When to Do Surgery and When Not to Do Surgery for Endometriosis: A Systematic Review and Meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis with the aim to answer whether operative laparoscopy is an effective treatment in a woman with demonstrated endometriosis compared with alternative treatments. Moreover, we aimed to assess the risks of operative laparoscopy compared with those of alternatives. In addition, we aimed to systematically review the literature on the impact of patient preference on decision making around surgery. DATA SOURCES: We searched MEDLINE, Embase, PsycINFO, ClinicalTrials.gov, CINAHL, Scopus, OpenGrey, and Web of Science from inception through May 2019. In addition, a manual search of reference lists of relevant studies was conducted. METHODS OF STUDY SELECTION: Published and unpublished randomized controlled trials (RCTs) in any language describing a comparison between surgery and any other intervention were included, with particular reference to timing and its impact on pain and fertility. Studies reporting on keywords including, but not limited to, endometriosis, laparoscopy, pelvic pain, and infertility were included. In the anticipated absence of RCTs on patient preference, all original research on this topic was considered eligible. TABULATION, INTEGRATION, AND RESULTS: In total, 1990 studies were reviewed. Twelve studies were identified as being eligible for inclusion to assess outcomes of pain (n = 6), fertility (n = 7), quality of life (n = 1), and disease progression (n = 3). Seven studies of interest were identified to evaluate patient preferences. There is evidence that operative laparoscopy may improve overall pain levels at 6 months compared with diagnostic laparoscopy (risk ratio [RR], 2.65; 95% confidence interval [CI], 1.61-4.34; p <.001; 2 RCTs, 102 participants; low-quality evidence). Because the quality of the evidence was very low, it is uncertain if operative laparoscopy improves live birth rates. Operative laparoscopy probably yields little or no difference regarding clinical pregnancy rates compared with diagnostic laparoscopy (RR, 1.29; 95% CI, 0.99-1.92; p = .06; 4 RCTs, 624 participants; moderate-quality evidence). It is uncertain if operative laparoscopy yields a difference in adverse outcomes when compared with diagnostic laparoscopy (RR, 1.98; 95% CI, 0.84-4.65; p = .12; 5 RCTs, 554 participants; very-low-quality evidence). No studies reported on the progression of endometriosis to a symptomatic state or progression of extent of disease in terms of volume of lesions and locations in asymptomatic women with endometriosis. We found no studies that reported on the timing of surgery. No quantitative or qualitative studies specifically aimed at elucidating the factors informing a woman's choice for surgery were identified. CONCLUSION: Operative laparoscopy may improve overall pain levels but may have little or no difference with respect to fertility-related or adverse outcomes when compared with diagnostic laparoscopy. Additional high-quality RCTs, including comparing surgery to medical management, are needed, and these should report adverse events as an outcome. Studies on patient preference in surgical decision making are needed (International Prospective Register of Systematic Review registration number: CRD42019135167).

Laparoscopic surgery for endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity and is associated with pain and subfertility. 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 painful symptoms and subfertility associated with endometriosis. SEARCH METHODS: This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group including searching CENTRAL, MEDLINE, EMBASE, PsycINFO, and trial registries from inception to July 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) were selected in which the effectiveness and safety of laparoscopic surgery used to treat pain or subfertility associated with endometriosis was compared with any other laparoscopic or robotic intervention, holistic or medical treatment or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Selection of studies, assessment of trial quality and extraction of relevant data were performed independently by two review authors with disagreements resolved by a third review author. The quality of evidence was evaluated using GRADE methods. MAIN RESULTS: Ten RCTs were included in the review. The studies randomised 973 participants experiencing pain or subfertility associated with endometriosis. Five RCTs compared laparoscopic ablation or excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus ablation. One RCT compared laparoscopic ablation versus diagnostic laparoscopy and injectable gonadotropin-releasing hormone analogue (GnRHa) (goserelin) with add-back therapy. Common limitations in the primary studies included lack of clearly-described blinding, failure to fully describe methods of randomisation and allocation concealment, and risk of attrition bias.Laparoscopic surgery was associated with decreased overall pain (measured as 'pain better or improved') compared with diagnostic laparoscopy, both at six months (odds ratio (OR) 6.58, 95% CI 3.31 to 13.10, 3 RCTs, 171 participants, I(2) = 0%, moderate quality evidence) and at 12 months (OR 10.00, 95% CI 3.21 to 31.17, 1 RCT, 69 participants, low quality evidence). Compared with diagnostic laparoscopy, laparoscopic surgery was also associated with an increased live birth or ongoing pregnancy rate (OR 1.94, 95% CI 1.20 to 3.16, P = 0.007, 2 RCTs, 382 participants, I(2) = 0%, moderate quality evidence) and increased clinical pregnancy rate (OR 1.89, 95% CI 1.25 to 2.86, P = 0.003, 3 RCTs, 528 participants, I(2) = 0%, moderate quality evidence). Two studies collected data on adverse events (including infection, vascular and visceral injury and conversion to laparotomy) and reported no events in either arm. Other studies did not report this outcome. The similar effect of laparoscopic surgery and diagnostic laparotomy on the rate of miscarriage per pregnancy was imprecise (OR 0.94, 95% CI 0.35 to 2.54, 2 studies, 112 women, moderate quality evidence).When laparoscopic ablation was compared with diagnostic laparoscopy plus medical therapy (GnRHa plus add-back therapy), more women in the ablation group reported that they were pain free at 12 months (OR 5.63, 95% CI 1.18 to 26.85, 1 RCT, 35 participants, low quality evidence).The difference between laparoscopic ablation and laparoscopic excision in the proportion of women reporting overall pain relief at 12 months on a VAS 0 to 10 pain scale was 0 (95% CI -1.22 to 1.22, P = 1.00, 1 RCT, 103 participants, low quality evidence). AUTHORS' CONCLUSIONS: There is moderate quality evidence that laparoscopic surgery to treat mild and moderate endometriosis reduces overall pain and increases live birth or ongoing pregnancy rates. There is low quality evidence that laparoscopic excision and ablation were similarly effective in relieving pain, although there was only one relevant study. More research is needed considering severe endometriosis, different types of pain associated with endometriosis (for example dysmenorrhoea (pain with menstruation)) and comparing laparoscopic interventions with holistic and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety.

Potential cures for endometriosis.

Treatment of endometriosis usually requires highly individualized management and varies depending on the presenting symptoms and the life stage of the patient. Surgical treatment of endometriosis starts with clinical recognition of the condition that may be enhanced by narrow band imaging. Surgery is effective in pain control and enhancing fertility. Tubal ligation or salpingectomy can be considered. Robotic surgery is unlikely to create a cure, but may assist surgery. Medical treatment including aromatase inhibitors may also be effective. Tubal flushing with lipiodol increases fecundity; other immunomodulators and neuromodulators may also be effective. Complementary therapies, however, have not been subjected to randomized clinical trials. Environmental factors, diet, and lifestyle modification may be effective.

Laparoscopic surgery for subfertility associated with endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation, often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by the division of adhesions. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of subfertility associated with endometriosis. The review aims to compare outcomes of laparoscopic surgical interventions compared to no treatment or medical treatment with regard to improved fertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (June 2009), Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009), EMBASE (1980 to June 2009), and reference lists of articles. SELECTION CRITERIA: Trials were selected if they were randomised and compared the effectiveness of laparoscopic surgery in the treatment of subfertility associated with endometriosis versus other treatment modalities or placebo. DATA COLLECTION AND ANALYSIS: Two studies were eligible for inclusion within the review. Both studies compared laparoscopic surgical treatment of minimal and mild endometriosis compared with diagnostic laparoscopy only. The recorded outcomes included live birth, pregnancy, fetal losses, and complications of surgery. MAIN RESULTS: When combining live birth rate and ongoing pregnancy after 20 weeks, meta-analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only. The odds ratio (OR) was 1.64 (95% confidence interval (Cl) 1.05 to 2.57) in favour of laparoscopic surgery. Meta-analysis also demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only in terms of clinical pregnancy rates, with an OR of 1.66 (95% Cl 1.09 to 2.51) favouring laparoscopic surgery. The results still need to be interpreted with caution as Marcoux 1997 reported a large positive effect of surgery whereas Gruppo Italiano reported a small negative effect. When considering fetal losses, meta-analysis did not demonstrate an effect of laparoscopic surgery when compared to diagnostic laparoscopy only. The OR was 1.33 (95% Cl 0.60 to 2.94) favouring diagnostic laparoscopy only. AUTHORS' CONCLUSIONS: The use of laparoscopic surgery in the treatment of subfertility related to minimal and mild endometriosis may improve future fertility.

Laparoscopic surgery for pelvic pain associated with endometriosis.

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions and relieve painful symptoms. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. SEARCH STRATEGY: For the update in July 2009 we searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched July 2009), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 July 2009), EMBASE (1980 July 2009), and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials were selected comparing the effectiveness of laparoscopic surgery used to treat pelvic pain associated with endometriosis, with other treatment modalities or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and extraction of relevant data was performed independently by two reviewers. MAIN RESULTS: Five studies were included in the meta-analysis, including three full papers and two conference reports. All the randomised controlled trials with the exception of Lalchandani 2003 compared different laparoscopic surgical techniques with diagnotic laparoscopy only. Lalchandani 2003 compared laparoscopic coagulation therapy with diagnostic laparoscopy and medical treatment. Three studies (Abbott 2004; Sutton 1994; Tutunaru 2006) reported the pain scores six months post operatively. Meta-analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 5.72 95%Cl 3.09 to 10.60 ; 171 participants, three trials, Analysis 1.1). A single study (Tutunaru 2006) reported pain scores twelve months after the procedure. Analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 7.72 95%Cl 2.97 to 20.06 ; 33 participants, one trial, Analysis 1.1). AUTHORS' CONCLUSIONS: Laparoscopic surgery results in improved pain outcomes when compared to diagnostic laparoscopy alone. There were few women diagnosed with severe endometriosis included in the meta-analysis and therefore any conclusions from this meta-analysis regarding treatment of severe endometriosis should be made with caution. It is not possible to draw conclusions from the meta-analysis which specific laparoscopic surgical intervention is most effective.