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The Cochrane Database of Systematic Reviews logoLink to The Cochrane Database of Systematic Reviews
. 2020 Oct 23;2020(10):CD011031. doi: 10.1002/14651858.CD011031.pub3

Laparoscopic surgery for endometriosis

Celine Bafort 1, Yusuf Beebeejaun 2, Carla Tomassetti 1, Jan Bosteels 3, James MN Duffy 4,5,
Editor: Cochrane Gynaecology and Fertility Group
PMCID: PMC8428328  PMID: 33095458

Abstract

Background

Endometriosis is associated with pain and infertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy.

Objectives

To assess the effectiveness and safety of laparoscopic surgery in the treatment of pain and infertility associated with endometriosis.

Search methods

This review has drawn on the search strategy developed by the Cochrane Gynaecology and Fertility Group including searching the Cochrane Gynaecology and Fertility Group's specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, reference lists for relevant trials, and trial registries from inception to April 2020.

Selection criteria

We selected randomised controlled trials (RCTs) that compared the effectiveness and safety of laparoscopic surgery with any other laparoscopic or robotic intervention, holistic or medical treatment, or diagnostic laparoscopy only.

Data collection and analysis

Two review authors independently performed selection of studies, assessment of trial quality and extraction of relevant data with disagreements resolved by a third review author. We collected data for the core outcome set for endometriosis. Primary outcomes included overall pain and live birth. We evaluated the quality of evidence using GRADE methods.

Main results

We included 14 RCTs. The studies randomised 1563 women with endometriosis. Four RCTs compared laparoscopic ablation or excision with diagnostic laparoscopy only. Two RCTs compared laparoscopic excision with diagnostic laparoscopy only. One RCT compared laparoscopic ablation or excision with laparoscopic ablation or excision and uterine suspension. Two RCTs compared laparoscopic ablation and uterine nerve transection with diagnostic laparoscopy only. One RCT compared laparoscopic ablation with diagnostic laparoscopy and gonadotropin‐releasing hormone (GnRH) analogues. Two RCTs compared laparoscopic ablation with laparoscopic excision. One RCT compared laparoscopic ablation or excision with helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy. One RCT compared conservative laparoscopic surgery with laparoscopic colorectal resection of deep endometriosis infiltrating the rectum. Common limitations in the primary studies included lack of clearly described blinding, failure to fully describe methods of randomisation and allocation concealment, and poor reporting of outcome data.

Laparoscopic treatment versus diagnostic laparoscopy

We are uncertain of the effect of laparoscopic treatment on overall pain scores compared to diagnostic laparoscopy only at six months (mean difference (MD) 0.90, 95% confidence interval (CI) 0.31 to 1.49; 1 RCT, 16 participants; very low quality evidence) and at 12 months (MD 1.65, 95% CI 1.11 to 2.19; 1 RCT, 16 participants; very low quality evidence), where a positive value means pain relief (the higher the score, the more pain relief) and a negative value reflects pain increase (the lower the score, the worse the increase in pain). No studies looked at live birth.

We are uncertain of the effect of laparoscopic treatment on quality of life compared to diagnostic laparoscopy only: EuroQol‐5D index summary at six months (MD 0.03, 95% CI –0.12 to 0.18; 1 RCT, 39 participants; low quality evidence), 12‐item Short Form (SF‐12) mental health component (MD 2.30, 95% CI –4.50 to 9.10; 1 RCT, 39 participants; low quality evidence) and SF‐12 physical health component (MD 2.70, 95% CI –2.90 to 8.30; 1 RCT, 39 participants; low quality evidence). Laparoscopic treatment probably improves viable intrauterine pregnancy rate compared to diagnostic laparoscopy only (odds ratio (OR) 1.89, 95% CI 1.25 to 2.86; 3 RCTs, 528 participants; I2 = 0%; moderate quality evidence). We are uncertain of the effect of laparoscopic treatment compared to diagnostic laparoscopy only on ectopic pregnancy (MD 1.18, 95% CI 0.10 to 13.48; 1 RCT, 100 participants; low quality evidence) and miscarriage (MD 0.94, 95% CI 0.35 to 2.54; 2 RCTs, 112 participants; low quality evidence). There was limited reporting of adverse events. No conversions to laparotomy were reported in both groups (1 RCT, 341 participants).

Laparoscopic ablation and uterine nerve transection versus diagnostic laparoscopy

We are uncertain of the effect of laparoscopic ablation and uterine nerve transection on adverse events (more specifically vascular injury) compared to diagnostic laparoscopy only (OR 0.33, 95% CI 0.01 to 8.32; 1 RCT, 141 participants; low quality evidence). No studies looked at overall pain scores (at six and 12 months), live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage.

Laparoscopic ablation versus laparoscopic excision

There was insufficient evidence to determine whether there was a difference in overall pain, measured at 12 months, for laparoscopic ablation compared with laparoscopic excision (MD 0.00, 95% CI –1.22 to 1.22; 1 RCT, 103 participants; very low quality evidence). No studies looked at overall pain scores at six months, live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy, miscarriage and adverse events.

Helium thermal coagulator versus electrodiathermy

We are uncertain whether helium thermal coagulator compared to electrodiathermy improves quality of life using the 30‐item Endometriosis Health Profile (EHP‐30) at nine months, when considering the components: pain (MD 6.68, 95% CI –3.07 to 16.43; 1 RCT, 119 participants; very low quality evidence), control and powerlessness (MD 4.79, 95% CI –6.92 to 16.50; 1 RCT, 119 participants; very low quality evidence), emotional well‐being (MD 6.17, 95% CI –3.95 to 16.29; 1 RCT, 119 participants; very low quality evidence) and social support (MD 5.62, 95% CI –6.21 to 17.45; 1 RCT, 119 participants; very low quality evidence). Adverse events were not estimable. No studies looked at overall pain scores (at six and 12 months), live birth, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy and miscarriage.

Authors' conclusions

Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. No data were reported on live birth. There is moderate quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound compared to diagnostic laparoscopy only. No studies were found that looked at live birth for any of the comparisons. Further research is needed considering the management of different subtypes of endometriosis and comparing laparoscopic interventions with lifestyle and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

Plain language summary

Laparoscopic surgery for pain and infertility associated with endometriosis

Background

Endometriosis is the presence of tissue that normally lines the uterus (womb) in sites other than the uterine cavity, such as the ovaries (where eggs are produced), fallopian tubes (which link the ovaries and uterus) and the pelvis. It can cause pain, infertility, and other symptoms which can reduce quality of life. Different treatments for endometriosis are available, one of which is laparoscopic ('keyhole') surgery, performed to remove visible areas of endometriosis. Cochrane Review authors assessed the evidence on the use of laparoscopic surgery to treat pain and fertility problems in women with endometriosis. Laparoscopic surgical techniques include ablation, which means destruction of a lesion (for example, by burning), and excision, which means cutting a lesion out.

Study characteristics

We included 14 clinical trials (involving 1563 participants). They were conducted in Australia, Canada, Egypt, France, Italy, Iran and the UK. Most compared laparoscopic ablation or excision versus diagnostic laparoscopy. Only six of the 14 included trials reported their source of funding. The evidence was current to April 2020.

Key results

We found that it is uncertain whether laparoscopic surgery improves overall pain compared to diagnostic laparoscopy only. Unfortunately, there were no data on live birth; however, we found that laparoscopic surgery may increase intrauterine (within the womb) pregnancy rates compared to diagnostic laparoscopy only. We are uncertain whether laparoscopic excision is more effective than ablation in relieving pain, although this result came from a single study. There was insufficient evidence on side effects to allow any conclusions to be drawn regarding safety.

Quality of the evidence

The quality of the evidence was moderate to very low with regard to the effectiveness of laparoscopic surgery. Additional studies are needed in this field, and these should report certain specific endpoints for endometriosis (i.e. the core outcome set, developed by healthcare professionals, researchers and women with endometriosis) and adverse events as an outcome.

Summary of findings

Background

Description of the condition

Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity, such as the ovaries, fallopian tubes and the pelvis. Despite extensive basic and clinical research, the exact pathogenesis of the disease remains controversial. Possible mechanisms include induction, in situ development and transplantation (Burney 2012). Transplantation describes the process of endometrial cells transported along the fallopian tubes (retrograde menstruation) and through blood‐borne or lymphatic spread from the uterus to another location inside the body. The induction theory hypothesises that combinations of hormonal, immunological and genetic factors combine to induce endometrial differentiation in undifferentiated cells (Merrill 1966). In situ development hypothesises the development of endometriosis from embryological remnants of structures which contribute to the uterine cavity (Russell 1979).

Endometriosis is a common condition. The prevalence (frequency of diagnosis among women in a given period of time) is between 3% and 6% in women aged 15 to 44 years (Eskenazi 1997; Giudice 2012; Houston 1988; Mahmood 1991; Missmer 2003; Strathy 1982; Vigano 2004). Differences in the reported prevalence of endometriosis may reflect the different inclusion criteria for each study, the indications for surgery and the attention paid by surgeons in identifying endometriosis. No studies have been conducted on representative samples of the general population.

Endometriosis can be suspected based on a careful history and physical examination performed by an experienced gynaecologist. Unfortunately, peritoneal endometriosis cannot be identified by any imaging modality. Ovarian endometriosis or endometriotic cysts can easily be visualised by transvaginal ultrasound. Transvaginal or endoanal ultrasound can also diagnose the presence of deep infiltrating endometriosis in the anterior compartment (i.e. bladder and its specific location) or posterior compartment (i.e. rectovaginal septum, uterosacral ligaments, torus uterinus, vaginal fornix and bowel involvement) when performed by an experienced operator (Guerriero 2016). The gold standard test is to diagnose endometriosis with direct biopsy at laparoscopy establishing a histological diagnosis. The revised American Society for Reproductive Medicine classification (rASRM) provides a numerical score of severity based on visual findings at laparoscopy (ASRM 1997). Unfortunately the value of all staging systems including rASRM is limited by the diversity of the disease and the wide variations in reported symptoms (Kurata 1993; Vercellini 1996).

Pain is recognised as the primary complaint of women with endometriosis. Endometriosis is a variable condition exemplified by the nature and severity of pain symptoms experienced (Giudice 2004). Women can experience a wide range of pain including dysmenorrhoea (pain with menstruation), pelvic pain (pain not related to menstruation) and dyspareunia (pain with intercourse) (Hirsch 2016). Women with endometriosis may present with pain related to the gastrointestinal tract and bladder, pain referred to distant sites as well as nerve entrapment and neuropathic pain. This variability reflects the diverse mechanisms responsible for the sensation of pain. Relatively little is known about the mechanisms which trigger the sensations of pain in endometriosis (Morotti 2016). Endometriosis lesions contain high numbers of sensory and autonomic nerve fibres which provide a route for painful stimuli. Endometriosis has features of an inflammatory process that stimulates a wide range of immune and inflammatory cells. These immune cells secrete immune modulators, which can stimulate the sensation of pain. Pain and other symptoms can have a substantial impact on quality of life.

Infertility is associated with endometriosis, with studies reporting 30% to 50% of women with endometriosis being subfertile (Practice Committee ASRM 2012). A cause and effect relationship between endometriosis and infertility has not been established (Giudice 2012). Severe endometriosis adversely affects fertility by virtue of the distortion or obliteration of functional anatomy alone. However, the role of minimal to moderate endometriosis in infertility remains controversial. It has been hypothesised that a combination of deregulation of biomarkers responsible for endometrial receptivity including endometrial progesterone resistance, increased cell proliferation and decreased cell apoptosis results in infertility (Giudice 2012). With no intervention, 50% of women with mild endometriosis will conceive, only 25% with moderate endometriosis will conceive and only a few with severe disease will conceive (Practice Committee ASRM 2012).

Description of the intervention

Conservative, holistic and medical interventions exist for the management of endometriosis. Several Cochrane Reviews have evaluated holistic interventions including acupuncture (Zhu 2011), medical interventions including analgesics (Brown 2017), Chinese herbal medicines (Flower 2012), modulators of the inflammatory and immune systems (Lu 2012; Lu 2013), ovarian suppression (Brown 2010; Brown 2012; Brown 2018), intrauterine devices (Abou‐Setta 2013), and surgical interventions with medical interventions which act as adjuvants to surgery (Yap 2004). Unfortunately, hormonal medical interventions provide contraception and, therefore, are not appropriate for women seeking treatment for infertility. A review that summarises all Cochrane Reviews concerning all interventions for endometriosis has been published (Brown 2014).

Surgical interventions may be performed robotically, laparoscopically (keyhole) or as an open (laparotomy) procedure. Within high resource settings, a laparoscopic approach is now considered routine for the diagnosis and removal of endometriosis as it offers several advantages when compared to open procedures including decreased recovery time and cost (Ahmad 2019; Somigliana 2009). Laparoscopic surgery aims to destroy or remove all visible endometriotic lesions and repair the damage to organs and other sites caused by endometriosis, which restores the normal anatomy. Laparoscopic excision of peritoneal deposits of endometriosis may be accomplished utilising different techniques including sharp dissection, electro‐excision, Argon Neutral Plasma Energy, laser energy, ultrasound scalpel or helium thermal coagulator. Electrocautery or Argon Neutral Plasma Energy may be utilised to ablate peritoneal deposits of endometriosis. With appropriate expertise and setting, a laparoscopic approach can manage moderate to severe endometriosis. Severe endometriosis involving the bowel, rectum and bladder may require a multidisciplinary team involving gynaecologists, general surgeons and urologists, requiring significant expertise. The removal of moderate to severe endometriosis may result in significant complications caused by damaging important organs and structures. In addition, the destruction of the nerve pathways thought to be responsible for carrying pain fibres (uterine nerve ablation and presacral neurectomy) aims to reduce pain associated with endometriosis. The role of laparoscopic surgery for the treatment of infertility associated with endometriosis remains controversial (Vercellini 2009). It is debated whether artificial reproductive technology (e.g. in vitro fertilisation (IVF)) should be considered instead of surgery to achieve conception (Vercellini 2020).

How the intervention might work

Laparoscopic surgery aims to treat the structural causes of pain, infertility and other symptoms associated with endometriosis by restoring the normal anatomy by destroying or removing all visible endometriotic lesions, performing adhesiolysis, and repairing damaged organs and other sites (Berlanda 2013). Eliminating endometriotic lesions and restoring normal anatomy may not reverse the inflammatory and biomolecular changes which result in persisting pain, or the deregulation of biomarkers of endometrial receptivity which contributes to infertility including endometrial progesterone resistance, increased cell proliferation and decreased cell apoptosis.

Why it is important to do this review

This review assesses and summarises the current evidence comparing laparoscopic surgical intervention methods with other treatment modalities, as well as comparing the efficacy of different laparoscopic techniques in the treatment of pelvic pain and infertility associated with endometriosis. One systematic review evaluated the quality of online information concerning endometriosis and identified examples of outdated, inaccurate or even dangerous information (Hirsch 2017). With such a wide variety of different conservative, medical and surgical interventions available, the comparisons within the review should assist women with endometriosis and their clinicians in choosing management plans with a better knowledge of the current evidence. There is substantial variation in the recommendations of current clinical practice guidelines for endometriosis (Hirsch 2018). It is anticipated the review will inform the development of future endometriosis guidelines. The review serves to highlight the current limitations in the literature and to highlight the need for further research.

Objectives

To assess the effectiveness and safety of laparoscopic surgery in the treatment of pain and infertility associated with endometriosis.

Methods

Criteria for considering studies for this review

Types of studies

Published and unpublished randomised controlled trials (RCTs) were eligible for inclusion. We excluded non‐randomised and quasi‐randomised trials as they are associated with a high risk of bias.

Types of participants

Women with minimal to severe endometriosis confirmed with a visual diagnosis at diagnostic or operative laparoscopy.

Types of interventions

We included trials if they compared any laparoscopic intervention with another laparoscopic or robotic intervention, holistic or medical intervention, or diagnostic laparoscopy.

Specific laparoscopic or robotic procedures of the surgical interventions assessed included:

  1. excision of peritoneal deposits utilising any technique including sharp dissection, electro‐excision, Argon Neutral Plasma Energy, laser energy, ultrasound scalpel or helium thermal coagulator;

  2. ablation of peritoneal deposits utilising any technique including electrocautery, Argon Neutral Plasma Energy, laser energy, ultrasound scalpel or helium thermal coagulator;

  3. treatment of moderate and severe endometriosis utilising any technique including shaving, disc excision (using transanal staplers, i.e. semicircular staplers or end to end circular staplers) or segmental colorectal resection.

Types of outcome measures

A minimum data set, known as a core outcome set, has been developed using formal consensus methods involving 116 healthcare professionals, 32 researchers and 206 women with endometriosis from 29 countries (Duffy 2020a). Over 80 speciality journals, including the Cochrane Gynaecology and Fertility Group (CGFG), have committed to supporting the implementation of the core outcome set for endometriosis (Duffy 2017a). Consensus definitions have been developed for fertility outcomes and will be implemented in this review (Duffy 2020b). Standardised measurement instruments for pain and other symptoms are currently in development and will be included in the next update of the review.

Primary outcomes

The primary outcome depended upon the primary symptom being treated.

  1. Overall pain measured by a continuous measure, for example, visual analogue scale (VAS).

  2. Live birth defined as the complete expulsion or extraction from a woman of a product of fertilisation, after 20 completed weeks of gestational age; which, after such separation, breathed or showed any other evidence of life, such as heart beat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord had been cut or the placenta was attached. A birth weight of 350 g or more was used if gestational age was unknown (accounting for singleton, twin and higher multiple pregnancies).

Secondary outcomes

The secondary outcomes depended upon the primary symptom being treated.

  1. Improvement in the most troublesome symptom.

  2. Quality of life.

  3. Viable intrauterine pregnancy confirmed by ultrasound defined as a pregnancy diagnosed by ultrasonographic examination of at least one fetus with a discernible heartbeat.

  4. Pregnancy loss accounting for:

    1. ectopic pregnancy defined as a pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualisation or histopathology;

    2. miscarriage defined as the spontaneous loss of an intrauterine pregnancy prior to 20 completed weeks of gestational age;

    3. stillbirth defined as the death of a fetus prior to the complete expulsion or extraction from its mother after 20 completed weeks of gestational age (SCRN 2003). Death was determined by the fact that, after such separation, the fetus did not breathe or show any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles;

    4. termination of pregnancy defined as the intentional loss of an intrauterine pregnancy, through intervention by medical, surgical or unspecified means.

  5. Gestational age at birth defined as the age of a fetus calculated by the best obstetric estimate determined by assessments which may have included early ultrasound, and the date of the last menstrual period, or perinatal details, or both. In the case of assisted reproductive techniques, it was calculated by adding 14 days to the number of completed weeks since fertilisation.

  6. Birth weight collected within 24 hours of birth and assessed using a calibrated electronic scale with 10 g resolution.

  7. Neonatal mortality defined as death of a live born baby within 28 days of birth. This could be subdivided into early neonatal mortality, if death occurred in the first seven days after birth and late neonatal mortality, if death occurred between eight and 28 days after birth.

  8. Major congenital anomaly defined as a structural, functional and genetic anomalies that occur during pregnancy, and identified antenatally, at birth or later in life, and required surgical repair of a defect, or were visually evident, or were life‐threatening, or caused death.

  9. Adverse events including:

    1. mortality;

    2. vascular injury (major and abdominal wall vessels);

    3. visceral injury (bladder including ureters or bowel injury);

    4. solid organ injury (uterus);

    5. conversion to laparotomy;

    6. infection (intra‐abdominal, urinary, wound);

    7. venous thromboembolism.

  10. Participant satisfaction with treatment.

Search methods for identification of studies

We searched for all published and unpublished RCTs, without language restriction and in consultation with the CGFG Information Specialist (Marian Showell).

Electronic searches

We searched the following electronic databases, trial registers and websites (from inception to April 2020).

  1. CGFG Specialised Register of controlled trials; ProCite platform, searched 20 April 2020 (Appendix 1).

  2. CENTRAL via the Cochrane Register of Studies Online (CRSO); web platform, searched 20 April 2020 (Appendix 2).

  3. MEDLINE; Ovid platform, searched from 1946 to 20 April 2020 (Appendix 3).

  4. Embase; Ovid platform, searched from 1980 to 20 April 2020 (Appendix 4).

  5. PsycINFO; Ovid platform, searched from 1806 to 20 April 2020 (Appendix 5).

  6. CINAHL; Ebsco platform, searched from 1961 to 20 April 2020 (Appendix 6).

Other electronic searches we performed included the following.

  1. Trial registers for ongoing and registered trials: clinicaltrials.gov and www.who.int/trialsearch/Default.aspx; web platform, searched 20 April 2020 (Appendix 7).

  2. Citation indexes: scientific.thomson.com/products/sci.

  3. Conference abstracts in the Web of Knowledge: wokinfo.com.

  4. LILACS database: lilacs.bvsalud.org/en/.

  5. PubMed: www.ncbi.nlm.nih.gov/pubmed/.

  6. OpenGrey database: opengrey.eu/ and Google for grey literature.

Searching other resources

We handsearched reference lists of articles retrieved by the search and contacted experts in the field to obtain additional data. In addition, we handsearched relevant journals and conference abstracts that are not covered in the CGFG register, in liaison with the Information Specialist.

We did not perform a separate search for adverse effects of laparoscopic surgery for endometriosis. We considered adverse effects described in the studies only.

Data collection and analysis

Selection of studies

We used Covidence (Covidence) for screening and study selection. Two review authors (CB and YB) independently screened the titles and abstracts retrieved by the search. We then retrieved the full texts of all potentially eligible studies. Two review authors (CB and YB) independently examined these full‐text articles for compliance with the inclusion criteria and selected studies eligible for inclusion in the review. We corresponded with study investigators, as required, to clarify study eligibility or to seek further data where necessary. We resolved disagreements on study eligibility by discussion or with a third review author (JMD). See Figure 1 for the selection process documented in a PRISMA flow chart.

1.

1

Study flow diagram.

Data extraction and management

Two review authors independently extracted the data from eligible studies using a data extraction form designed and pilot‐tested by the review authors. We resolved any disagreements by discussion. Data extracted included study characteristics and outcome data. Where studies had multiple publications, the main trial report was used as the reference and additional details were derived from the secondary papers. We corresponded with study investigators for further data on methods and results, as required.

Assessment of risk of bias in included studies

Two review authors independently assessed the included studies for risk of bias using the Cochrane 'Risk of bias' assessment tool in the Cochrane Handbook for Systematic Reviews of Interventions to assess: allocation (random sequence generation and allocation concealment); blinding of participants and personnel, blinding of outcome assessors; incomplete outcome data; selective reporting and other bias (Higgins 2011). We resolved disagreements by discussion. We described all the judgements fully and presented the conclusions in the 'Risk of bias' table. The risk of bias was incorporated into the interpretation of review findings by means of sensitivity analyses.

We detected within‐trial selective reporting, such as trials failing to report obvious outcomes or reporting them in insufficient detail to allow inclusion. We sought published protocols and compared the outcomes between the protocol and the final published study.

Measures of treatment effect

For dichotomous data (e.g. live birth rates), we used the numbers of events in the control and intervention groups of each study and calculated Mantel‐Haenszel odds ratios (ORs). For continuous data (e.g. pain), we reported mean differences (MD) between the groups using change from baseline pain scores. If similar outcomes had been reported on different scales for the same outcome, we planned to calculate the standardised mean difference (SMD). We planned to reverse the direction of effect of individual studies, if required, to ensure consistency across trials. We presented 95% confidence intervals (CI) for all outcomes. Where the data to calculate ORs or SMDs were not available, we utilised the most detailed numerical data available that facilitated similar analyses of included studies (e.g. test statistics, P values). We compared the magnitude and direction of effect reported by studies with how they were presented in the review, taking account of legitimate differences.

Unit of analysis issues

The primary analysis was per woman randomised; we included per pregnancy data for some outcomes (e.g. miscarriage). We briefly summarised data that did not allow valid analysis and excluded them from the meta‐analyses. We counted multiple live births (e.g. twins or triplets) one live birth event.

Dealing with missing data

We analysed the data using an intention to treat basis, as far as possible, and attempted to obtain missing data from the original trialists. Where these were unobtainable, we undertook imputation of individual values for the primary outcomes only. Live births were assumed not to have occurred in participants without a reported outcome. For other outcomes, we analysed only the available data. We planned that any imputation undertaken would be subjected to sensitivity analysis (see Sensitivity analysis).

When studies reported sufficient detail to calculate MDs but no information on associated standard deviations (SD), we calculated a change from baseline SD using a correlation coefficient (Corr) and performed a sensitivity analysis inputting different values of Corr (0.2, 0.5 and 0.8; see the Cochrane Handbook for Systematic Reviews of Interventions Section 16.1.3.2; Higgins 2011).

Assessment of heterogeneity

We considered whether the clinical and methodological characteristics of the included studies were sufficiently similar for meta‐analysis to provide a clinically meaningful summary. We assessed statistical heterogeneity using the I2 statistic. An I2 value greater than 50% was taken to indicate substantial heterogeneity (Higgins 2011).

Assessment of reporting biases

Reporting biases arise when the dissemination of research findings is influenced by the nature and direction of results. Some types of reporting bias (e.g. publication bias, multiple publication bias, language bias) reduce the likelihood that all studies eligible for a review will be retrieved. If all eligible studies are not retrieved, the review may be biased. In view of the difficulty of detecting and correcting for publication bias and other reporting biases, the authors aimed to minimise their potential impact by ensuring a comprehensive search for eligible studies and by being alert for duplication of data. If there were 10 or more studies in an analysis, we planned to use a funnel plot to explore the possibility of small‐study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies).

Data synthesis

When studies were sufficiently similar, we combined the data using a fixed‐effect model. An increase in the odds of a particular outcome, which may be beneficial (e.g. live birth) or detrimental (e.g. adverse effects), is displayed graphically in the meta‐analysis to the right of the centre‐line and a decrease in the odds of an outcome to the left of the centre‐line.

Subgroup analysis and investigation of heterogeneity

Where data were available for primary outcomes, we planned subgroup analyses to determine the separate evidence within the following subgroups.

  1. Severity of disease.

  2. Surgical technique to excise peritoneal deposits.

  3. Surgical technique to ablate peritoneal deposits.

If we detected substantial heterogeneity, we planned to explore possible explanations in sensitivity analyses. We planned to take any statistical heterogeneity into account when interpreting the results, especially when there was any variation in the direction of effect.

Sensitivity analysis

We conducted sensitivity analyses for the primary outcomes to determine whether the conclusions were robust to arbitrary decisions made regarding the eligibility and analysis. These analyses included consideration of whether the review conclusions would have differed if:

  1. eligibility was restricted to studies without high risk of bias;

  2. a random‐effects model was adopted;

  3. alternative imputation strategies were implemented;

  4. the summary effect measure was risk ratio.

Overall quality of the body of evidence: 'Summary of findings' table

We prepared 'Summary of findings' tables using GRADEpro and Cochrane methods (GRADEpro GDT; Higgins 2011). These tables evaluated the overall quality of the body of evidence for the primary review outcomes (overall pain and live birth) and secondary outcomes (quality of life, viable intrauterine pregnancy confirmed by ultrasound, pregnancy loss (ectopic pregnancy and miscarriage) and adverse events) for the main review comparison: laparoscopic treatment of endometriosis compared with diagnostic laparoscopy.

We prepared additional Summary of Findings tables for the main review outcomes for other important comparisons: laparoscopic ablation and uterine nerve transection compared with diagnostic laparoscopy only, laparoscopic ablation compared with laparoscopic excision and laparoscopic ablation or excision with helium thermal coagulator compared with laparoscopic ablation or excision with electrodiathermy.

We used GRADE criteria (study limitations (that is risk of bias), consistency of effect, imprecision, indirectness and publication bias). We restricted the selection of outcomes for the 'Summary of findings' tables to time points that were the most clinically relevant. Judgements about evidence quality (high, moderate or low) were justified, documented and incorporated into reporting of results for each outcome.

Results

Description of studies

Results of the search

This is an update of a review first published in 2014 with 10 RCTs. An updated search was performed from July 2013 to April 2020. The search retrieved 1175 articles after removal of duplicates. A total of 23 studies were potentially eligible and were retrieved in full text. Four studies met our inclusion criteria (Di Donato 2015; Misra 2020; Roman 2018; Zullo 2003), bringing the total number of included studies to 14 (Abbott 2004; Di Donato 2015; Gad 2012; Healey 2010; Jarrell 2005; Lalchandani 2005; Marcoux 1997; Misra 2020; Moini 2012; Roman 2018; Sutton 1994; Tutunaru 2006; Wright 2005; Zullo 2003). We excluded 17 studies at this update, resulting in a total of 20 excluded studies. Two studies are ongoing (Hardcastle 2015; Mabrouk 2018), and one is awaiting classification (NCT02282943).

See: Characteristics of included studies; Characteristics of excluded studies; Characteristics of studies awaiting classification; and Characteristics of ongoing studies tables and the PRISMA flow chart (Figure 1).

Included studies

Study design and setting

Fourteen parallel design RCTs fulfilled the inclusion criteria. Nine RCTs were conducted in a single centre (Abbott 2004; Di Donato 2015; Healey 2010; Jarrell 2005; Misra 2020; Moini 2012; Sutton 1994; Wright 2005; Zullo 2003), four RCTs were conducted in multiple centres (Gad 2012; Lalchandani 2005; Marcoux 1997; Roman 2018), and the study setting was unclear in one RCT report (Tutunaru 2006). The trials were conducted in Australia (Healey 2010), Canada (Jarrell 2005; Marcoux 1997), Egypt (Gad 2012), France (Roman 2018), Italy (Di Donato 2015; Zullo 2003), Iran (Moini 2012) and the UK (Abbott 2004; Lalchandani 2005; Misra 2020; Sutton 1994; Wright 2005).

Participants

The studies randomised 1563 participants experiencing pain (Abbott 2004; Di Donato 2015; Healey 2010; Jarrell 2005; Lalchandani 2005; Misra 2020; Tutunaru 2006; Roman 2018; Sutton 1994; Wright 2005; Zullo 2003), or infertility (Gad 2012; Marcoux 1997; Moini 2012), associated with endometriosis.

Interventions
  • Comparison 1: laparoscopic treatment of endometriosis compared with diagnostic laparoscopy only:

  • Comparison 2: two RCTs compared laparoscopic ablation and uterine nerve transection with diagnostic laparoscopy only (Sutton 1994; Zullo 2003).

  • Comparison 3: two RCTs compared laparoscopic ablation with laparoscopic excision (Healey 2010; Wright 2005).

  • Comparison 4: one RCT compared laparoscopic ablation or excision with helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy (Misra 2020).

  • Comparison 5: one RCT compared conservative laparoscopic surgery with laparoscopic colorectal resection of deep infiltrating endometriosis (Roman 2018).

  • Comparison 6: one RCT compared laparoscopic ablation or excision only with laparoscopic ablation or excision and uterine suspension (Di Donato 2015).

  • Comparison 7: one RCT compared laparoscopic ablation with diagnostic laparoscopy and gonadotropin‐releasing hormone (GnRH) analogues (Lalchandani 2005).

Outcomes
Primary outcome
Overall pain

Five RCTs reported overall pain (Abbott 2004; Healey 2010; Jarrell 2005; Lalchandani 2005; Tutunaru 2006).

Overall pain measurement instruments:
  1. Abbott 2004: VAS anchored between zero (labelled no change in pain) and 100 (labelled complete relief of pain);

  2. Healey 2010: (VAS anchored between zero (labelled no pain) and 10 (labelled worst imaginable pain);

  3. Jarrell 2005: VAS between zero and 100, completed for one month at baseline and then daily for one month at three‐months intervals for the next year;

  4. Lalchandani 2005: no detailed description.

  5. Tutunaru 2006: no detailed description.

Live birth

No RCTs collected or reported live birth.

Secondary outcomes
Improvement in the most troublesome symptom

No RCTs collected or reported improvement in most troublesome symptom.

Quality of life

Four RCTs reported quality of life (Abbott 2004; Lalchandani 2005; Misra 2020; Roman 2018).

Quality of life measurement instruments:

  1. Abbott 2004: EuroQol‐5D (EQ‐5D) and 12‐item Short Form health survey (SF‐12);

  2. Lalchandani 2005: EQ‐5D and SF‐12 health survey;

  3. Misra 2020: 30‐item Endometriosis Health Profile‐30 questionnaire (EHP‐30);

  4. Roman 2018: 36‐item Short Form 36 health survey (SF‐36) and Gastrointestinal Quality of Life Index (GiQLI).

Viable intrauterine pregnancy confirmed by ultrasound

Three RCTs reported viable intrauterine pregnancy confirmed by ultrasound (Gad 2012; Marcoux 1997; Moini 2012).

Pregnancy loss

One RCT reported ectopic pregnancy (Marcoux 1997). Two RCTs reported miscarriage (Gad 2012; Marcoux 1997). No RCTs reported stillbirth or termination of pregnancy.

Gestational age at birth

No RCTs collected or reported gestational age at birth.

Birth weight

No RCTs collected or reported birth weight.

Neonatal mortality

No RCTs collected or reported neonatal mortality.

Major congenital anomaly

No RCTs collected or reported major congenital anomaly.

Adverse events

Roman 2018 reported adverse events using the Clavien Dindo Classification (Clavien 2009).

Other adverse events were reported.

No RCTs reported mortality or venous thromboembolism.

Participant satisfaction with treatment

No RCTs collected or reported participant satisfaction with treatment.

Excluded studies

Three studies (five references) were excluded from the review in 2014 for the following reasons:

  • one RCT assessed a medical adjuvant (tryptorelin) (Parazzini 1999);

  • one RCT included participants with no definitive diagnosis of endometriosis or not presenting with symptoms of pain or infertility (Soysal 2001);

  • one RCT compared a laparoscopic procedure with an open procedure for severe endometriosis (Darai 2010).

Seventeen studies (17 references) were excluded from the updated search of this review for the following reasons:

  • eight RCTs assessed a medical adjuvant (tryptorelin) (Benton 2017; Lang 2018; NCT03352076; Orazov 2019; Scioscia 2017; Yang 2019; Yin 2016; Zhao 2016);

  • three RCTs included participants with no definitive diagnosis of endometriosis (Algergawy 2016; Gallicchio 2015; Soto 2017);

  • one RCT compared a laparoscopic procedure with an open procedure for severe endometriosis (Ruan 2015);

  • one RCT compared two robotic‐assisted laparoscopic approaches (Riley 2019);

  • two RCTs assessed a wrong outcome (i.e. adhesion formation) (Di Donato 2013; Kraemer 2019);

  • one RCT had no randomisation per participant (Dehbashi 2019);

  • one RCT had a wrong comparator (diagnostic laparoscopy followed by hormone therapy with leuprorelin acetate 3.75 mg depot injected subcutaneously monthly for three months versus surgical laparoscopy without any subsequent medical treatment versus surgical laparoscopy followed by the same hormone therapy as group 1 over the same period) (Alkatout 2013).

Risk of bias in included studies

See Characteristics of included studies table, Figure 2 and Figure 3.

2.

2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

3.

3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Eight RCTs were at low risk of selection bias related to sequence generation as they used computer randomisation (Abbott 2004; Healey 2010; Jarrell 2005; Marcoux 1997; Misra 2020; Roman 2018; Sutton 1994; Zullo 2003). The remaining six RCTs did not describe the method used and were at unclear risk of bias (Di Donato 2015; Gad 2012; Lalchandani 2005; Moini 2012; Tutunaru 2006; Wright 2005).

Eight RCTs were at low risk of selection bias related to allocation concealment as they used appropriate methods (Abbott 2004; Healey 2010; Jarrell 2005; Marcoux 1997; Misra 2020; Moini 2012; Roman 2018; Wright 2005). The remaining six RCTs did not describe the method used and were at unclear risk of selection bias related to allocation concealment (Di Donato 2015; Gad 2012; Lalchandani 2005; Sutton 1994; Tutunaru 2006; Zullo 2003).

Blinding

We considered that blinding of participants and outcome observers would influence the subjective primary outcome of overall pain. It would not be possible to blind the personnel involved in surgical interventions. However, it would be possible to blind participants and outcome assessors where one laparoscopic intervention was compared to another (Abbott 2004; Di Donato 2015; Healey 2010; Jarrell 2005; Lalchandani 2005; Marcoux 1997; Misra 2020; Roman 2018; Sutton 1994; Tutunaru 2006; Wright 2005; Zullo 2003).

Six RCTs blinded both participants and outcome assessors and so were at low risk of performance and detection bias (Abbott 2004; Healey 2010; Jarrell 2005; Misra 2020; Sutton 1994; Zullo 2003). Six RCTs did not state whether participants and outcome assessors were blinded and so were at unclear risk of performance and detection bias (Di Donato 2015; Gad 2012; Lalchandani 2005; Marcoux 1997; Tutunaru 2006; Wright 2005).

We did not consider that blinding was likely to influence the findings for the remaining primary (live birth rate) or secondary outcomes (quality of life, improvement of the most troublesome symptom, viable intrauterine pregnancy confirmed by ultrasound, pregnancy loss, gestational age at birth, birth weight, neonatal mortality, major congenital anomaly, adverse events and participant satisfaction with treatment).

Four RCTs blinded participants and were deemed at low risk of performance bias (Abbott 2004; Misra 2020; Moini 2012; Zullo 2003). Three RCT blinded outcome assessors and were deemed at low risk of detection bias (Abbott 2004; Misra 2020; Zullo 2003). Three RCTs did not state whether participants and outcome assessors were blinded and so were deemed at unclear risk of performance and detection bias (Gad 2012; Lalchandani 2005; Marcoux 1997).

Incomplete outcome data

Five RCTs reported no exclusions or participants lost to follow‐up (Abbott 2004; Gad 2012; Lalchandani 2005; Roman 2018; Wright 2005). Marcoux 1997 reported a loss to follow‐up rate of 21/341 (6%) and exclusion rate of 28/341 (8%); Misra 2020 reported a loss to follow‐up rate of 37/192 (19%) and no exclusions after randomisation; Sutton 1994 reported a loss to follow‐up rate of 3/74 (4%) and exclusion rate of 11/74 (15%); and Zullo 2003 reported a loss to follow‐up rate of 3/141 (2%) and exclusion rate of 12/141 (9%) (balanced between the intervention and control groups). Four RCTs were at high risk of attrition bias because their combined losses to follow‐up and exclusion rate was over 20% (Healey 2010; Jarrell 2005; Moini 2012; Tutunaru 2006). The reported dropout rates for these RCTs were 46/178 (26%) (Healey 2010), 15/29 (52%) (Jarrell 2005), and 24/146 (16%) (Moini 2012). The exclusion rate was 29/178 (16%) (Healey 2010) and 36/146 (24%) (Moini 2012). Two RCTs did not report its losses to follow‐up or exclusions and so was at an unclear risk of attrition bias (Di Donato 2015; Tutunaru 2006).

Selective reporting

Protocols were available for two RCTs and these reported the prespecified outcomes (Abbott 2004; Moini 2012). However, Abbott 2004 did not report adverse events and Moini 2012 did not report live birth rate, so both were at unclear risk of selective reporting.

Among nine RCTs where protocols were not available, eight RCTs reported outcomes that were prestated in their methods sections (Healey 2010; Jarrell 2005; Marcoux 1997; Misra 2020; Roman 2018; Sutton 1994; Wright 2005; Zullo 2003). None reported live birth rate.

Three RCTs were conference abstracts, so the full methods and results were not described; moreover, adverse events were not reported (Di Donato 2015; Gad 2012; Tutunaru 2006). Therefore, we considered these at unclear risk of reporting bias.

Lalchandani 2005 stated that the "analysis of pain scores and success rates of the two treatment modalities will be discussed in a second paper", which was not subsequently published; moreover, this study did not report adverse events. It was rated at unclear risk of reporting bias.

In summary, as all studies failed to report live birth rates, they were rated at unclear risk of selective reporting.

Other potential sources of bias

No studies reported substantial baseline differences in prognostic factors between the treatment and control groups. We found no other potential sources of bias within the included studies.

Effects of interventions

See: Table 1; Table 2; Table 3; Table 4

Summary of findings 1. Laparoscopic treatment compared to diagnostic laparoscopy for endometriosis.

Laparoscopic treatment compared to diagnostic laparoscopy for endometriosis
Patient or population: women with endometriosis
Setting: any setting (single centre and multicentre RCTs)
Intervention: laparoscopic treatment
Comparison: diagnostic laparoscopy
Outcomes Anticipated absolute effects* (95% CI) Relative effect
(95% CI) № of participants
(studies) Quality of the evidence
(GRADE) Comments
Risk with diagnostic laparoscopy Risk with laparoscopic treatment
Overall pain scores unclear measurement instrument (6 months) The mean overall pain scores unclear measurement instrument (6 months) was 1 MD 0.9 higher
(0.31 higher to 1.49 higher) 16
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
Overall pain scores unclear measurement instrument (12 months) The mean overall pain scores unclear measurement instrument (12 months) was 0.95 MD 1.65 higher
(1.11 higher to 2.19 higher) 16
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
Live birth None of the studies reported live birth.
Quality of life EQ‐5D index summary (6 months) The mean quality of life EQ‐5D index summary (6 months) was 0.74 MD 0.03 higher
(0.12 lower to 0.18 higher) 39
(1 RCT) ⊕⊕⊝⊝
Lowb Assessed in 1 trial of women seeking pain relief.
Quality of life SF‐12 mental health component (6 months) The mean quality of life SF‐12 mental health component (6 months) was 45.3 MD 2.3 higher
(4.5 lower to 9.1 higher) 39
(1 RCT) ⊕⊕⊝⊝
Lowb Assessed in 1 trial of women seeking pain relief.
Quality of life SF‐12 physical health component (6 months) The mean quality of life SF‐12 physical health component (6 months) was 45.5 MD 2.7 higher
(2.9 lower to 8.3 higher) 39
(1 RCT) ⊕⊕⊝⊝
Lowb Assessed in 1 trial of women seeking pain relief.
Viable intrauterine pregnancy confirmed by ultrasound Study population OR 1.89
(1.25 to 2.86) 528
(3 RCTs) ⊕⊕⊕⊝
Moderatea Assessed in trials of infertile women.
186 per 1000 302 per 1000
(223 to 396)
Pregnancy loss: ectopic pregnancy per pregnancy Study population OR 1.18
(0.10 to 13.48) 100
(1 RCT) ⊕⊕⊝⊝
Lowb Assessed in 1 trial of infertile women.
27 per 1000 32 per 1000
(3 to 272)
Pregnancy loss: miscarriage per pregnancy Study population OR 0.94
(0.35 to 2.54) 112
(2 RCTs) ⊕⊕⊝⊝
Lowb Assessed in trials of infertile women.
190 per 1000 181 per 1000
(76 to 374)
Adverse events: conversion to laparotomy Study population Not estimable 341
(1 RCT)
⊕⊕⊝⊝
Lowc
Assessed in 1 trial of infertile women.
0 per 1000 0 per 1000
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; EQ‐5D: EuroQol‐5D; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial; SF‐12: 12‐item Short Form.
GRADE Working Group grades of evidenceHigh quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded once for high risk of attrition bias.
bDowngraded twice for imprecision – limited number of participants or wide confidence interval crossing the line of no effect, or both.
cDowngraded twice for imprecision – zero events; limited number of participant

Summary of findings 2. Laparoscopic ablation and uterine nerve transaction compared to diagnostic laparoscopy for endometriosis.

Laparoscopic ablation and uterine nerve transection compared to diagnostic laparoscopy for endometriosis
Patient or population: endometriosis
Setting: single centre RCT
Intervention: laparoscopic ablation and uterine nerve transection
Comparison: diagnostic laparoscopy
Outcomes Anticipated absolute effects* (95% CI) Relative effect
(95% CI) № of participants
(studies) Quality of the evidence
(GRADE) Comments
Risk with diagnostic laparoscopy Risk with laparoscopic ablation and uterine nerve transection
Adverse events Study population OR 0.33
(0.01 to 8.32) 141
(1 RCT) ⊕⊕⊝⊝
Lowa Assessed in 1 trial of women seeking pain relief.
14 per 1000 5 per 1000
(0 to 106)
There were no trials that reported on overall pain scores (at 6 and 12 months), live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy per pregnancy and miscarriage per pregnancy.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; OR: odds ratio; RCT: randomised controlled trial.
GRADE Working Group grades of evidenceHigh quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded twice for imprecision – limited number of participants and 95% confidence interval overlapped no effect.

Summary of findings 3. Laparoscopic ablation compared to laparoscopic excision for endometriosis.

Laparoscopic ablation compared to laparoscopic excision for endometriosis
Patient or population: endometriosis
Setting: single centre RCT
Intervention: laparoscopic ablation
Comparison: laparoscopic excision
Outcomes Anticipated absolute effects* (95% CI) Relative effect
(95% CI) № of participants
(studies) Quality of the evidence
(GRADE) Comments
Risk with laparoscopic excision Risk with laparoscopic ablation
Overall pain scores (reduction in VAS at 12 months) The mean overall pain scores (reduction in VAS at 12 months) was 2.9 MD 0
(1.22 lower to 1.22 higher) 103
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
There were no trials that reported on overall pain scores at 6 months, live birth, quality of life, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy per pregnancy, miscarriage per pregnancy and adverse events.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; MD: mean difference; RCT: randomised controlled trial; VAS: visual analogue scale.
GRADE Working Group grades of evidenceHigh quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded once for high risk of attrition bias.
bDowngraded twice for imprecision – limited number of participants and 95% confidence intervals crossed the threshold.

Summary of findings 4. Helium thermal coagulator compared to electrodiathermy for endometriosis.

Helium thermal coagulator compared to electrodiathermy for endometriosis
Patient or population: endometriosis
Setting: single centre RCT
Intervention: helium thermal coagulator
Comparison: electrodiathermy
Outcomes Anticipated absolute effects* (95% CI) Relative effect
(95% CI) № of participants
(studies) Quality of the evidence
(GRADE) Comments
Risk with electrodiathermy Risk with helium thermal coagulator
Quality of life (9 months) – EHP‐30 pain The mean quality of life (9 months) – EHP‐30 pain was 35.19 MD 6.68 higher
(3.07 lower to 16.43 higher) 119
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
Quality of life (9 months) – EHP‐30 control and powerlessness The mean quality of life (9 months) – EHP‐30 control and powerlessness was 44.79 MD 4.79 higher
(6.92 lower to 16.5 higher) 119
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
Quality of life (9 months) – EHP‐30 emotional well‐being The mean quality of life (9 months) – EHP‐30 emotional well‐being was 39.1 MD 6.17 higher
(3.95 lower to 16.29 higher) 119
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
Quality of life (9 months) – EHP‐30 social support The mean quality of life (9 months) – EHP‐30 social support was 44.27 MD 5.62 higher
(6.21 lower to 17.45 higher) 119
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
Quality of life (9 months) – EHP‐30 self‐image The mean quality of life (9 months) – EHP‐30 self‐image was 43.47 MD 3.56 higher
(8.69 lower to 15.81 higher) 119
(1 RCT) ⊕⊝⊝⊝
Very lowa,b Assessed in 1 trial of women seeking pain relief.
Adverse events Study population Not estimable 192
(1 RCT) ⊕⊝⊝⊝
Very lowa,c Assessed in 1 trial of women seeking pain relief.
0 per 1000 0 per 1000
(0 to 0)
There were no trials that reported on overall pain scores (at 6 and 12 months), live birth, viable intrauterine pregnancy confirmed by ultrasound, ectopic pregnancy per pregnancy and miscarriage per pregnancy.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; MD: mean difference; EHP‐30: 30‐item Endometriosis Health Profile; RCT: randomised controlled trial.
GRADE Working Group grades of evidenceHigh quality: we are very confident that the true effect lies close to that of the estimate of the effect.
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

aDowngraded once for high risk of attrition bias.
bDowngraded twice for imprecision – limited number of participants and 95% confidence intervals crossed the threshold.

c Downgraded twice for imprecision – zero events, limited number of participants

1. Laparoscopic treatment of endometriosis compared with diagnostic laparoscopy

Four RCTs compared laparoscopic ablation or excision with diagnostic laparoscopy only (Gad 2012; Marcoux 1997; Moini 2012; Tutunaru 2006). Two RCTs compared laparoscopic excision with diagnostic laparoscopy only (Abbott 2004; Jarrell 2005). See Table 1.

Primary outcomes
Overall pain

We are uncertain of the effect of laparoscopic excision on overall pain scores compared to diagnostic laparoscopy only at six months (MD on 0 to 100 VAS 0.90, 95% CI 0.31 to 1.49; 1 RCT, 16 participants; very low quality evidence) and at 12 months (MD 1.65, 95% CI 1.11 to 2.19; 1 RCT, 16 participants; very low quality evidence; Analysis 1.1; Analysis 1.2; Figure 4). Sensitivity analysis was undertaken by trying different values of Corr (0.2, 0.5, 0.8), which did not alter the overall effect. A positive value means pain relief (the higher the score, the more pain relief) and a negative value reflects pain increase (the lower the score, the worse the increase in pain).

1.1. Analysis.

1.1

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 1: Overall pain scores unclear measurement instrument (6 months)

1.2. Analysis.

1.2

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 2: Overall pain scores unclear measurement instrument (12 months)

4.

4

Forest plot of comparison: 1 Laparoscopic treatment versus diagnostic laparoscopy, outcome: 1.2 Overall pain scores unclear measurement instrument (12 months).

Abbott 2004 reported a significantly greater number of women with overall pain improvement after laparoscopic surgery (excision) compared to diagnostic laparoscopy only six months after surgery (P = 0.012). These data could not be included in the meta‐analysis as there were insufficient data presented to impute a change‐from‐baseline SD.

Tutunaru 2006 stated overall pain was collected using pain scales; however, they did not report these data in the results or conclusions.

Live birth

No RCTs reported live birth.

Secondary outcomes
Improvement in most troublesome symptom

No RCTs reported improvement in most troublesome symptom.

Quality of life

We are uncertain of the effect of laparoscopic excision associated with differences in reported quality of life, measured using the EQ‐SD (MD 0.03, 95% CI –0.12 to 0.18, 1 RCT, 39 participants; low quality evidence; Analysis 1.3), SF‐12 mental health component (MD 2.30, 95% CI –4.50 to 9.10, 1 RCT, 39 participants; low quality evidence; Analysis 1.4), or SF‐12 physical health component (MD 2.70, 95% CI –2.90 to 8.30; 1 RCT, 39 participants; low quality evidence; Analysis 1.5), when compared with diagnostic laparoscopy.

1.3. Analysis.

1.3

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 3: Quality of life EQ‐5D index summary (6 months)

1.4. Analysis.

1.4

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 4: Quality of life SF‐12 mental health component (6 months)

1.5. Analysis.

1.5

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 5: Quality of life SF‐12 physical health component (6 months)

Viable pregnancy confirmed by ultrasound

Laparoscopic ablation or excision probably increases pregnancy rate compared to diagnostic laparoscopy only (OR 1.89, 95% CI 1.25 to 2.86, 3 RCTs, 528 participants; I2 = 0%; moderate quality evidence; Analysis 1.6; Figure 5). Sensitivity analysis excluding poor quality studies (Gad 2012; Moini 2012) did not affect the results of the main analysis for this outcome. No subgroup analysis was possible.

1.6. Analysis.

1.6

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 6: Viable intrauterine pregnancy confirmed by ultrasound

5.

5

Forest plot of comparison: 1 Laparoscopic treatment versus diagnostic laparoscopy, outcome: 1.6 Viable intrauterine pregnancy confirmed by ultrasound.

Pregnancy loss: ectopic pregnancy

We are uncertain of the effect of laparoscopic ablation or excision on ectopic pregnancy rate compared to diagnostic laparoscopy only (OR 1.18, 95% CI 0.10 to 13.48; 1 RCT, 100 participants; low quality evidence; Analysis 1.7).

1.7. Analysis.

1.7

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 7: Ectopic pregnancy per pregnancy

Pregnancy loss: miscarriage

We are uncertain of the effect of laparoscopic ablation or excision on miscarriage rate compared to diagnostic laparoscopy only (OR 0.94, 95% CI 0.35 to 2.54; 2 RCTs, 112 participants; low quality evidence; Analysis 1.8).

1.8. Analysis.

1.8

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 8: Miscarriage per pregnancy

Stillbirth and termination of pregnancy were not reported.

Gestational age at birth

No RCTs reported gestational age at birth.

Birth weight

No RCTs reported birth weight.

Neonatal mortality

No RCTs reported neonatal mortality.

Major congenital anomaly

No RCTs reported major congenital anomaly.

Adverse events

We are uncertain of the effect of laparoscopic ablation or excision on solid organ injury compared to diagnostic laparoscopy only (OR 3.00, 95% CI 0.11 to 78.27, 1 RCT, 39 participants, low quality evidence; Analysis 1.9). We are uncertain of the effect of laparoscopic ablation or excision on blood transfusion compared to diagnostic laparoscopy only (OR 3.00, 95% CI 0.11 to 78.27, 1 RCT, 39 participants, low quality evidence; Analysis 1.9). We are uncertain of the effect of laparoscopic ablation or excision on vascular injury compared to diagnostic laparoscopy only (OR 0.33, 95% CI 0.01 to 8.05, 2 RCT, 487 participants, low quality evidence; Analysis 1.9). We are uncertain of the effect of laparoscopic ablation or excision on visceral injury compared to diagnostic laparoscopy only (OR 2.97, 95% CI 0.12 to 73.3, 2 RCT, 487 participants, low quality evidence; Analysis 1.9). We are uncertain of the effect of laparoscopic ablation or excision on infection compared to diagnostic laparoscopy only (OR 1.68, 95% CI 0.60 to 4.72, 2 RCT, 487 participants, low quality evidence; Analysis 1.9). No conversions to laparotomy were reported in both groups (1 RCT, 341 participants; Analysis 1.9). No RCTs reported on mortality and venous thromboembolism.

1.9. Analysis.

1.9

Comparison 1: Laparoscopic treatment versus diagnostic laparoscopy, Outcome 9: Adverse events

Participant satisfaction with treatment

No RCTs reported participant satisfaction with treatment.

2. Laparoscopic ablation and uterine nerve transection compared with diagnostic laparoscopy only

Two RCTs compared laparoscopic ablation and uterine nerve transection with diagnostic laparoscopy only (Sutton 1994; Zullo 2003). See Table 2.

Primary outcomes
Overall pain

No RCTs reported overall pain.

Live birth

No RCTs reported live birth.

Secondary outcomes
Improvement in most troublesome symptom

No RCTs reported improvement in most troublesome symptom.

Quality of life

No RCTs reported quality of life.

Viable pregnancy confirmed by ultrasound

No RCTs reported viable pregnancy confirmed by ultrasound.

Pregnancy loss: ectopic pregnancy

No RCTs reported ectopic pregnancy.

Pregnancy loss: miscarriage

No RCTs reported miscarriage.

Gestational age at birth

No RCTs reported gestational age at birth.

Birth weight

No RCTs reported birth weight.

Neonatal mortality

No RCTs reported neonatal mortality.

Major congenital anomaly

No RCTs reported major congenital anomaly.

Adverse events

There was insufficient evidence to determine whether there was a difference between laparoscopic ablation and uterine nerve transection compared with diagnostic laparoscopy in adverse event (more specifically vascular injuries) (OR 0.33, 95% CI 0.01 to 8.32; 1 RCT, 141 participants; low quality evidence; Analysis 2.1).

2.1. Analysis.

2.1

Comparison 2: Laparoscopic ablation and uterine nerve transection versus diagnostic laparoscopy, Outcome 1: Adverse events

Participant satisfaction with treatment

No RCTs reported participant satisfaction with treatment.

3. Laparoscopic ablation compared with laparoscopic excision

Two RCTs compared laparoscopic ablation with laparoscopic excision (Healey 2010; Wright 2005). See Table 3.

Primary outcome
Overall pain

There was insufficient evidence to determine whether there was a difference in overall pain, measured at 12 months, for laparoscopic ablation compared with laparoscopic excision (MD 0, 95% CI –1.22 to 1.22; 1 RCT, 103 participants; very low quality evidence; Analysis 3.1; Figure 6).

3.1. Analysis.

3.1

Comparison 3: Laparoscopic ablation versus laparoscopic excision, Outcome 1: Overall pain scores (reduction in VAS at 12 months)

6.

6

Forest plot of comparison: 3 Laparoscopic ablation versus laparoscopic excision, outcome: 3.1 Overall pain scores (reduction in visual analogue scale score at 12 months).

Live birth

No RCTs reported live birth.

Secondary outcomes
Improvement in most troublesome symptom

No RCTs reported improvement in most troublesome symptom.

Quality of life

No RCTs reported quality of life.

Viable pregnancy confirmed by ultrasound

No RCTs reported viable pregnancy confirmed by ultrasound.

Pregnancy loss: ectopic pregnancy

No RCTs reported ectopic pregnancy.

Pregnancy loss: miscarriage

No RCTs reported miscarriage.

Gestational age at birth

No RCTs reported gestational age at birth.

Birth weight

No RCTs reported birth weight.

Neonatal mortality

No RCTs reported neonatal mortality.

Major congenital anomaly

No RCTs reported major congenital anomaly.

Adverse events

Adverse events were not collected or reported.

Participant satisfaction with treatment

Participant satisfaction with treatment was not collected or reported.

4. Laparoscopic ablation or excision with helium thermal coagulator compared with laparoscopic ablation or excision with electrodiathermy

One RCT compared laparoscopic ablation or excision with helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy (Misra 2020). See Table 4.

Primary outcome
Overall pain

The RCT did not report overall pain.

Live birth

The RCT did not report live birth.

Secondary outcomes
Improvement in most troublesome symptom

The RCT did not report improvement in most troublesome symptom.

Quality of life

When comparing laparoscopic ablation or excision using helium thermal coagulator with laparoscopic ablation or excision with electrodiathermy there was insufficient evidence to determine differences in reported quality of life, measured using the EHP‐30 at nine months, when considering the following components: pain (MD 6.68, 95% CI –3.07 to 16.43; 1 RCT, 119 participants; very low quality evidence), control and powerlessness (MD 4.79, 95% CI –6.92 to 16.50; 1 RCT, 119 participants; very low quality evidence), emotional well‐being (MD 6.17, 95% CI –3.95 to 16.29; 1 RCT, 119 participants; very low quality evidence), social support (MD 5.52, 95% CI –6.21 to 17.45; 1 RCT, 119 participants; very low quality evidence), and self‐image (MD 3.56, 95% CI –8.69 to 15.81; 1 RCT, 119 participants; very low quality evidence).

Viable pregnancy confirmed by ultrasound

The RCT did not report viable pregnancy confirmed by ultrasound.

Pregnancy loss: ectopic pregnancy

The RCT did not report ectopic pregnancy.

Pregnancy loss: miscarriage

The RCT did not report miscarriage.

Gestational age at birth

The RCT did not report gestational age at birth.

Birth weight

The RCT did not report birth weight.

Neonatal mortality

The RCT did not report neonatal mortality.

Major congenital anomaly

The RCT did not report major congenital anomaly.

Adverse events

Misra 2020 reported no visceral injuries.

Participant satisfaction with treatment

The RCT did not report participant satisfaction with treatment.

5. Conservative laparoscopic surgery compared with laparoscopic colorectal resection of deep infiltrating endometriosis.

One RCT compared conservative laparoscopic surgery with laparoscopic colorectal resection of deep infiltrating endometriosis (Roman 2018).

Primary outcome
Overall pain

Overall pain was not reported.

Live birth

The RCT did not report live birth.

Secondary outcomes
Improvement in most troublesome symptom

The RCT did not report improvement in most troublesome symptom.

Quality of life

There was insufficient evidence to determine differences in quality of life when comparing conservative laparoscopic surgery with laparoscopic colorectal resection of deep infiltrating endometriosis (Roman 2018). These data could not be included in the meta‐analysis as it was reported as cumulative distribution functions.

Viable pregnancy confirmed by ultrasound

The RCT did not report viable pregnancy confirmed by ultrasound.

Pregnancy loss: ectopic pregnancy

The RCT did not report ectopic pregnancy.

Pregnancy loss: miscarriage

The RCT did not report miscarriage.

Gestational age at birth

The RCT did not report gestational age at birth.

Birth weight

The RCT did not report birth weight.

Neonatal mortality

The RCT did not report neonatal mortality.

Major congenital anomaly

The RCT did not report major congenital anomaly.

Adverse events

Roman 2018 reported adverse events using Clavien Dindo Classification (Clavien 2009). There were insufficient data to include in this meta‐analysis as individual adverse events could not be consistently determined.

Participant satisfaction with treatment

The RCT did not report participant satisfaction with treatment.

6. Laparoscopic ablation or excision compared with laparoscopic ablation or excision and uterine suspension

One RCT compared laparoscopic ablation or excision with laparoscopic ablation or excision and uterine suspension but reported no primary or secondary outcomes (Di Donato 2015).

7. Laparoscopic ablation compared with diagnostic laparoscopy and gonadotropin‐releasing hormone analogues

One RCT compared laparoscopic ablation with diagnostic laparoscopy and GnRH analogues (Lalchandani 2005).

Primary outcomes
Overall pain

Lalchandani 2005 stated overall pain was collected using analogue pain score sheets. They did not report these data in the results or conclusions.

Live birth

The RCT did not report live birth.

Secondary outcomes
Improvement in most troublesome symptom

The RCT did not report improvement in most troublesome symptom.

Quality of life

Lalchandani 2005 stated quality of life was collected using the EQ‐5D and SF‐12 health survey. They did not report these data in the results or conclusions.

Viable pregnancy confirmed by ultrasound

The RCT did not report viable pregnancy confirmed by ultrasound.

Pregnancy loss: ectopic pregnancy

The RCT did not report ectopic pregnancy.

Pregnancy loss: miscarriage

The RCT did not report miscarriage.

Gestational age at birth

The RCT did not report gestational age at birth.

Birth weight

The RCT did not report birth weight.

Neonatal mortality

The RCT did not report neonatal mortality.

Major congenital anomaly

The RCT did not report major congenital anomaly.

Adverse events

The RCT did not report adverse events.

Participant satisfaction with treatment

The RCT did not report participant satisfaction with treatment.

Publication bias

We were unable to construct a funnel plot to assess publication bias because there were insufficient studies reporting the same comparison.

Discussion

Summary of main results

It is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis.

There is moderate quality evidence that laparoscopic surgery increases viable intrauterine pregnancy rates confirmed by ultrasound in couples with otherwise unexplained infertility. Three trials reported viable intrauterine pregnancy confirmed by ultrasound (Gad 2012; Marcoux 1997; Moini 2012). Gad 2012 reported data for 18 months after laparoscopy or up to 20 weeks of pregnancy. If pregnancy did not occur within 18 months of randomisation, women received three cycles of superovulation with intrauterine insemination as co‐treatment. Only data of the 18 months of randomisation were included in the meta‐analysis (i.e. without the results of the three cycles of superovulation with intrauterine insemination). Marcoux 1997 asked women and their physicians to avoid any medical or surgical treatment for infertility or endometriosis. Nevertheless, the type and date of any cointerventions were documented. IVF with or without intrauterine insemination was a cointervention in one woman in the laparoscopic surgery group and in two women in the diagnostic laparoscopy group; none resulted in pregnancy. Four of 79 women (whose pregnancies lasted 20 weeks), all in the diagnostic laparoscopy group, reported a cointervention during the cycle of conception (clomiphene citrate therapy in two women, and superovulation and intrauterine insemination in one woman) or during the preceding cycle (cyst excision in one woman). The reported pregnancies were all non‐assisted reproductive technology pregnancies. If these cointerventions contributed to the occurrence of the pregnancies, there would be a slight underestimation of the effect of laparoscopic surgery. Moini 2012 excluded women using medical treatment for endometriosis or infertility from the study.

There is currently no evidence of a difference when laparoscopic ablation is compared with laparoscopic excision with regard to overall pain. No studies were of sufficient power to assess safety.

Overall completeness and applicability of evidence

The evidence for each comparison was limited.

There were only a few women diagnosed with pain associated with severe endometriosis included in the meta‐analysis and therefore any conclusions regarding treatment of severe endometriosis should be made with caution. Most researchers in this area have found it difficult to consider a randomised trial for severe endometriosis due to the associated pain symptoms and need for intervention. This is an area that could be explored by comparing the efficacy of different laparoscopic techniques or medical interventions. No trials were included with participants experiencing infertility associated with severe endometriosis. The management of infertility associated with severe endometriosis is complex and referral to a centre with the necessary expertise is strongly recommended. This is an area that could be explored further by comparing different surgical interventions (with reporting of the endometriosis fertility index score (Adamson 2010)) with other treatments including IVF.

Endometriosis is considered a chronic condition and the included RCTs had follow‐up durations ranging from three to 18 months. Observational studies have reported a high reoccurrence and reintervention rate following surgical intervention over a three‐ to five‐year follow‐up period following surgical intervention (Abbott 2003). No conclusions can be made with regards to the efficacy of interventions assessed within this review in the longer term. Future research should ensure adequate follow‐up, with a suggested period of five years.

We do not currently have published RCTs available which consider the effectiveness and safety of laparoscopic surgery compared to holistic or medical interventions for pain associated with endometriosis. There are many clinical trials of holistic or medical interventions which indicate that they can relieve pain, but these are usually comparisons of alternative regimens rather than comparisons against laparoscopic surgery.

Quality of the evidence

There were few studies for each comparison and meta‐analysis could rarely be performed. When performed, heterogeneity in the analyses was low.

Using GRADE methods of assessment, the quality of the evidence for effectiveness outcomes was low or very low for most comparisons, denoting that further research is very likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Reasons for downgrading the quality of the evidence included risk of bias in the primary studies (e.g. failure to fully describe methods of randomisation and allocation concealment, and risk of attrition bias) and imprecision due to small sample sizes. Evidence on miscarriage was of low quality. There was insufficient evidence to reach any conclusions on other adverse outcomes (see Table 1).

This review was prepared with reference to recommendations developed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) (Dworkin 2005). They recommend pain should be collected using continuous measures, specifically a 11 point (0 to 10) numerical rating scale of pain intensity. We only included data that were collected using continuous measures within our meta‐analysis. This approach was supported by our protocol (Duffy 2014a).

Potential biases in the review process

To prevent bias in the review process, the search was guided and developed by the CGFG. We applied no limitations such as a publication type, language or date restrictions. Two review authors independently conducted study selection, 'Risk of bias' assessment and data collection. We resolved any disagreements by discussion with a third review author. The main bias remained the issue of multiple comparisons and small number of trials, making extrapolation difficult. There was a lack of consistency in the outcome measures used in trials, which led to difficulties in combining data in a suitable meta‐analysis and thus made it difficult to draw clinically relevant conclusions. The conflicts of interests for all review authors were stated and limited to academic activities.

There was limited reporting of the core outcome set for endometriosis (Duffy 2020a). The core outcome set was developed using formal consensus methods involving 116 healthcare professionals, 32 researchers and 206 women with endometriosis from 29 countries. It was developed to highlight the outcomes perceived as most important by healthcare professionals, researchers and women with endometriosis, and assist funding organisations to prioritise research funding, help researchers to design future research and improve the reporting of research in medical journals. Several funding bodies mandate the collection of core outcome sets including the National Institute for Health Research (UK) and Horizon 2020 (EU). Over 80 speciality journals, many of which commonly publish endometriosis research, support the development and implementation of core outcomes. The standardised collection and reporting of the core outcome set should ensure future Cochrane Reviews can undertake pair‐wise meta‐analysis efficiently and engage with more sophisticated methods including individual participant data meta‐analysis and network meta‐analysis (Duffy 2019). Significant benefits will be achieved for women with endometriosis if secondary research can be undertaken prospectively, efficiently and harmoniously (Duffy 2017b).

Agreements and disagreements with other studies or reviews

Several national and international organisations have produced guidelines concerning the management of pain associated with endometriosis (Hirsch 2018). The National Institute for Health and Care Excellence (NICE) recommends laparoscopic treatment of peritoneal endometriosis which is not involving the bowel, bladder or ureter for women experiencing pain (NICE 2017). The European Society of Human Reproduction and Embryology (ESHRE) recommends ablation or excision of peritoneal disease for treatment of pain associated with endometriosis (Dunselman 2014). The Society of Obstetricians and Gynaecologist of Canada recommend laparoscopic treatment of pain associated with endometriosis following unsuccessful medical treatment (Leyland 2010). All guidelines recommend laparoscopic treatment of minimal or mild endometriosis in women experiencing infertility associated with endometriosis (Dunselman 2014; Leyland 2010; NICE 2017).

Based on the results of this review, the effect of surgery on pain remains uncertain; however, only one RCT reported differences in overall pain using daily pain measurement at different time points (Jarrell 2005). The other trials reporting on overall pain mentioned pain improvement (Abbott 2004), or detailed description was not available (Lalchandani 2005; Tutunaru 2006). These results should be interpreted carefully since the quality of the evidence is very low. The decision to perform surgery for pain should be considered carefully in a shared patient–clinician decision‐making after discussing/trying conservative treatment. In the treatment of endometriosis related infertility, this review agrees with the existing guidelines.

Authors' conclusions

Implications for practice.

Compared to diagnostic laparoscopy only, it is uncertain whether laparoscopic surgery reduces overall pain associated with minimal to severe endometriosis. There is moderate quality evidence that laparoscopic surgery improves viable intrauterine pregnancy confirmed by ultrasound associated with minimal to mild endometriosis when compared to diagnostic laparoscopy alone. There is very low quality evidence that laparoscopic excision and ablation are similarly effective in relieving pain, though there was only one relevant study. It is not possible to draw conclusions with regards to the treatment of severe endometriosis, which specific laparoscopic surgical intervention is most effective, or whether other holistic or medical treatment modalities are more effective than laparoscopic surgery. No conclusions can be made with regards to adverse events. Careful participant selection, adequate surgical experience and appropriate equipment are important in ensuring that these techniques are usefully applied. All decisions regarding management of pain and other symptoms associated with endometriosis should be made following detailed discussion with the women of all available options.

Implications for research.

There are very few trials in this area and further trials are required focusing on different laparoscopic techniques, newer technologies including robotic surgery and different subtypes of endometriosis, for example, superficial peritoneal, ovarian and deep endometriosis. Further research is required comparing laparoscopic interventions with holistic and medical interventions. Trials should be of high methodological quality, including the routine collection and reporting of the core outcome set for endometriosis, adequately powered for the primary outcome which should be improvement in quality of life, and with five year follow‐up.

What's new

Date Event Description
5 June 2020 New citation required and conclusions have changed The addition of new studies has led to a change in the conclusions of the review
5 June 2020 New search has been performed We updated the review. We added 4 new studies and we implemented the core outcome set for endometriosis.

History

Protocol first published: Issue 3, 2014
Review first published: Issue 4, 2014

Notes

This review is an update of an existing review (Duffy 2014b). Other versions have been previously published (Jacobson 2001; Jacobson 2002; Jacobson 2009; Jacobson 2010).

Acknowledgements

We would like to thank the Cochrane Gynaecology and Fertility Review Group who assisted us with this review; the National Institute of Health Research, UK, which provided funding to complete this review; and Kirana Arambage, David Barlow, Frederico Correa, Ray Garry, Cindy Farquhar, David Olive and Tal Jacobson for contributing to previous versions of the review.

We would like to thank Rik van Eekelen, Edgardo Somigliana, Velja Mijatovic, and co‐ordinating editor Madelon van Wely for their valuable comments during the peer review process.

Appendices

Appendix 1. Cochrane Gynaecology and Fertility Group specialised register search strategy

PROCITE platform

Searched 20 April 2020

Keywords CONTAINS "laparoscopic procedure" or "laparoscopic surgery" or "laparoscopic surgical treatment" or "laparoscopic techniques" or "laparoscopic treatment" or "laparoscopy" or "*Surgical‐Procedures,‐Laparoscopic" or "minor gynecological surgery " or "laparoscopic procedure" or "laparoscopic surgery" or "laparoscopic surgical treatment" or "laparoscopic techniques" or "laparoscopic treatment" or "laparoscopy" or "*Surgical‐Procedures,‐Laparoscopic" or "minor gynecological surgery " or "laparoscopic uterine nerve ablation"or "Laparoscopic" or "laparoscopic excision" or Title CONTAINS "laparoscopic procedure" or "laparoscopic surgery" or "laparoscopic surgical treatment" or "laparoscopic techniques" or "laparoscopic treatment" or "laparoscopy" or "laparoscopic procedure" or "laparoscopic surgery" or "laparoscopic surgical treatment" or "laparoscopic techniques" or "laparoscopic treatment" or "laparoscopy" or "laparoscopic uterine nerve ablation"or "Laparoscopic" or"laparoscopic excision"

AND

Keywords CONTAINS "*Endometriosis" or "Endometriosis‐Symptoms" or "endometriosis scores" or "endometriosis‐outcome" or "adenomyosis" or "pelvic pain" or "chronic pelvic pain" or "dyschezia" or "dysmenorrhea" or "dysmenorrhoea" or "dyspareunia" or "endometriosis" or "endometrioma" or "endometrioma wall stripping" or Title CONTAINS "*Endometriosis" or "Endometriosis‐Symptoms" or "endometriosis scores" or "endometriosis‐outcome" or "adenomyosis" or "pelvic pain" or "chronic pelvic pain" or "dyschezia" or "dysmenorrhea" or "dysmenorrhoea" or "dyspareunia" or "endometriosis" or "endometrioma" or "endometrioma wall stripping"

(432 records)

Appendix 2. CENTRAL via Cochrane Register of Studies Online (CRSO) search strategy

Web platform

Searched 20 April 2020

#1 MESH DESCRIPTOR Hand‐Assisted Laparoscopy EXPLODE ALL TREES 13

#2 MESH DESCRIPTOR Laparoscopy EXPLODE ALL TREES 5457

#3 MESH DESCRIPTOR Minimally Invasive Surgical Procedures EXPLODE ALL TREES 26947

#4 MESH DESCRIPTOR Lasers EXPLODE ALL TREES 2053

#5 MESH DESCRIPTOR Diathermy EXPLODE ALL TREES 1032

#6 MESH DESCRIPTOR Robotics EXPLODE ALL TREES 566

#7 MESH DESCRIPTOR Surgery, Computer‐Assisted EXPLODE ALL TREES 901

#8 Laparoscop*:TI,AB,KY 18904

#9 celioscop*:TI,AB,KY 20

#10 peritoneoscop*:TI,AB,KY 25

#11 LUNA:TI,AB,KY 45

#12 (presacral neurectom*):TI,AB,KY 14

#13 ( (minimal* adj5 surg*)):TI,AB,KY 2952

#14 laser:TI,AB,KY 17489

#15 diathermy:TI,AB,KY 734

#16 plasmajet:TI,AB,KY 15

#17 (plasma jet):TI,AB,KY 1

#18 excision:TI,AB,KY 5220

#19 microlaparoscop*:TI,AB,KY 25

#20 minilaparoscop*:TI,AB,KY 54

#21 (Computer‐Assisted Surg*):TI,AB,KY 216

#22 (da vinci):TI,AB,KY 303

#23 (keyhole adj3 surg*):TI,AB,KY 44

#24 Robot:TI,AB,KY 2353

#25 ( remote surg*):TI,AB,KY 2

#26 microsurg*:TI,AB,KY 1085

#27 (minimally invasive):TI,AB,KY 5149

#28 (ablation or ablative):TI,AB,KY 8447

#29 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17 OR #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 75690

#30 MESH DESCRIPTOR Endometriosis EXPLODE ALL TREES 791

#31 endometrio*:TI,AB,KY 2545

#32 dyschezia:TI,AB,KY 36

#33 dyspareunia:TI,AB,KY 1002

#34 #30 OR #31 OR #32 OR #33 3357

#35 #29 AND #34 1032

Appendix 3. MEDLINE search strategy

Ovid platform

Searched from 1946 to 20 April 2020

1 exp Laparoscopy/ (96810)
2 Laparoscop$.ti,ab,sh. (137552)
3 celioscop$.tw. (556)
4 peritoneoscop$.tw. (754)
5 exp Surgical Procedures, Minimally Invasive/ (509845)
6 Lasers/ (36075)
7 exp Diathermy/ (15347)
8 LUNA.tw. (890)
9 presacral neurectom$.tw. (108)
10 (minimal$ adj5 surg$).tw. (26269)
11 laser$.tw. (267148)
12 diathermy.tw. (2961)
13 plasmajet.tw. (27)
14 plasma jet.tw. (426)
15 excision.tw. (115517)
16 microlaparoscop$.tw. (144)
17 minilaparoscop$.tw. (222)
18 exp Robotics/ (27259)
19 exp Surgery, Computer‐Assisted/ (24262)
20 Computer‐Assisted Surg$.tw. (1114)
21 da vinci.tw. (2992)
22 (keyhole adj3 surg$).tw. (156)
23 Robot$.tw. (42627)
24 remote surg$.tw. (127)
25 microsurg$.tw. (25362)
26 minimally invasive.tw. (64158)
27 (ablation or ablative).tw. (97470)
28 or/1‐27 (1095736)
29 exp Endometriosis/ (21497)
30 endometrio$.tw. (29847)
31 dyschezia.tw. (292)
32 dyspareunia.tw. (3850)
33 or/29‐32 (36848)
34 28 and 33 (8166)
35 randomized controlled trial.pt. (504013)
36 controlled clinical trial.pt. (93621)
37 randomized.ab. (476153)
38 randomised.ab. (95214)
39 placebo.tw. (212516)
40 clinical trials as topic.sh. (190790)
41 randomly.ab. (331201)
42 trial.ti. (216564)
43 (crossover or cross‐over or cross over).tw. (84229)
44 or/35‐43 (1346935)
45 exp animals/ not humans.sh. (4690983)
46 44 not 45 (1239668)
47 34 and 46 (668)

Appendix 4. Embase search strategy

Ovid platform

Searched from 1980 to 20 April 2020

1 exp Laparoscopy/ (155288)
2 Laparoscop$.tw. (197919)
3 celioscop$.tw. (311)
4 peritoneoscop$.tw. (671)
5 exp minimally invasive surgery/ (41001)
6 exp laser/ (136863)
7 exp diathermy/ (4529)
8 Diathermy.tw. (3139)
9 LUNA.tw. (1502)
10 presacral neurectom$.tw. (111)
11 laser$.tw. (271911)
12 plasmajet.tw. (85)
13 plasma jet.tw. (431)
14 microlaparoscop$.tw. (198)
15 minilaparoscop$.tw. (358)
16 exp robotics/ (38234)
17 exp computer assisted surgery/ (12442)
18 Computer‐Assisted Surg$.tw. (1318)
19 da vinci.tw. (5306)
20 (keyhole adj3 surg$).tw. (209)
21 Robot$.tw. (66732)
22 remote surg$.tw. (161)
23 microsurg$.tw. (29482)
24 uterine nerve ablation$.tw. (39)
25 minimally invasive.tw. (95939)
26 (ablation or ablative).tw. (147697)
27 exp hand assisted laparoscopy/ (794)
28 or/1‐27 (809394)
29 exp endometriosis/ (35411)
30 endometrio$.tw. (43106)
31 dyschezia.tw. (591)
32 dyspareunia.tw. (7193)
33 or/29‐32 (55100)
34 28 and 33 (13845)
35 Clinical Trial/ (962466)
36 Randomized Controlled Trial/ (595291)
37 exp randomization/ (86651)
38 Single Blind Procedure/ (38544)
39 Double Blind Procedure/ (168458)
40 Crossover Procedure/ (62718)
41 Placebo/ (335076)
42 Randomi?ed controlled trial$.tw. (225272)
43 Rct.tw. (36438)
44 random allocation.tw. (1994)
45 randomly allocated.tw. (34663)
46 allocated randomly.tw. (2518)
47 (allocated adj2 random).tw. (811)
48 Single blind$.tw. (24379)
49 Double blind$.tw. (200831)
50 ((treble or triple) adj blind$).tw. (1124)
51 placebo$.tw. (299940)
52 prospective study/ (592520)
53 or/35‐52 (2165499)
54 case study/ (67961)
55 case report.tw. (397511)
56 abstract report/ or letter/ (1090355)
57 or/54‐56 (1545507)
58 53 not 57 (2112407)
59 34 and 58 (2101)

Appendix 5. PsycINFO search strategy

Ovid platform

Searched from 1806 to 20 April 2020

1 exp Surgery/ (70546)
2 Laparoscop$.tw. (495)
3 uterine nerve ablation$.tw. (0)
4 LUNA.tw. (132)
5 presacral neurectom$.tw. (0)
6 (minimal$ adj5 surg$).tw. (213)
7 laser$.tw. (3371)
8 diathermy.tw. (30)
9 exp Robotics/ (7398)
10 Computer‐Assisted Surg$.tw. (8)
11 Robot$.tw. (8043)
12 (minimal$ adj2 invasi$).tw. (625)
13 microsurg$.tw. (234)
14 (ablation or ablative).tw. (4260)
15 or/1‐14 (87756)
16 exp Gynecological Disorders/ (1802)
17 endometrio$.tw. (286)
18 dyschezia.tw. (7)
19 dyspareunia.tw. (585)
20 or/16‐19 (2549)
21 15 and 20 (160)
22 random.tw. (57882)
23 control.tw. (441722)
24 double‐blind.tw. (22768)
25 clinical trials/ (11612)
26 placebo/ (5570)
27 exp Treatment/ (1037352)
28 or/22‐27 (1432049)
29 21 and 28 (149)

Appendix 6. CINAHL search strategy

EBSCO platform

Searched from 1961 to 20 April 2020

# Query Results
S42 S29 AND S41 313
S41 S30 OR S31 OR S32 OR S33 OR S34 OR S35 OR S36 OR S37 OR S38 OR S39 OR S40 1,593,513
S40 TX allocat* random* 13,167
S39 (MH "Quantitative Studies") 30,319
S38 (MH "Placebos") 13,668
S37 TX placebo* 70,955
S36 TX random* allocat* 13,167
S35 (MH "Random Assignment") 67,791
S34 TX randomi* control* trial* 219,908
S33 TX ( (singl* n1 blind*) or (singl* n1 mask*) ) or TX ( (doubl* n1 blind*) or (doubl* n1 mask*) ) or TX ( (tripl* n1 blind*) or (tripl* n1 mask*) ) or TX ( (trebl* n1 blind*) or (trebl* n1 mask*) ) 1,213,027
S32 TX clinic* n1 trial* 293,276
S31 PT Clinical trial 110,564
S30 (MH "Clinical Trials+") 317,874
S29 S23 AND S28 2,390
S28 S24 OR S25 OR S26 OR S27 9,203
S27 TX dyspareunia 1,765
S26 TX dyschezia 68
S25 TX endometrio* 7,681
S24 (MM "Endometriosis") 3,827
S23 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 141,955
S22 TX microsurg* 4,843
S21 TX minimally invasive 30,890
S20 TX remote surg* 286
S19 TX Robot* 16,629
S18 TX keyhole Surg* 76
S17 TX unmanned surg* 2
S16 TX da vinci 910
S15 TX Computer‐Assisted Surg* 3,295
S14 (MH "Robotics") 8,274
S13 TX minilaparoscop* 71
S12 TX microlaparoscop* 30
S11 TX ablation or TX ablative 30,620
S10 (MH "Diathermy") OR (MH "Electrocoagulation") 1,618
S9 TX presacral neurectom* 20
S8 TX LUNA 2,403
S7 TX laser* 34,828
S6 (MM "Lasers") OR (MM "Laser Therapy") 11,141
S5 (MM "Minimally Invasive Procedures") 6,167
S4 TX peritoneoscop* 111
S3 TX celioscop* 2
S2 TX Laparoscop* 36,091
S1 (MM "Laparoscopy") OR (MH "Surgery, Laparoscopic+") 19,821

Appendix 7. Trials registers search strategy

Web platform (clinicaltrials.gov and the WHO portal)

Searched 20 April 2020

Using terms "Endometriosis", "Gynaecological surgery" and "Laparoscopic surgery"

Data and analyses

Comparison 1. Laparoscopic treatment versus diagnostic laparoscopy.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1.1 Overall pain scores unclear measurement instrument (6 months) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.1.1 Excision vs diagnostic laparoscopy 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.2 Overall pain scores unclear measurement instrument (12 months) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.2.1 Excision vs diagnostic laparoscopy 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.3 Quality of life EQ‐5D index summary (6 months) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.3.1 Excision vs diagnostic laparoscopy 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.4 Quality of life SF‐12 mental health component (6 months) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.4.1 Excision vs diagnostic laparoscopy 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.5 Quality of life SF‐12 physical health component (6 months) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.5.1 Excision vs diagnostic laparoscopy 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
1.6 Viable intrauterine pregnancy confirmed by ultrasound 3   Odds Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.6.1 Ablation or excision vs diagnostic laparoscopy 3 528 Odds Ratio (M‐H, Fixed, 95% CI) 1.89 [1.25, 2.86]
1.7 Ectopic pregnancy per pregnancy 1   Odds Ratio (M‐H, Fixed, 95% CI) Totals not selected
1.7.1 Ablation or excision vs diagnostic laparoscopy 1   Odds Ratio (M‐H, Fixed, 95% CI) Totals not selected
1.8 Miscarriage per pregnancy 2   Odds Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.8.1 Ablation or excision vs diagnostic laparoscopy 2 112 Odds Ratio (M‐H, Fixed, 95% CI) 0.94 [0.35, 2.54]
1.9 Adverse events 3   Odds Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.9.1 Ablation or excision vs diagnostic laparoscopy (solid organ injury) 1 39 Odds Ratio (M‐H, Fixed, 95% CI) 3.00 [0.11, 78.27]
1.9.2 Ablation or excision vs diagnostic laparoscopy (blood transfusion) 1 39 Odds Ratio (M‐H, Fixed, 95% CI) 3.00 [0.11, 78.27]
1.9.3 Excision vs diagnostic laparoscopy (vascular injury) 2 487 Odds Ratio (M‐H, Fixed, 95% CI) 0.33 [0.01, 8.05]
1.9.4 Excision vs diagnostic laparoscopy (visceral injury) 2 487 Odds Ratio (M‐H, Fixed, 95% CI) 2.97 [0.12, 73.30]
1.9.5 Excision vs diagnostic laparoscopy (infection) 2 487 Odds Ratio (M‐H, Fixed, 95% CI) 1.68 [0.60, 4.72]
1.9.6 Excision vs diagnostic laparoscopy (conversion to laparotomy) 1 341 Odds Ratio (M‐H, Fixed, 95% CI) Not estimable

Comparison 2. Laparoscopic ablation and uterine nerve transection versus diagnostic laparoscopy.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
2.1 Adverse events 1   Odds Ratio (M‐H, Fixed, 95% CI) Totals not selected
2.1.1 Vascular injury 1   Odds Ratio (M‐H, Fixed, 95% CI) Totals not selected

Comparison 3. Laparoscopic ablation versus laparoscopic excision.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
3.1 Overall pain scores (reduction in VAS at 12 months) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected

Comparison 4. Helium thermal coagulator versus electrodiathermy.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
4.1 Quality of life (9 months) 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
4.1.1 EHP‐30 pain 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
4.1.2 EHP‐30 control and powerlessness 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
4.1.3 EHP‐30 emotional well‐being 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
4.1.4 EHP‐30 social support 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
4.1.5 EHP‐30 self‐image 1   Mean Difference (IV, Fixed, 95% CI) Totals not selected
4.2 Adverse events 1   Odds Ratio (M‐H, Fixed, 95% CI) Totals not selected
4.2.1 Visceral injury 1   Odds Ratio (M‐H, Fixed, 95% CI) Totals not selected

4.1. Analysis.

4.1

Comparison 4: Helium thermal coagulator versus electrodiathermy, Outcome 1: Quality of life (9 months)

4.2. Analysis.

4.2

Comparison 4: Helium thermal coagulator versus electrodiathermy, Outcome 2: Adverse events

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abbott 2004.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single centre; outpatient department of The James Cook University Hospital in Middlesbrough in the UK.
Follow‐up
12 months but only 6 month follow‐up data could be included in the meta‐analysis (all measures were readministered immediately before the second surgery at 6 months, and on follow‐up at 12 months after the first surgery.
Participants Inclusion criteria
Clinical symptoms and signs suggestive of endometriosis, such as dysmenorrhoea, no to presence of menstrual pelvic pain, dyspareunia or dyschezia, and pelvic abnormality on examination, in association with histological evidence of endometriosis at time of surgery.
Indication for intervention: pain.
Severity of disease: rAFS Stage 1–4.
Exclusion criteria
Suspected gynaecological malignancy or its precursors, current or chronic pelvic inflammatory disease, or became pregnant preoperatively.
Number of participants: 39 women randomised: 20 group 1 (immediate surgery group) and 19 group 2 (delayed surgery group).
Interventions Treatment group 1
Laparoscopic excision and histological diagnosis. In this immediate surgery group, women had excision of endometriosis by laparoscopy performed at surgery. Histological diagnosis of endometriosis confirmed.
Treatment group 2
Diagnostic laparoscopy only; laparoscopic excision was performed 6 months later. In this delayed surgery group, women had a staging laparoscopy performed at the time of first surgery, with note made of rAFS score, and a detailed laparoscopic assessment of endometriosis.
Outcomes Primary outcomes
Overall pain: reported by participants completing a VAS prior to surgery and 6 months following surgery (VAS anchored between 0 (labelled no change in pain) and 100 (labelled complete relief of pain)).
Live birth rate: not reported.
Secondary outcomes
Improvement in most troublesome symptom: not reported.
Quality of life: reported by participants completing the EQ‐5D and SF‐12 questionnaire prior to surgery and 6 months following surgery. Before the first surgery, women completed a VAS assessment for dysmenorrhoea, non‐menstrual pelvic pain, dyspareunia and dyschezia.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: reported solid organ and vascular injury and conversion to laparotomy. There were 2 complications in immediate surgery group; 1 woman had disease of the posterior cervix that required a laparotomy to repair, and a second woman had a 2 unit blood transfusion postoperatively for symptomatic surgical anaemia.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation was presented. Sample size calculations based on assumption that there would be a 50% reduction in pain after excision of endometriosis and that a 22% placebo response to surgery would be reported. Based on these factors, 40 women required in the study. Significance set at 5% level. To allow for a 20% rate due to dropout or exclusion for a diagnosis other than endometriosis, 50 women were sought for the study.
Notes Publication: journal article.
Clinical trial registration number: not reported.
Study dates: inclusion of participants between January 1999 and August 2000, follow‐up until 12 months after the first surgery.
Funding: supported by the Academic Department of Gynaecological Surgery, James Cook University Hospital, Teesside, UK.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: computer generated randomisation.
Quote: "Randomization was by computer to generated randomisation blocks in balanced groups of 10."
Allocation concealment (selection bias) Low risk Comment: third party allocation.
Quote: "…concealment achieved by third to party allocation to one of two groups."
Blinding of participants and personnel (performance bias)
All outcomes Low risk Comment: blinding of participants only.
Quote: "Medical and nursing staff not involved with the research team undertook pre‐intervention and postoperative care. The operative notes were kept within the operating suite and could be accessed in case of emergency. Separate notes accompanied the patient to the recovery areas and postoperative care ward. No information was given to staff responsible for postoperative care, to the patient, to the patient's family, or to general practitioners regarding the exact procedure that had been performed. Surgeons and other staff present during the surgical procedure did not interact with the patients postoperatively, to minimize potential influence."
Blinding of outcome assessment (detection bias)
All outcomes Low risk Comment: blinding of outcome assessors and participants.
Quote: see 'Blinding of participants and personnel.'
Incomplete outcome data (attrition bias)
All outcomes Low risk Follow‐up
Entered the study: 29 participants.
Lost to follow‐up: 0 (0%) participants.
Exclusions: none.
Intention to treat analysis
Intention to treat principle was used for all analyses.
Quote: "All analyses were two to tailed and undertaken by intention to treat."
Selective reporting (reporting bias) Unclear risk Published protocol
Comment: protocol was available all outcomes were reported; however, adverse events were not reported.
Other bias Low risk Included participant characteristics
Comment: no evidence of a differences in baseline participant characteristics.
Quote: "There were no significant differences between the groups at baseline for any demographic parameter, pain or quality of life measure, or previous treatment for endometriosis."
Funding source
Not detailed.
Ethical approval
Comment: obtained.
Quote: "Approval for the study was obtained from the institution's ethics committee."
Other sources
No other biases were evident.

Di Donato 2015.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single centre; tertiary care university hospital in Italy.
Follow‐up
3 months.
Participants Inclusion criteria
Women with uterine retroversion who underwent laparoscopic surgery for endometriosis.
Indication for surgery: not stated.
Severity of disease: not stated.
Exclusion criteria
Not stated.
Number of participants: 30 women randomised: 15 in each group.
Interventions Treatment group 1
Laparoscopic surgery for endometriosis with additional uterine suspension.
Treatment group 2
Laparoscopic surgery for endometriosis only.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
Not stated.
Notes Publication: conference abstract.
Clinical trial registration number: not reported.
Study dates: not reported.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Comment: method of sequence generation not stated.
Quote: "Patients were randomised sequentially into two groups: 15 underwent additional laparoscopic uterine suspension using a new technique and 15 underwent only laparoscopic surgery for endometriosis."
Allocation concealment (selection bias) Unclear risk Comment: method of allocation concealment not stated.
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: not reported.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: not reported.
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Follow‐up
Entered the study: 30 participants.
Lost to follow‐up: not reported.
Exclusions: not reported.
Intention to treat analysis
Intention to treat principle not reported.
Selective reporting (reporting bias) Unclear risk Published protocol: no.
Comment: protocol not available.
Other bias Unclear risk Included participant characteristics
Comment: not reported.
Funding source: not reported.
Ethical approval
Comment: not reported.
Other sources
No other biases evident from trial report.

Gad 2012.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Multicentre; Gynaecology Endoscopic Units in El Menoufia University Hospital and Infertility clinic at a private hospital in Egypt.
Follow‐up
18 months of follow‐up or up to 20 weeks of pregnancy.
Participants Inclusion criteria
41 infertile women with laparoscopically confirmed endometriosis, stage I or II of the revised AFS classification.
Indication for intervention: infertility.
Severity of disease: rAFS Stage 1 or 2.
Exclusion criteria
Not stated.
Number of participants: 41 women randomised: 20 in group 1 (laparoscopic ablation or resection) and 21 in group 2 (diagnostic laparoscopy only).
Interventions Treatment group 1
Laparoscopic ablation or resection.
Treatment group 2
Diagnostic laparoscopy only.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Viable pregnancy confirmed by ultrasound: reported. Singleton, twin and higher multiple pregnancies not accounted for.
Ectopic pregnancy: not reported.
Miscarriage: reported but not defined.
By end of study, 19/41 (46.3%) women conceived and no abortion occurred.
Stillbirth: not reported.
Termination of pregnancy: not reported.
Gestational age at birth: not reported.
Birth weight: not reported.
Neonatal mortality: not reported.
Major congenital anomaly: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
No power calculation performed was presented in study report.
Notes Publication: conference abstract.
Clinical trial registration number: not reported.
Study dates: not reported.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Comment: method of sequence generation not stated.
Quote: "Twenty women were randomly allocated to resection or ablation of visible endometriosis during laparoscopy (Group I), and twenty‐one women to diagnostic laparoscopy only (Group II)."
Allocation concealment (selection bias) Unclear risk Comment: method of allocation concealment not stated.
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: did not report blinding of participants.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: did not report blinding of outcome assessors.
Incomplete outcome data (attrition bias)
All outcomes Low risk Follow‐up
Entered the study: 41 participants.
Lost to follow‐up: 0 (0%) participants.
Exclusions: 0 participants.
Intention to treat analysis
Intention to treat principle was not reported.
Selective reporting (reporting bias) Unclear risk Protocol unavailable but outcomes in methods and results were similar. Conference abstract so full description of methods and results not available. Adverse events were not reported.
Other bias Low risk Included participant characteristics
Comment: no statistical differences between intervention and control group participants.
Quote: "The base line distribution of subjects was similar in the two groups."
Funding
Comment: not stated.
Ethical approval
Comment: not stated.
Other sources
No other biases evident from trial report.

Healey 2010.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single centre university teaching hospital in Australia.
Follow‐up
12 months.
Participants Inclusion criteria
Women recruited from an outpatient setting with pain symptoms suggestive of endometriosis (dysmenorrhoea, deep dyspareunia or cyclic pelvic pain) who had been booked for an operative laparoscopy. Recruitment between July 2001 and September 2007. Participants had to provide informed consent, speak English, not be using or planning to use continuous hormonal therapy, and aged > 18 years. At laparoscopy, each recruited participant's pelvis and abdomen were assessed for the presence of visible endometriosis.
Indication for intervention: pain.
Severity of disease: rAFS Stage 1–4.
Exclusion criteria
No obvious endometriosis or there was obvious endometriosis involving the muscle levels of bowel, bladder or ureter.
Number of participants: 178 women randomised: 89 in group 1 (laparoscopic ablation) and 89 in group 2 (laparoscopic excision).
Interventions Treatment group 1
Laparoscopic ablation.
Treatment group 2
Laparoscopic excision.
Treatment of all recognised endometriosis was performed by a trainee gynaecologist while supervised and assisted by the consultant gynaecologist with expertise in the chosen treatment method (ablation or excision).
Outcomes Primary outcomes
Overall pain: reported with participants completing a VAS prior to surgery and 3, 6, 9 and 12 months after surgery.
Null hypothesis was that there was no evidence of a difference in overall pain VAS scores between groups 1 year after operation. A questionnaire assessing pain types and severity was completed by participants before surgery and then every 3 months for 1 year. Pain severity measured using 1–10 cm VAS with 'no pain' at left end and 'worst imaginable pain' at right end. VAS lines measured to the nearest millimetre.
Secondary outcomes
Improvement in most troublesome symptom: not reported.
Quality of life: not reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation presented. Power calculation assumed a base reduction in overall pain VAS score of 3.7; a clinically significant difference between groups being a change of VAS score of 1.0; an SD of 2.0; and a power of 80% and alpha value of 5%. The calculated sample size was 49 in each group. To allow for wastage, a sample size of 120 (60 in each group) was chosen. Because an interim analysis demonstrated a participant loss of 35% at 1 year, the sample size was increased to 180 to compensate.
Notes Publication: journal article.
Clinical trial registration number: not reported.
Study dates: recruitment between July 2001 and September 2007.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: computer random number generator.
Quote: "Randomization of subjects occurred intra to operatively at the time of surgery once endometriosis was diagnosed visually and after evaluation of the pelvis confirmed no involvement of rectal, ureteric, or bladder muscle. Treatment randomisation was performed with use of a computer random number generator."
Allocation concealment (selection bias) Low risk Comment: consecutively numbered opaque envelopes.
Quote: "Treatment randomisation was performed with use of a computer random number generator, and the results were placed in consecutively numbered opaque envelopes."
Blinding of participants and personnel (performance bias)
All outcomes Low risk Comment: blinding of participants only.
Quote: "Both the subjects and the medical staff performing follow to up care were blinded to the type of treatment."
Blinding of outcome assessment (detection bias)
All outcomes Low risk Comment: blinding of outcome assessors.
Quote: see 'Blinding of participants and personnel.'
Incomplete outcome data (attrition bias)
All outcomes High risk Follow‐up
Entered the study: 178 participants.
Lost to follow‐up: 46 (26%) participants.
Exclusions: 29 (16%) participants.
Intention to treat analysis
Comment: intention to treat principle was deployed.
Quote: "The remainder were included as this was an "intention to treat" study (ablation N = 85 and excision N = 85)."
Selective reporting (reporting bias) Unclear risk Comment: protocol unavailable; all outcomes referred to within the methods were reported. Adverse events not reported.
Other bias Low risk Included participant characteristics
Comment: no statistical differences between intervention and control group participants.
Quote: "no evidence of a differences were found when demographic factors and pre‐intervention operation VAS pain scores were compared between subjects included at the 12 to month analysis and those excluded."
Funding
Not stated.
Ethical approval
Comment: obtained.
Quote: "This study was approved by the Research and Ethics Committees of the Royal Women's Hospital, Melbourne."
Other sources
No other biases were evident from the trial report.

Jarrell 2005.

Study characteristics
Methods Design
Parallel randomised controlled trial
Setting
Single centre in Canada
Follow‐up
12 months
Participants Inclusion criteria
Severe pelvic pain requiring investigation, premenopausal state and no evidence of pregnancy. Women entered study at the time of laparoscopy if the clinical impression was that of endometriosis.
Indication for intervention: pain.
Severity of disease: rAFS Stage 1–3.
Exclusion criteria
Severe ancillary medical disease, endometriosis that was too expensive to resect at laparoscopy and symptoms requiring urgent intervention.
Number of participants: 16 women randomised: 9 in group 1 (laparoscopic excision and biopsy) and 7 in group 2 (diagnostic laparoscopy and biopsy).
Interventions Treatment group 1
Laparoscopic excision and biopsy.
Treatment group 2
Diagnostic laparoscopy and biopsy.
Outcomes Primary outcomes
Overall pain: reported. Women completed pain diaries, using VASs daily for 1 month at baseline and then daily for 1 month at 3‐month intervals for the next year.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation presented. Determined the desired sample size in a preliminary pilot study. A meaningful outcome was 50% reduction in pain. With a 65% improvement in the treatment group and a 35% improvement in the control group, required 42 women per group for an alpha of 0.05 and a beta of 0.80. Predicated a potential 20% loss of women, leaving a required total of 100 women (50 per group).
Notes Publication: journal article.
Clinical trial registration number: not reported.
Study dates: not reported.
Funding: project funded by a grant from the Alberta Heritage Foundation for Medical Research.
Conflicts of interest: none declared.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: computer generated randomisation.
Quote: "We used computer generated randomisation to allocate women to the control or excision group. Randomisation in blocks of 5 subjects were stratified for severity based on the presence or absence of previous pelvic surgery for endometriosis."
Allocation concealment (selection bias) Low risk Comment: opaque, sealed envelopes.
Quote: "Cards indicating allocation were kept in opaque envelopes in the operating groom and opened at the time of laparoscopy."
Blinding of participants and personnel (performance bias)
All outcomes Low risk Comment: blinding of participants only.
Quote: "Operating room staff members were aware of the allocation, but all remaining staff were blinded. All patients had 3 incisions, to avoid breaches in the integrity of the trial, and a biopsy of a representative portion of the disease. Women who participated in the trial were transferred back to the care of their referring physician and were seen as required postoperatively. They remained blinded to the identify of their procedure for 1 year, and the referring physician did not have access to the operative record in the clinic chart."
Blinding of outcome assessment (detection bias)
All outcomes Low risk Comment: blinding of outcome assessors.
Quote: see 'blinding of participants and personnel.'
Incomplete outcome data (attrition bias)
All outcomes High risk Follow‐up
Entered the study: 29 participants.
Lost to follow‐up: 15 (52%) participants.
Exclusions: 0 (0%) participants.
Intention to treat analysis
Comment: intention to treat analysis reported within the study.
Selective reporting (reporting bias) Unclear risk Comment: protocol unavailable; all outcomes referred to within the methods were reported. Adverse events were not reported.
Other bias Low risk Included participant characteristics
Comment: no statistical differences between intervention and control group participants.
Quote: "The groups were similar in gravidity, parity, preoperative pain scores, and ASRM [American Society for Reproductive Medicine] scores at surgery."
Source of funding
Comment: source of funding detailed within the report.
Quote: "This project was funded by a grant from the Alberta Heritage Foundation for Medical Research."
Ethical approval
Comment: obtained.
Quote: "The University of Calgary Ethics Committee approved the study."
No other biases were evident from the trial report.

Lalchandani 2005.

Study characteristics
Methods Design
Parallel randomised controlled trial
Setting
Likely multicentre trial in the UK
Follow‐up
All women were given VAS pain scores preoperatively and 3, 6 and 12 months postoperatively.
Participants Inclusion criteria
Women presenting to the gynaecology outpatient clinic with a history of pelvic pain, dysmenorrhoea, dyspareunia and dyschezia suggestive of endometriosis or who had previously been diagnosed as having the disease.
Indication for intervention: pain.
Severity of disease: rAFS Stage 1–2.
Exclusion criteria
Aged < 16 years, pregnant or subfertile.
Number of participants: 35 women randomised: 17 in group 1 (laparoscopic ablation) and 18 in group 2 (diagnostic laparoscopy and GnRH analogue (injectable goserelin) with add‐back therapy (tibolone)).
Interventions Treatment group 1
Laparoscopic ablation (helium thermal coagulator therapy).
Treatment group 2
Diagnostic laparoscopy and GnRH analogue (injectable goserelin) with add‐back therapy (tibolone).
Randomisation performed at time of diagnostic laparoscopy.
Outcomes Primary outcomes
Overall pain: reported, however not mentioned in the result section. Women completed VAS forms.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: EQ‐5D and SF‐12. No outcome data reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed but information to repeat the calculation was not presented. Power studies performed prior to study, and 25 women were required in each group.
Notes Publication: 1 journal article and 1 conference abstract.
Clinical trial registration number: not reported.
Study dates: not reported.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Comment: unclear method of random sequence generation.
Quote: "Randomisation into either HTC [helium thermal coagulator] or GnRH to a therapy was done at the time of diagnostic laparoscopy."
Allocation concealment (selection bias) Unclear risk Comment: method of allocation concealment not stated.
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: did not report blinding of personnel.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: did not report blinding of outcome assessors.
Incomplete outcome data (attrition bias)
All outcomes Low risk Follow‐up
Entered the study: 35 participants.
Lost to follow‐up: 0 (0%) participants.
Exclusions: 0 (0%) participants.
Intention to treat analysis
Comment: intention to treat analysis was not reported within the study.
Selective reporting (reporting bias) Unclear risk Comment: protocol not available. Incomplete data reporting.
Quote: "Analysis of the pain scores and of the success rates of the two treatment modalities will be discussed in our second paper comparing the effectiveness of medical versus surgical treatment." Not published (August 2013). Adverse events were not reported.
Other bias Low risk Included participant characteristics
Comment: no evidence of a differences in participant characteristics.
Funding
Comment: not stated.
Ethical approval
Comment: obtained.
Other sources
No other biases were evident from the trial report.

Marcoux 1997.

Study characteristics
Methods Design
Parallel randomised controlled trial
Setting
Multicentre; 25 hospitals in Canada
Follow‐up
9 months or until 20 weeks of pregnancy
Participants Inclusion criteria
Aged 20–39 years; infertility (≥ 12 consecutive months of unprotected intercourse in unsuccessful attempts to become pregnant); normal ovulatory cycles; partner's semen sample containing ≥ 20 million motile spermatozoa; no previous surgical treatment for endometriosis; no medical treatment for endometriosis in previous 9 months; no ovulatory drug therapy or intrauterine insemination with partner's sperm in previous month; no other medical or surgical treatment for infertility in previous 3 months; no previous oophorectomy or salpingectomy; no history of pelvic inflammatory disease and no severe pelvic pain precluding expectant management.
Indication for intervention: infertility.
Severity of disease: rAFS Stage 1–2.
Exclusion criteria
Women with adhesions precluding adequate visualisation of a tube or ovary; women in whom the laparoscopic tubal patency test revealed complete obstruction of 1 or both tubes, unless hysterosalpingography in the previous year had indicated that both tubes were patent.
Number of participants: 341 women randomised: 172 in group 1 (laparoscopic ablation or excision) and 169 in group 2 (diagnostic laparoscopy only).
Interventions Treatment group 1
Laparoscopic ablation or excision, which involved the destruction or removal of all visible endometriotic implants and the lysis of adhesions. Choice of instruments left to surgeon. Implants destroyed by cautery only (78%), laser only (19%) or a combination (3%).
Treatment group 2
Diagnostic laparoscopic only. Removal of implants and adhesiolysis were not allowed.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Viable intrauterine pregnancy confirmed by ultrasound: defined as "all the women who became pregnant had ultrasonography."
Pregnancy loss:
Ectopic pregnancy: reported but not defined.
Miscarriage: reported but not defined.
Stillbirth: not reported.
Termination of pregnancy: not reported.
Note: 3 fetal losses due to ectopic pregnancies (2 in the laparoscopic to surgery group and 1 in the diagnostic to laparoscopy group).
Gestational age at delivery: not reported.
Birth weight: not reported.
Neonatal mortality: not reported.
Major congenital abnormalities: not reported.
Adverse events: reported but not defined. Notes as intraoperative and postoperative complications.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation presented. 330 women were required to detect a 15% difference in the primary endpoint (alpha 0.05, beta 0.20, 2‐tailed test) if the expected probability in the control group was between 15% and 30%.
Notes Publication: 2 journal article.
Clinical trial registration number: not reported but study was supported by a grant from Medical Research Council of Canada.
Study dates: October 1992 to April 1996.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: method of sequence generation was computer generated random number tables.
Quote: "Stratified randomisation according to hospital, balanced for every two to six assignments. Allocation by telephone call to central randomisation service while the patient was anaesthetised. Women were informed which group they had been randomised to following the surgery and were not blinded during the follow to up period."
Allocation concealment (selection bias) Low risk Comment: method of allocation concealment was by a telephone call to central randomisation service while the participant was anaesthetised.
Quote: "A surgical assistant called the centralized randomisation service while the patient was still anaesthetised."
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: did not report blinding of personnel.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: did not report blinding of outcome assessors.
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Follow‐up
Entered the study: 341 participants.
Lost to follow‐up: 21 (6%) participants.
Exclusions: 28 (8%) participants.
Intention to treat analysis
Comment: intention to treat analysis was not reported within the study.
Selective reporting (reporting bias) Unclear risk Comment: protocol unavailable but outcomes in methods and results were similar. Did not report birth rate.
Other bias Low risk Included participant characteristics
Comment: no statistical differences between intervention and control group participants.
Quote: "The baseline characteristics of the women are shown in Table 1. Twelve women (3.5%) — seven in the laparoscopic to surgery group and five in the diagnostic to laparoscopy group — had a previous diagnosis of endometriosis. Tubal patency was documented during the laparoscopy in 99 % and 98 % of the women in the laparoscopic surgery group and the diagnostic to laparoscopy group, respectively, and by previous hysterosalpingography in the remainder. The proportion of women whose status at the end of the 36 to week follow to up was confirmed by a pregnancy test (67 %) did not differ between the two groups."
Ethical approval
Comment: obtained.
Quote: "The study protocol was approved by the appropriate review committee at each hospital, and all the women gave written consent before the laparoscopy was performed."
Source of funding
Supported by a grant from the Medical Research Council of Canada. Dr Marcoux holds a National Health Research Scholarship from Health Canada.
Other sources
No other biases were evident from the trial report.

Misra 2020.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single endometriosis centre in the UK.
Follow‐up
At 6, 12 and 36 weeks following surgery.
Participants Inclusion criteria
Women aged 16–50 years presenting between January 2014 and September 2017 to a UK gynaecology outpatient clinic with pelvic pain and clinical diagnosis of mild or moderate endometriosis.
Indication for intervention: pelvic pain and a clinical diagnosis of mild or moderate endometriosis.
Severity of the disease: mild or moderate endometriosis.
Exclusion criteria
Women with possibility of a gynaecological cancer, with advanced endometriosis or currently pregnant.
Number of participants: 192 women randomised: 96 in group 1 (electrodiathermy) and 96 in group 2 (helium thermal coagulation).
Interventions Treatment group 1
Electrodiathermy.
Treatment group 2
Comment: helium thermal coagulation.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: EHP‐30.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: reported. Postoperative complications assessed at 6 and 12 weeks.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation was presented. To detect a 12‐week mean difference in VAS scores for cyclical pain of 18 mm with an SD of 40 mm (assuming equal allocation, 80% power and a 5% 2‐tailed significance level), data from a minimum of 79 women in each group were required. Assuming a maximum of 15% loss to follow‐up, ≥ 93% women needed to be recruited to each group. The SD was set at the highest relevant estimate found in the literature, and 18 mm was taken as the minimum important between group difference based on information from this literature.
Notes Publication: journal article.
Clinical trial registration number: ISRCTN 50928834.
Study dates: laparoscopic surgery between January 2014 and September 2017.
Funding: National Institute for Health Research under its Research for Patient Benefit Programme (project number PB‐PG‐0212‐27072).
Conflicts of interest: the authors declare no conflicts of interest.
Corresponding author was not contacted.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: randomisation list.
Quote: "A randomization list, using random permuted blocks of sizes between 2 and 8, was drawn up by an independent statistician and incorporated in a password‐protected database constructed by an information technology specialist who had no other role in the study."
Allocation concealment (selection bias) Low risk Comment: password protected database.
Quote: "A randomization list, using random permuted blocks of sizes between 2 and 8, was drawn up by an independent statistician and incorporated in a password‐protected database constructed by an information technology specialist who had no other role in the study."
Blinding of participants and personnel (performance bias)
All outcomes Low risk Comment: double blind.
Quote: "The study was double‐blinded, whereby participants, assessors and the trial statistician were not aware of the intervention received. Of necessity, the surgeon was not blind to the intervention. Since both groups of patients had laparoscopic treatment, there were no indicators to the patients, nursing staff or other clinicians to suggest which intervention has been performed. Post‐operative management did not indicate to the women the procedure received…"
Blinding of outcome assessment (detection bias)
All outcomes Low risk Comment: blinding of outcome assessor.
Quote: "Participants were invited to attend a dedicated outpatient follow‐up clinic to be assessed by an independent practitioner (research nurse), blind to the procedure the patient had received."
Incomplete outcome data (attrition bias)
All outcomes Low risk Follow‐up: 36 months of follow‐up (primary outcome 12 weeks postoperatively).
Entered the study: 192 participants.
Lost to follow‐up: 37 (19%) participants for the primary outcome point at 12 weeks.
Exclusions before randomisation: 274 (106 in theatre, predominantly because no endometriosis was identified at laparoscopy).
Intention to treat principle: yes.
Quote: "Data analysis was blind to group allocation on an intention‐to‐treat basis."
Selective reporting (reporting bias) Unclear risk Published protocol: no – trial was registered (ISRCTN 50928834).
Other bias Low risk Included participant characteristics:
Comment: similar findings.
Quote: "Baseline characteristics of randomized participants are shown in Table 1; variables were well balanced across the trial arms."
Funding source: National Institute for Health Research under its Research for Patient Benefit Programme (project number PB‐PG‐0212‐27072).
Ethical approval:
Comment: obtained.
Quote: "The study was approved on 3rd October 2013 by the NRES East Midlands – Leicester Ethics Committee (13/EM/0354) and registered in December 2013 (ISRCTN 50928834)."
Other sources:
No other biases were evident from the trial report.

Moini 2012.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single centre; Gynaecological Outpatient Clinic of Arash Hospital, Tehran between April 2008 and March 2009.
Follow‐up
9 months.
Participants Inclusion criteria
Aged 20–32 years, unexplained infertility > 1 year, normal semen analysis, normal ovulatory cycles (menstrual interval 24–35 days and biphasic basal temperature), normal hormonal assay (thyroid stimulating hormone, follicle stimulating hormone, prolactin) and normal hysterosalpingography.
Indication for intervention: infertility.
Severity of disease: rAFS score 1 or 2.
Exclusion criteria
Surgical history for infertility or endometriosis, oophorectomy, salpingectomy, history of pelvic inflammatory disease and who received any treatment for endometriosis during the previous 3 months.
Number of participants: 146 women randomised: 73 in each group.
Interventions Treatment group 1
Laparoscopic ablation or excision. Women underwent ablation to remove any visible endometrial implants. During surgery, surgeon chose type of procedure. Removal was by bipolar cauterisation. In difficult anatomical positions, implants were cauterised with the fulguration method without complete resection.
Treatment group 2
Diagnostic laparoscopy only.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Viable intrauterine pregnancy confirmed by ultrasound: reported. Visualisation at ultrasound of an embryo with cardiac activity at 6–7 weeks of pregnancy.
Pregnancy loss:
Ectopic pregnancy: not reported.
Miscarriage: not reported.
Stillbirth: not reported.
Termination of pregnancy: not reported.
Gestational age at delivery: not reported.
Birth weight: not reported.
Neonatal mortality: not reported.
Major congenital abnormalities: not reported.
Adverse events:reported but not comprehensively defined. No adverse events reported. Complications during or postsurgery, such as: intestinal injury, slight tear of the tubal serosa, vascular trauma, infection of wounds, haematomas and urinary tract infection.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation was presented. Authors estimated the rate of pregnancy in the surgical group as 15% and the diagnostic group, 35%. Calculated that 73 women would be required in each group to detect differences in pregnancy rate with a power of 90% and alpha 0.05 by Epi Info (www.cdc.gov/epiinfo/).
Notes Publication: journal article and trial registration.
Clinical trial registration number: IRCT201012311952N2.
Study dates: April 2008 to March 2009.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Comment: method not stated.
Quote: "After confirmation of minimal or mild endometriosis by diagnostic laparoscopy in all patients, eligible women were randomly assigned to surgery or diagnostic laparoscopy only."
Allocation concealment (selection bias) Low risk Comment: consecutively numbered, opaque sealed envelopes.
Quote: "After confirmation of minimal or mild endometriosis by diagnostic laparoscopy in all patients, eligible women were randomly assigned to surgery or diagnostic laparoscopy only using consecutively numbered, opaque sealed envelopes by a surgical assistant while the patient was still anaesthetised."
Blinding of participants and personnel (performance bias)
All outcomes Low risk Comment: blinding of participants only.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: did not report blinding of outcome assessors.
Incomplete outcome data (attrition bias)
All outcomes High risk Follow‐up
Entered the study: 146 participants.
Lost to follow‐up: 24 (16%) participants.
Exclusions: 36 (24%) participants.
Intention to treat analysis
Comment: intention to treat analysis was not reported within the study.
Selective reporting (reporting bias) Unclear risk Comment: protocol was available and outcomes were reported. Did not report live birth rate.
Other bias Low risk Included participant characteristics
Comment: no statistical differences between intervention and control group participants.
Quote: "Age, body mass index (BMI) and duration of infertility were statistically similar in both groups (p>0.05)."
Ethical approval
Comment: obtained.
Quote: "The Ethics Institutional Review Board of Tehran University of Medical Sciences approved the study and informed consent was obtained from all participants after counselling regarding the potential risks of laparoscopy."
Source of funding
Comment: source of funding stated.
Quote: "This study was supported by a grant aid from Tehran University of Medical Sciences."
Other sources
Comment: no other biases were evident from the trial report.

Roman 2018.

Study characteristics
Methods Design
Parallel randomised controlled trial. Unblinded, 1:1 parallel‐groups, controlled randomised study to assess the hypothetical superiority of conservative rectal surgery over segmental resection in the management of deep endometriosis infiltrating the rectum.
Setting
Multicentre; 3 French referral centres (i.e. Rouen University Hospital, Tenon University Hospital and Lille University Hospital) in France.
Follow‐up
6, 12, 18 and 24 months after surgery.
Participants Inclusion criteria
Aged 18–45 years, managed for deep endometriosis infiltrating the rectum up to 15 cm from the anus, measuring > 20 mm in length, involving at least the muscular layer in depth and up to 50% of rectal circumference.
Indication for intervention: not stated.
Severity of disease: rAFS stage 3 and 4 (rAFS points range 19–98).
Exclusion criteria
Not stated.
Number of participants: 60 women randomised: 27 in group 1 (conservative surgery group) and 33 in group 2 (radical surgery group).
Interventions Treatment group 1
Conservative surgery group involving surgical management of rectal endometriosis by either rectal shaving or disc excision.
Treatment group 2
Radical surgery group involving segmental colorectal resection, which could be associated with additional procedures on the left, transverse or right colon, caecum or small bowel, when required.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: participants completed baseline questionnaires including questions about pelvic complaints related to endometriosis using VAS, bowel movements and bladder voiding, the Knowles–Eccersley–Scott‐Symptom Questionnaire, GIQLI, the Wexner scale, the Urinary Symptom Profile and the SF‐36.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: reported and classified using the Clavien‐Dindo Classification.
Presented in Table 2 of the publication.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation was presented. The percentage of participants presenting with main outcomes was expected to average 10% in group 1 versus 50% in group 2. Hence, 60 participants were randomised to reach the principal aim with a power of at least 80% and admitting an alpha error of 5% when using Fisher's exact test and accounting for participants who did not receive the allocated treatment.
Notes Publication: journal article.
Clinical trial registration number: ClinicalTrials.gov – NCT01291576.
Study dates: recruitment from March 2011 to August 2013; surgery from March 2011 to October 2013; 12 months of follow‐up in original paper; extended follow‐up until 5 years.
Funding: supported by a grant from the clinical research programme for hospitals (PHRC) in France.
Conflicts of interest: authors declared no competing interests.
Corresponding author was not contacted.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: randomisation lists for each centre.
Quote: "Assignment of a patient to conservative surgery or colorectal resection was based on randomization lists drawn up separately for each centre by a statistician with no clinical involvement in the trial (M.B.). The details, like the block size, were not revealed to investigators before the end of the study."
Allocation concealment (selection bias) Low risk Comment: consecutively numbered, opaque sealed envelopes.
Quote: "the investigator of each centre received 60 sequentially numbered, opaque, sealed envelopes, which were opened only after the patient had completed all baseline assessments and had given written consent to be enroled in the trial."
Blinding of participants and personnel (performance bias)
All outcomes High risk Comment: no blinding.
Quote: "We conducted an unblinded, 1:1 parallel‐arms, controlled randomized study to assess the hypothetical superiority of conservative rectal surgery over segmental resection in the management of deep endometriosis infiltrating the rectum (ENDORE, NCT 01291576)."
Blinding of outcome assessment (detection bias)
All outcomes High risk Comment: no blinding.
Quote: "We conducted an unblinded, 1:1 parallel‐arms, controlled randomized study to assess the hypothetical superiority of conservative rectal surgery over segmental resection in the management of deep endometriosis infiltrating the rectum (ENDORE, NCT 01291576)."
Incomplete outcome data (attrition bias)
All outcomes Low risk Follow‐up
Entered the study: 60 participants.
Lost to follow‐up: 0 (0%) participants.
Exclusions: none.
Intention to treat principle: yes.
Quote: "In accordance with the intention‐to‐treat principle, all randomized patients were included in the analysis."
Selective reporting (reporting bias) Unclear risk Published protocol: no – registration at clinicaltrials.gov.
Comment: protocol unavailable, all outcomes referred to within the methods were reported.
Intervention related adverse events were reported (i.e. complications).
Other bias Low risk Included participant characteristics:
Comment: similar findings for both groups.
Quote: "Table 1 presents the baseline characteristics for each group related to primary and secondary endpoints."
Funding source:
Comment: stated.
Quote: "This work was supported by a grant from the clinical research programme for hospitals (PHRC) in France."
Ethical approval:
Comment: obtained.
Quote: "This study was approved by the local Internal Review Board."
Other sources:
Comment: no other biases were evident from the trial report.

Sutton 1994.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single centre, UK.
Follow‐up
6 months, after which randomisation code was broken.
Participants Inclusion criteria
Not pregnant or lactating, aged 18–45 years, and had not received any treatment (medical or surgical) for endometriosis in the previous 6 months.
Indication for intervention: pain.
Severity of disease: rAFS score 1–3.
Exclusion criteria
Not stated.
Number of participants: 74 women entered study; 63 completed study: 32 in group 1 (laser group) and 31 in group 2 (diagnostic laparoscopy only).
Interventions Treatment group 1
Laparoscopic ablation (laser) and uterine nerve transection; included vaporisation of all visible endometriosis implants, adhesiolysis and uterine nerve transection with the CO2 laser
Treatment group 2
Diagnostic laparoscopy only
Outcomes Primary outcomes
Overall pain: not reported.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
No reference to a power calculation
Notes Publication: journal article.
Clinical trial registration number: not reported.
Study dates: March 1990 to February 1993.
Funding: supported by Birthright Research Grant (Ref:S3/90).
Conflicts of interest: not reported.
Corresponding author was not contacted.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: computer generated randomisation.
Quote: "At the time of laparoscopy, treatment was allocated randomly (computer to generated randomisation sequence)…"
Allocation concealment (selection bias) Unclear risk Comment: method of allocation concealment not stated.
Blinding of participants and personnel (performance bias)
All outcomes Low risk Comment: blinding of participants only.
Quote: "Patients were not informed of which treatment they had been allocated to…"
Blinding of outcome assessment (detection bias)
All outcomes Low risk Comment: blinding of outcome assessors.
Quote: "…an independent observer (research nurse) who was unaware of the treatment that they had been allocated to…"
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Follow‐up
Entered the study: 74 participants.
Lost to follow‐up: 3 (4%) participants.
Exclusions: 11 (15%) participants.
Intention to treat analysis
Comment: intention to treat analysis was not reported within the study.
Selective reporting (reporting bias) Unclear risk Comment: protocol unavailable and outcomes were reported. Outcomes outlined in the methods were reported in the results section. Adverse events were not reported.
Other bias Low risk Included participant characteristics
Comment: no statistical differences between intervention and control group participants.
Quote: "The patient characteristics in both groups were not significantly different."
Ethical approval
Comment: obtained.
Source of funding
Comment: supported by Birthright Research Grant, RCOG and Laserscope, Cwmbran, UK.
Other sources
Comment: no other biases were evident from the trial report.

Tutunaru 2006.

Study characteristics
Methods Design
Prospective, single blind, randomised controlled trial.
Setting
Not stated.
Follow‐up
12 months.
Participants Inclusion criteria
Women of reproductive age, with endometriotic implants discovered by laparoscopy done because of dysmenorrhoea, who had signed informed consent.
Indication for intervention: pain.
Severity of disease: rAFS stage 1.
Exclusion criteria
Severe adhesions, prior abdominal surgery, unwilling to comply with the study.
Number of participants: 69 women randomised: 41 in group 1 (laparoscopic excision or ablation) and 28 in group 2 (diagnostic laparoscopy).
Interventions Treatment group 1
Laparoscopic excision or ablation.
Treatment group 2
Diagnostic laparoscopy.
Outcomes Primary outcomes
Overall pain: collected prior to surgery and 6 and 12 months following surgery. Reporting of results unclear. Core questionnaire with 30 items and 5 pain scales: pain, control and powerlessness, emotional well to being, social support, self to image.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
Power calculation was not presented in the report.
Notes Publication: conference abstract.
Clinical trial registration number: not reported.
Study dates: not reported.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Comment: method not stated.
Quote: "…69 patients were randomly divided in two groups…"
Allocation concealment (selection bias) Unclear risk Comment: no reference to allocation concealment.
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: did not report the blinding of participants.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: did not report blinding of outcome assessors.
Incomplete outcome data (attrition bias)
All outcomes Unclear risk Follow‐up
Entered the study: 69 participants.
Lost to follow‐up: not reported.
Exclusions: not reported.
Intention to treat analysis
Comment: intention to treat analysis was not reported within the study.
Selective reporting (reporting bias) Unclear risk Comment: protocol unavailable and outcomes in the methods were reported. Conference abstract so full description of methods and results not available. Adverse events were not reported.
Other bias Low risk Included participant characteristics
Comment: not stated.
Ethical approval
Comment: not stated.
Source of funding
Comment: not stated.
Other sources
Conference abstract so full description of methods and results not available.
No other biases were evident from the trial report.

Wright 2005.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single centre; district general hospital with a specialist pelvic pain clinic in the UK.
Follow‐up
6 months.
Participants Inclusion criteria
Women with a presumptive diagnosis of endometriosis with a history of dysmenorrhoea, pelvic pain, backache, dyspareunia or dyschezia in the absence of any physical signs such as ovarian cysts or uterosacral nodularity that would point to a diagnosis of more advanced disease.
Indication for intervention: pain.
Severity of disease: rAFS 1.
Exclusion criteria
Women with infiltrating and nodular disease.
Number of participants: 24 women randomised: 12 in each group.
Interventions Treatment group 1
Laparoscopic ablation where endometriosis was ablated using monopolar diathermy at a coagulation current of 50 watts. The closed end of a pair of 3 mm monopolar laparoscopic scissors was used. Coagulation continued until the peritoneum was destroyed and a scar could be seen. All visible lesions were coagulated.
Treatment group 2
Laparoscopic excision was carried out using 3 to mm monopolar diathermy scissors with a combination of 90 watts pure cut and 50 watts coagulation; the majority of the surgery was performed in cutting mode.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: not reported.
Participant satisfaction with treatment: not reported.
Power
Power calculation was described within the report.
Notes Publication: journal article.
Clinical trial registration number: not reported.
Study dates: not reported.
Funding: not reported.
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Unclear risk Comment: unclear method of sequence allocation.
Quote: "A routine laparoscopy was performed; if endometriosis was diagnosed and staged as "mild" (stage 1 to 2 on the revised AFS scale), they were randomised by means of opening a consecutively numbered envelope to receive either ablation or excision of all the identified lesions. Randomization was in blocks of 10 to ensure an equal number in each group."
Allocation concealment (selection bias) Low risk Comment: consecutively numbered envelope.
Quote: "Opening a consecutively numbered envelope to receive either ablation or excision of all the identified lesions."
Blinding of participants and personnel (performance bias)
All outcomes Unclear risk Comment: did not report the blinding of personnel.
Blinding of outcome assessment (detection bias)
All outcomes Unclear risk Comment: did not report the blinding of outcome assessors.
Incomplete outcome data (attrition bias)
All outcomes Low risk Follow‐up
Entered the study: 24 participants.
Lost to follow‐up: 0 (0%) participants.
Exclusions: 0 participants.
Intention to treat analysis
Comment: intention to treat analysis was not reported within the study.
Selective reporting (reporting bias) Unclear risk Comment: protocol unavailable all outcomes referred to within the methods were reported. Adverse events were not reported.
Other bias Unclear risk Included participant characteristics
Comment: not reported.
Ethical approval
Comment: obtained.
Quote: "After agreement by the local research ethics committee."
Source of funding
Comment: not reported.
Other sources
No other biases were evident from the trial report.

Zullo 2003.

Study characteristics
Methods Design
Parallel randomised controlled trial.
Setting
Single centre in Italy.
Follow‐up
6 and 12 months.
Participants Inclusion criteria
Sexually active women of fertile age with severe dysmenorrhoea that persisted for > 6 months and that was unresponsive to medical treatment (i.e. non‐steroidal anti‐inflammatory drugs and oral contraceptives) and a clinical or ultrasonographic (or both) diagnosis of endometriosis.
Indication for intervention: dysmenorrhoea.
Severity of the disease: rAFS stage 1–4.
Exclusion criteria
Women without a midline component of the dysmenorrhoea; pregnancy or breast‐feeding; use of an intrauterine device; major medical diseases; psychiatric disorders; neurological alterations of lumbar‐sacral tract; previous pelvic surgery; history of severe abdominal or pelvic infections; presence of other gynaecological diseases that were demonstrated during laparoscopy; BMI > 30 kg/m2; unable to complete the daily diary; history of alcohol abuse or other drug use.
Number of participants: 126 women randomised: 63 in group 1 (conservative intervention for endometriosis) and 63 in group 2 (conservative intervention for endometriosis associated with presacral neurectomy).
Interventions Treatment group 1
Conservative intervention for endometriosis.
Treatment group 2
Conservative intervention for endometriosis associated with presacral neurectomy.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: not reported.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: reported. No difference in surgical complications between groups. 1 case of significant bleeding from the middle sacral vein in group 2, which was treated successfully by bipolar electrocauterisation during laparoscopy.
Participant satisfaction with treatment: not reported.
Power
Power calculation performed and information to repeat the calculation was presented. Primary endpoint was cure rate. On the basis of the assumption that the cure rate (relief of dysmenorrhea) was 50% in the control group (laparoscopic conservative treatment for endometriosis only), authors needed to enrol 58 participants for each group to demonstrate a difference of 25% between control and experimental groups (laparoscopic treatment for endometriosis plus presacral neurectomy) and to define statistical significance between the groups with an alpha of 0.05 and a beta of 0.20.
Notes Publication: journal article.
Clinical trial registration number: not reported.
Study dates: September 1998 to October 2001.
Funding: not reported.
Conflicts of interest: not reported.
Corresponding author was not contacted.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Comment: randomisation list.
Quote: "With the use of a computer‐generated randomization list, 141 eligible subjects were allocated in single blocks in one of two groups of surgical treatment (groups A and B)."
Allocation concealment (selection bias) Unclear risk Comment: not reported.
Blinding of participants and personnel (performance bias)
All outcomes Low risk Comment: blinding of participants only, no blinding of the surgeons.
Quote: "For the whole duration of the study, each patient was blinded with regard to the surgical treatment that would be performed."
Blinding of outcome assessment (detection bias)
All outcomes Low risk Comment: blinding of outcome assessors.
Quote: "Follow‐up evaluations were performed by the same investigator who was blinded with regard to patient allocation to the respective study groups."
Incomplete outcome data (attrition bias)
All outcomes Low risk Follow‐up
Entered the study: 141 participants.
Lost to follow‐up: 3 (2%) participants.
Exclusions: 12 (9%) participants.
Intention to treat principle: not reported.
Quote: "Six patients in each group were excluded after laparoscopy caused by the presence of other associated gynecologic diseases (four and three women in groups A and B, respectively) and because the clinical and ultrasonographic suspect of endometriosis was not confirmed (two and three women in groups A and B, respectively). Three patients (one and two in groups A and B, respectively) dropped from the study because they did not undergo postoperative subjective evaluation of dysmenorrhea (our primary end point)."
Selective reporting (reporting bias) Unclear risk Comment: protocol unavailable, all outcomes referred to within the methods were reported.
Other bias Low risk Included participant characteristics
Comment: no statistical differences between groups.
Quote: "No significant difference was detected between the two groups in age, parity, and BMI at the entry of the study."
Funding source: not reported
Ethical approval:
Comment: reported.
Quote: "The protocol was approved by the Institutional Review Board of the University of Catanzaro."
Other sources:
No other biases were evident from the trial report.

AFS: American Fertility Society; BMI: body mass index; EHP‐30: 30‐item Endometriosis Health Profile; EQ‐5D: EuroQol‐5D; GIQLI: Gastrointestinal Quality of Life Index; GnRH: gonadotrophin‐releasing hormone; rAFS: revised American Fertility Society; SD: standard deviation; SF‐12: 12‐item Short Form; SF‐36: 36‐item Short Form; VAS: visual analogue scale.

Characteristics of excluded studies [ordered by study ID]

Study Reason for exclusion
Algergawy 2016 Comment: inclusion of women with no definitive diagnosis of endometriosis.
Quote: "…were randomized according to their will into two groups: group I, 205 patients who were treated by controlled ovarian stimulation and IUI [intrauterine insemination] up to 3 trials, if failed ICSI [intracytoplasmic sperm injection] was performed. Group II included 218 patients managed with laparoscopy with aim of diagnosis and treatment."
Alkatout 2013 Comment: wrong comparator.
Quote: "Group 1 (n=125) underwent diagnostic laparoscopy followed by hormone therapy with 3.75mg leuprorelin acetate depot injected subcutaneously monthly for 3 months. Group 2 (n=137) underwent surgical laparoscopy without any subsequent medical treatment. Group 3 (n=148) underwent surgical laparoscopy followed by the same hormone therapy as group 1 over the same period."
Benton 2017 Comment: assessed medical adjuvant preoperatively + inclusion of women with no definitive diagnosis of endometriosis.
Quote: "One‐hundred‐nine gynecologic patients undergoing laparoscopy between June 2015 and January 2016. Intervention: patients received pre‐operative gabapentin (300 mg) or placebo…"
Darai 2010 Comment: compared a laparoscopic approach with an open procedure.
Quote: "Randomized trial of laparoscopically assisted versus open colorectal resection for endometriosis."
Dehbashi 2019 Comment: no randomisation per participant.
Quote: "A table of random numbers was used to choose which ovary to suspend. The entire study population received standard general anesthesia. In the laparoscopic examination of cases with severe endometriosis, both ovaries were routinely suspended to the anterior abdominal wall with PROLENE suture. At the end of the surgery, one of the ovaries was kept suspended for 7 days, whereas the other ovarian suspension suture was cut."
Di Donato 2013 Comment: wrong outcome: assessed adhesion formation.
Quote: "Our study aims to evaluate the role of ovaropexy on reducing ovarian adhesions formation."
Gallicchio 2015 Comment: inclusion of women with no definitive diagnosis of endometriosis.
Quote: "Adult women of reproductive age (18–45 years of age) undergoing clinically indicated diagnostic laparoscopy for pelvic pain, suspected endometriosis, or infertility were eligible…" "Table 1: number of resected lesions in part of the patients = 0."
Kraemer 2019 Comment: wrong outcome: assessed adhesion formation.
Quote: "The work presented here is a randomized controlled clinical study which was performed to compare the eradication rate and adhesion formation of HybridAPC treatment with standard surgical resection."
Lang 2018 Comment: medical adjuvant used.
Quote: "The study enrolled women aged 18–45 years with a diagnosis of endometriosis confirmed by laparoscopy or laparotomy within 10 years before study entry." "Eligible women with endometriosis were randomized using an interactive voice response system at study sites in 1:1 ratio to receive double‐blinded treatment with once‐daily oral dienogest 2 mg or placebo for 24 weeks."
NCT03352076 Comment: assessed medical adjuvant.
Quote: "A comparative, open‐label, randomized, parallel group study to determine Intraperitoneal fluids, tissue, and serum concentrations of VML‐0501 following five days of daily vaginal applications of single dose of VML‐0501 (100 mg Danazol), in comparison to five days of Danazol treatment administered as an oral capsule (Danatrol) at a daily dose of 600 mg."
Orazov 2019 Comment: assessed medical adjuvant.
Quote: "I group included patients (n = 34) only with surgical treatment, group II (n = 35) – patients with combined therapy (surgical treatment + hormone therapy)."
Parazzini 1999 Comment: medical adjuvant used.
Quote: "The protocol allowed after surgery the use of a medical treatment (tryptorelin 3.75 mg slow release every 28 days for 3 months) according to the physician's judgement."
Riley 2019 Comment: compared 2 robot‐assisted laparoscopic approaches.
Quote: "Excision or ablation of superficial endometriosis at the time of robot‐assisted laparoscopy."
Ruan 2015 Comment: compared a laparoscopic approach with an open procedure.
Quote: "The subjects were randomly divided into a control group and a study group with 50 cases in each group. The control group underwent the traditional surgery, while the research group underwent laparoscopy."
Scioscia 2017 Comment: assessed perioperative care.
Quote: "We randomly assigned 227 patients with preoperative evidence of bowel endometriosis to a fast‐track protocol(no preoperative bowel preparation, early restoration of diet, no postoperative antibiotics, and early postoperative mobilization) or conventional care for laparoscopic intestinal surgery."
Soto 2017 Comment: inclusion of women with no definitive diagnosis of endometriosis.
Quote: "Inclusion criteria: Women were included if they were age ≥18 years and were undergoing laparoscopic treatment of pain or infertility with presumed endometriosis as determined by the operating surgeons and/or ultrasound findings of endometrioma(s)." "Table 2: no laparoscopically proven endometriosis in 21/73 (28.8%) of the patients and no histologically proven endometriosis in 31/71 (42.5%) of the patients."
Soysal 2001 Comment: no definitive diagnosis of endometriosis or presenting symptom of pain.
Quote: "Patients with known or suspected endometriosis causing pelvic pain and/or mass with no interest in further childbearing were considered eligible for entrance to the study."
Yang 2019 Comment: assessed a medical adjuvant (subcutaneous injection of gonadotropin‐releasing hormone agonist).
Quote: "Patients in the control group were treated by laparoscopic only, while patients in the observation group were added by the subcutaneous injection of GnRH‐a [gonadotropin‐releasing hormone agonist], based on the treatment of the control group."
Yin 2016 Comment: assessed a medical adjuvant.
Quote: "98 patients were divided into observation group and reference group by random number table, each group included 49 cases, the observation group was treated with laparoscopy in combination with Chinese medicine, and the reference group was treated with laparoscopy combined with gestrinone."
Zhao 2016 Comment: assessed a medical adjuvant.
Quote: "A total of 124 endometriosis‐induced infertile cases of pathological stage I–II were treated by laparoscopic conservative therapy,then they were randomly divided into observation group and control group; 78 cases in observation group were treated by laparoscopic conservative therapy combined with oral administration of Dingkundan, 46 cases in control group were treated by laparoscopic conservative therapy combined with adjunctive therapy using GnRHa."

Characteristics of studies awaiting classification [ordered by study ID]

NCT02282943.

Methods Randomised controlled trial.
Participants Women with endometriosis grade I–III by revised American Fertility Society Scoring.
Interventions Carbon dioxide‐laser compared with Harmonic scalpel.
Outcomes
  1. Visual analogue pain score change at 6 months compared to preoperative baseline.

  2. Quality of life survey (Endometriosis Health Profile Questionnaire).

  3. Hospital Anxiety & Depression Scale.

Notes Full trial report remains unpublished. Discrepancies between the prospective trial registry record and details presented in a thesis, conference abstract and included in a meta‐analysis. Contacted authors seeking clarification.

Characteristics of ongoing studies [ordered by study ID]

Hardcastle 2015.

Study name A randomised, single‐blind clinical trial to investigate the effectiveness of bipolar versus monopolar diathermy treatment on pain symptoms for women with newly diagnosed superficial endometriosis: The Set Study (Superficial Endometriosis Treatment).
Methods Design
Single blind, parallel randomised controlled trial.
Setting
Single centre; UK endometriosis centre in UK.
Follow‐up
8 months (no data could be included in the meta‐analysis since results are awaiting)
Participants Inclusion criteria
Women aged ≥ 18 years with clinical suspicion of endometriosis, found to have superficial endometriosis on diagnostic laparoscopy defined by Stage I or II of the revised American Fertility Society score; willing and able to give informed consent for participation in the study.
Indication for intervention: clinical suspicion of endometriosis with superficial endometriosis on diagnostic laparoscopy.
Severity of disease: superficial endometriosis.
Exclusion criteria
Previous diagnosis of endometriosis from previous surgery/assessment; language or competency barriers exist during consenting; position of endometriosis contraindicates use of either diathermy treatment due to risk of complications (e.g. endometriosis vesicle over the ureter).
Number of participants: not reported (target number of participants: 32).
Interventions Treatment group 1
Monopolar diathermy.
Treatment group 2
Bipolar diathermy.
Outcomes Primary outcomes
Overall pain: visual analogue scale difference in chronic pelvic pain symptoms at 4 and 8 months postoperatively.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not collected
Quality of life: Health State Questionnaire at 4 and 8 months postsurgery.
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: type, frequency and severity of adverse events, including surgical complications.
Participant satisfaction with treatment: not collected.
Power
Not stated
Starting date February 2014
Contact information Rebecca Hardcastle: drrjh@hotmail.co.uk; GynaeResearchTeam@porthosp.nhs.uk
Notes Publication: conference abstract + trial registration website.
Clinical trial registration number: ISRCTN37028168 (retrospectively registered).
Study dates: February 2014 to August 2015.
Funding: Portsmouth Hospital NHS Trust (UK).
Conflicts of interest: not reported.
Contacted corresponding author for clarification of data but no response received.

Mabrouk 2018.

Study name Robot‐assisted versus standard laparoscopic approach for the surgical treatment of deep infiltrating endometriosis.
Methods Design
Parallel randomised controlled trial.
Setting
Single centre; Gynecology and Physiopathology of Human Reproductive Unit, University of Bologna, S. Orsola‐Malpighi Hospital in Italy.
Follow‐up
3 months.
Participants Inclusion criteria
Diagnosis of deep endometriosis based on clinical and transvaginal/transabdominal ultrasound examinations and, when necessary, magnetic resonance; indication for removal of endometriotic lesions by standard and robot‐assisted laparoscopy; obtained informed consent.
Indication for intervention: not reported.
Severity of disease: deep endometriosis.
Exclusion criteria
Contraindications for removal of endometriotic lesions by standard and robot‐assisted laparoscopy; cardiovascular problems; hepatic insufficiency; psychiatric diseases; history of oncological disease.
Number of participants: estimated enrolment: 60 women.
Interventions Treatment group 1
Standard laparoscopic surgery.
Treatment group 2
Robot‐assisted surgery.
Outcomes Primary outcomes
Overall pain: not reported.
Live birth rate: not reported.
Secondary outcomes
Improvement in the most troublesome symptom: not reported.
Quality of life: evaluation of sexual function (Female Sexual Function Index), evaluation of urinary symptoms (Knowles–Eccersley–Scott‐Symptom Scale) and evaluation of bowel symptoms (Bristol Female Lower Urinary Tract Symptoms).
Fertility outcomes: viable intrauterine pregnancy confirmed by ultrasound; pregnancy loss including ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy; time to pregnancy leading to live birth; gestational age at delivery; birth weight; neonatal mortality and major congenital abnormalities: not reported.
Adverse events: complication rate intraoperative and up to 3 months after surgery.
Participant satisfaction with treatment: not reported.
Power
Not stated.
Starting date 20 October 2017
Contact information Diego Raimondo: die.raimondo@gmail.com
Notes Publication: study registered at ClinicalTrials.gov.
Clinical trial registration number: ClinicalTrials.gov – NCT03633786 (first received 16 August 2018).
Study dates: actual study start date: 20 October 2017; estimated primary completion date: October 2019; estimated study completion date: November 2019
Funding: not reported.
Conflicts of interest: the authors declared no competing interests.
Corresponding author was not contacted.

Differences between protocol and review

Implementation of the core outcome set for endometriosis: a minimum data set, known as a core outcome set, has been recently developed using formal consensus methods involving 116 healthcare professionals, 32 researchers, and 206 women with endometriosis from 29 countries (Duffy 2020a). Over 80 speciality journals, including the Cochrane Gynaecology and Fertility Group, have committed to supporting the implementation of the core outcome set for endometriosis. Consensus definitions have been developed for fertility outcomes and will be implemented in this review. Standardised measurement instruments for pain and other symptoms are currently in developed and will be included in the next update of the review.

Outcomes in the previous review of 2014 were:

Primary outcomes:

1. overall pain

2. live birth

Secondary outcomes:

1. Specific types of pain: 1.1 pelvic pain; 1.2 dysmenorrhoea; 1.3 dyspareunia; 1.4 dyschezia.
2. Clinical pregnancy.
3. Miscarriage.
4. Adverse events: 4.1 mortality; 4.2 vascular injury (major and abdominal wall vessels); 4.3 visceral injury (bladder including ureters or bowel injury); 4.4 solid organ injury (uterus); 4.5 conversion to laparotomy; 4.6 infection (intra‐abdominal, urinary, wound); 4.7 venous thromboembolism.

Contributions of authors

Study concept and design: JMD.

Acquisition of data: CB and YB.

Analysis and interpretation of data: CB, YB, CT, JB and JMD.

Drafting of the manuscript CB, YB and JMD.

Critical revision of the manuscript for important intellectual content CT and JB.

Obtaining funding: JMD.

Study supervision JB and JMD.

Sources of support

Internal sources

  • None, Other

External sources

  • National Institute of Health Research, UK

    Cochrane Review incentive scheme

  • Cochrane Review Support Programme, UK

Declarations of interest

CB: none.

YB: none.

CT: does not report a conflict of interest for the current work considered for publication. She discloses the following non‐related but possibly relevant financial activities outside the submitted work (payments to institution, no personal revenue): consultancy (Merck SA, Gedeon Richter, Nordic Pharma), grants for a research fellowship (Merck SA) and travel/accommodations/meeting expenses (Ferring Pharmaceuticals, Gedeon Richter, MSD).

JB: none.

JMD: none.

New search for studies and content updated (conclusions changed)

References

References to studies included in this review

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