Postoperative adhesions represent a frequent complication of abdominal surgery. Adhesions can result from infection, ischemia, and foreign body reaction, but commonly develop after any surgical procedure. The morbidity caused by adhesions affects quality of life and, therefore, it is paramount to continue to raise awareness and scientific recognition of the burden of adhesions in healthcare and clinical research. This 2021 Global Expert Consensus Group worked together to produce consented statements to guide future clinical research trials and advise regulatory authorities. It is critical to harmonize the expectations of research, to both develop and bring to market improved anti-adhesion therapies, with the ultimate, shared goal of improved patient outcomes.

Objective: To report 2-year results of sonography-guided transcervical fibroid ablation (TFA) using the Sonata ^® system in women with symptomatic uterine fibroids. Design: This is a prospective multicenter single-arm interventional trial. Methods: Premenopausal women with up to 10 clinically relevant uterine fibroids, each ranging from 1 to 5 cm in diameter, were treated with sonography-guided TFA on an outpatient basis and returned for regular follow-up visits for 2 years. Assessed outcomes included changes in symptom severity, heath-related quality of life, general health status, work and activity limitations, treatment satisfaction, adverse events, surgical reintervention, and occurrence of pregnancy and associated outcomes. Results: Among 147 enrolled women, 125 (85%) returned for follow-up at 2 years. Compared with baseline, symptom severity decreased from 55 ± 19 to 24 ± 18 ( p < 0.001), health-related quality of life increased from 40 ± 21 to 83 ± 19 ( p < 0.001), and EuroQol 5-Dimension scores increased from 0.72 ± 0.21 to 0.89 ± 0.14 ( p < 0.001). Overall treatment satisfaction at 2 years was 94%. The mean percentage of missed work time, overall work impairment, and activity impairment significantly decreased at follow-up. Through 2 years, surgical reintervention for heavy menstrual bleeding was performed in 5.5% of patients. One singleton pregnancy occurred with a normal peripartum outcome. Conclusions: TFA treatment with the Sonata system provides significant clinical improvement through 2 years postablation, with a low incidence of surgical reintervention. Other favorable outcomes included a rapid return to work and substantial improvements in quality of life, symptom severity, work productivity, and activity levels.

Elagolix, an approved oral treatment for endometriosis-associated pain, has been associated with hypoestrogenic effects when used as monotherapy. Hormonal add-back therapy has the potential to mitigate these effects. To evaluate efficacy, tolerability, and bone density outcomes of elagolix 200 mg twice daily with 1 mg estradiol /0.5 mg norethindrone acetate (add-back) therapy once daily compared with placebo in premenopausal women with moderate-to-severe endometriosis-associated pain. This ongoing, 48-month, phase 3 study consists of a 12-month, double-blind period, with randomization 4:1:2 to elagolix 200 mg twice daily with add-back therapy, elagolix 200 mg twice daily monotherapy for 6 months followed by elagolix with add-back therapy, or placebo. The co-primary endpoints were proportion of patients with clinical improvement (termed "responders") in dysmenorrhea and nonmenstrual pelvic pain at month 6. We report 12-month results on efficacy of elagolix with add-back therapy versus placebo in reducing dysmenorrhea, nonmenstrual pelvic pain, dyspareunia, and fatigue. Tolerability assessments include adverse events and change from baseline in bone mineral density. A total of 679 patients were randomized to elagolix with add-back therapy (n=389), elagolix monotherapy (n=97), or placebo (n=193). Compared with patients randomized to placebo, a significantly greater proportion of patients randomized to elagolix with add-back therapy responded with clinical improvement in dysmenorrhea (62.8% versus 23.7%; P≤.001) and nonmenstrual pelvic pain (51.3% versus 36.8%; P≤.001) at 6 months. Compared with placebo, elagolix with add-back therapy produced significantly greater improvement from baseline in 7 hierarchically ranked secondary endpoints including dysmenorrhea (months 12, 6, 3), nonmenstrual pelvic pain (months 12, 6, 3), and fatigue (months 6) (all P<.01). Overall, the incidence of adverse events was 73.8% with elagolix plus add-back therapy and 66.8% with placebo. The rate of severe and serious adverse events did not meaningfully differ between treatment groups. Study drug discontinuations associated with adverse events were low in patients receiving elagolix with add-back therapy (12.6%) and those receiving placebo (9.8%). Patients randomized to elagolix monotherapy exhibited decreases from baseline in bone mineral density of -2.43% (lumbar spine), -1.54% (total hip), and -1.78% (femoral neck) at month 6. When add-back therapy was added to elagolix at month 6, the change from baseline in bone mineral density remained in a similar range of -1.58% to -1.83% at month 12. However, patients who received elagolix plus add-back therapy from baseline exhibited little change from baseline in bone mineral density (<1% change) at months 6 and 12. Compared with placebo, elagolix with add-back therapy resulted in significant, clinically meaningful improvement in dysmenorrhea, nonmenstrual pelvic pain, and fatigue at 6 months that continued until month 12 for both dysmenorrhea and nonmenstrual pelvic pain. Elagolix with add-back therapy was generally well tolerated. Loss of bone mineral density at 12 months was greater in patients who received elagolix with add-back therapy than those who received placebo. However, the change in bone mineral density with elagolix plus add-back therapy was < 1% and was attenuated compared with bone loss observed with elagolix monotherapy.

Background/Objectives: The diagnosis and treatment of endometriosis should be based on the best available evidence. Emphasising the risk of bias, the pyramid of evidence has the double-blind, randomised controlled trial and its meta-analyses on top. After the grading of all evidence by a group of experts, clinical guidelines are formulated using well-defined rules. Unfortunately, the impact of evidence-based medicine (EBM) on the management of endometriosis has been limited and, possibly, occasionally harmful. Methods: For this research, the inherent problems of diagnosis and treatment were discussed by a working group of endometriosis and EBM specialists, and the relevant literature was reviewed. Results: Most clinical decisions are multivariable, but randomized controlled trials (RCTs) cannot handle multivariability because adopting a factorial design would require prohibitively large cohorts and create randomization problems. Single-factor RCTs represent a simplification of the clinical reality. Heuristics and intuition are both important for training and decision-making in surgery; experience, Bayesian thinking, and learning from the past are seldom considered. Black swan events or severe complications and accidents are marginally discussed in EBM since trial evidence is limited for rare medical events. Conclusions: The limitations of EBM for managing endometriosis and the complementarity of multivariability, heuristics, Bayesian thinking, and experience should be recognized. Especially in surgery, the value of training and heuristics, as well as the importance of documenting the collective experience and of the prevention of complications, are fundamental. These additions to EBM and guidelines will be useful in changing the Wild West mentality of surgery resulting from the limited scope of EBM data because of the inherent multivariability, combined with the low number of similar interventions.