment with danocrine | |
| Soysal et al, 2004 | 3.072 | 5 | 4 | Surgical treatment plus GnRHa | Surgical treatment plus GnRHa plus aromatase inhibitor | |
| Surrey et al, 1994 | – | 2 | 3 | GIFT plus surgical treatment | GIFT | |
| Sutton et al, 1994 | 2.464 | 5 | 3 | Surgical treatment plus presacral neurectomy | Diagnostic laparoscopy | |
| Sutton et al, 1997 | 2.612 | 4 | 2 | Surgical treatment plus presacral neurectomy | Diagnostic laparoscopy | |
| Sutton et al, 2001 | 0.63 | 5 | 2 | Surgical treatment plus presacral neurectomy | Surgical treatment | |
| Tanmahasamut et al, 2012 | 4.798 | 5 | 5 | Surgical treatment plus Mirena IUS | Surgical treatment | |
| Telimaa et al, 1988 | – | 4 | 1 | Surgical treatment plus danocrine | Surgical treatment plus progestin | Surgical treatment plus placebo |
| Tsai et al, 2004 | 0.778 | 5 | 2 | Surgical treatment plus GnRHa | Surgical treatment plus danocrine | Surgical treatment |
| Vercellini et al, 1999 | 2.657 | 3 | 4 | Surgical treatment plus GnRHa | Surgical treatment | |
| Vercellini et al, 2002 | 3.202 | 3 | 4 | Surgical treatment plus progestin | Surgical treatment plus COCP | |
| Vercellini et al, 2003 | 3.483 | 5 | 5 | Surgical treatment plus presacral neurectomy | Surgical treatment | |
| Vercellini et al, 2003 | 3.483 | 3 | 3 | Surgical treatment plus Mirena IUS | Surgical treatment | |
| Wickström et al, 2012 | 4.542 | 5 | 3 | Tubal pertubation plus lidocaine | Tubal pertubation plus placebo | |
| Wright et al, 2005 | 3.114 | 4 | 2 | Surgical treatment plus ablation | Surgical treatment plus excision | |
| Zhao et al, 2013 | 1.401 | 1 | 2 | Surgical treatment plus Chinese medicine | Surgical treatment plus GnRHa plus HT | Surgical treatment plus progestin |
| Zhao et al, 2013 | 1.401 | 3 | 6 | Surgical treatment plus Chinese medicine | Surgical treatment plus GnRHa plus HT | Surgical treatment plus progestin |
| Zhu et al, 2014 | 1.877 | 3 | 2 | Surgical treatment plus COCP | Surgical treatment plus COCP plus Chinese medicine | Surgical treatment |
| Zullo et al, 2003 | 2.518 | 5 | 4 | Surgical treatment plus presacral neurectomy | Surgical treatment |
Quality assessment
Two reviewers (M.H. and J.D.) independently assessed each study’s methodological quality using the JADAD criteria. The 5 point validated scoring system assesses the following: (1) was the trial described as randomized (1 point); (2) did the trial use an appropriate method of randomization (1 point); (3) was the trial blinded (1 point); (4) did the trial use an appropriate method of blinding? (1 point); and (5) did the trial account for all patients randomized (1 point)?
Two reviewers (M.H. and J.D.) independently assessed each study’s outcome reporting using the 6 point Management of Otitis Media with Effusion in Cleft Palate scoring system validated for the development of a core outcome set : (1) was a primary outcome stated (1 point); (2) was the primary outcome clearly defined for reproducible measures (1 point); (3) were the secondary outcomes clearly stated (1 point); (4) were the secondary outcomes clearly defined for reproducible measures (1 point); (5) do the authors explain the choice of outcome (1 point); and (6) are the methods used designed to enhance quality of measures appropriate (1 point)? There is no defined rating score; therefore, a previously used cutoff value of ≥ 4 was used to represent high-quality trials.
Analysis
Univariate association between continuous factors was assessed by nonparametric correlation coefficient (Spearman rho). The comparison of outcome reporting quality was assessed between groups according to type of journal (general vs specialist), funding source (commercial or other), year of publication, and impact factor in the year of publication. Journals specific to obstetrics and gynecology as listed by www.scimagojr.com were classified as specialist. Funding status was identified in the article text including commercial funding or the donation of equipment, which had facilitated the trial. These univariate analyses were performed using nonparametric Mann Whitney U tests.
To assess the multivariate relationship with quality of outcome reporting, we used a multivariate linear regression model including journal type, impact factor in the year of publication, year of publication, and methodological quality as independent variables and outcome reporting as the dependent variable. Only significant predictors were retained in the final model. We globally checked linear regression assumptions by exploring residuals vs predicted plot. All the analyses were performed using Stata program (StataCorp, 2013, Stata Statistical Software, release 13; StataCorp LP, College Station, TX).
Results
The search strategy identified 1570 titles and abstracts. We screened 1409 titles and abstracts following the exclusion of 161 duplicate records ( Figure 1 ). We included 54 RCTs ( Table 1 ). The included trials collected and reported 164 outcomes and 113 outcome measures ( Table 2 ). Unfortunately, the outcome measurement or definition was not described within the trial report for 110 outcomes.
| Domain | RCTs | Outcomes | Outcome measure |
|---|---|---|---|
| Pain | 37 | 32 | 24 |
| Subfertility | 32 | 28 | 11 |
| Quality of life | 9 | 10 | 10 |
| Surgical adverse events | 14 | 34 | 5 |
| Medical adverse events | 8 | 22 | 0 |
The most common outcome domains were pain (29 of 54 trials [53%]), subfertility (22 of 54 trials [41%]), and quality of life (9 of 54 trials [17%]). When considering the pain domain, commonly reported pain outcomes were dysmenorrhea (23 RCTs, 10 outcome measures), dyspareunia (21 RCTs, 11 outcome measures), and pelvic pain (15 RCTs, 9 outcome measures). Three trials did not specify the outcome measure used to assess pain ( Tables 2–4 ).
| Outcome domain | Outcome | Trials, n |
|---|---|---|
| Fertility outcomes | Pregnancy | 26 |
| Miscarriage | 7 | |
| Live birth | 5 | |
| Estradiol | 5 | |
| Ectopic pregnancy | 4 | |
| Endometrial thickness | 2 | |
| Number of follicles > 18 mm | 3 | |
| Ampules of gonadotropin | 1 | |
| Days of stimulation | 1 | |
| Early fetal loss | 1 | |
| Embryos per cycle | 1 | |
| Follicular-stimulating hormone | 1 | |
| Luteinizing hormone | 1 | |
| Number of oocytes per cycle | 1 | |
| Pregnancy interval | 1 | |
| Pregnancy subsequent cycle | 1 | |
| Reproductive outcome | 1 | |
| Singleton delivery | 1 | |
| Stillbirth | 1 | |
| Term delivery | 2 | |
| Twin delivery | 1 | |
| Twin pregnancy | 1 | |
| Vaginal delivery | 1 | |
| Pain outcomes | Dysmenorrhea | 23 |
| Dyspareunia | 21 | |
| Pelvic pain | 15 | |
| Nonmenstrual pelvic pain | 6 | |
| Dyschezia | 6 | |
| Overall pain | 5 | |
| Postoperative pain | 3 | |
| Abdominal pain | 2 | |
| Back pain | 2 | |
| Aggregate pain | 1 | |
| Analgesia use | 3 | |
| Analgesic requirement | 2 | |
| Chest discomfort | 1 | |
| General discomfort | 1 | |
| General pain | 1 | |
| Global intensity of pain | 1 | |
| Lateral menstrual pain | 1 | |
| Painless first stage of labor | 1 | |
| Postoperative opioid analgesia | 1 | |
| Rectal pain | 1 | |
| Shoulder pain | 1 | |
| Thigh pain | 1 | |
| Voiding pain | 1 |
| Outcome | Outcome measure | n |
|---|---|---|
| Dysmenorrhea | Visual analog scale (0–10) | 8 |
| Visual analog scale (0–100) | 7 | |
| Visual analog scale (0–10 with description) | 3 | |
| Visual analog scale (no description) | 1 | |
| Ranked ordinal scale (1–5) | 1 | |
| Likert scale (0–10) | 3 | |
| Questionnaire (with description) | 2 | |
| Questionnaire (ranked symptoms) | 1 | |
| Questionnaire (no description) | 1 | |
| Number of episodes | 1 | |
| Not specified | 2 | |
| Pregnancy | Serum βHCG | 4 |
| Ultrasound (visualizing fetal heart) | 4 | |
| Ultrasound (growth scan) | 2 | |
| Not specified | 20 | |
| Quality of life | World Health Organization Quality of Life-BREF | 1 |
| EuroQol-5D | 1 | |
| Short-Form Health Survey 12 | 1 | |
| Short-Form Health Survey 36 | 6 | |
| Hospital Anxiety and Depression Scale | 2 | |
| Greene Climateric Scale | 1 | |
| Blatt Kupperman Menopausal Index | 1 | |
| Sabbatsberg Sexual Rating Scale | 1 | |
| Revised Sabbatsberg Sexual Rating Scale | 2 | |
| Sexual Activity Questionnaire | 1 |
Dysmenorrhea was measured by 10 different outcome measures: a visual analog scale anchored between 0 and 10; a visual analog scale anchored between 0 and 100; a visual analog scale anchored between 0 (no pain) and 10 (severe pain); a visual analog scale with no specified parameters; a questionnaire including 3 domains of activities of daily living, coexistence of systemic symptoms, and analgesic requirement; a questionnaire with ranked symptoms; a questionnaire with no further description available; a ranked ordinal scale (1–5); number of episodes; and not specified.
The 3 most commonly reported fertility outcomes were pregnancy (26 RCTs, 5 outcome measures), miscarriage (7 RCTs, 2 outcome measures), and live birth (5 RCTs, 2 outcome measures). Pregnancy was measured with the following outcome measures: ultrasound scan visualizing fetal heart; ultrasound growth scan; serum beta HCG; pregnancy greater than 20 weeks’ gestation; not specified ( Tables 3 and 4 and Figure 2 ).
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