Charles E. Miller

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.

Background: Products of conception samples are often collected and analyzed to try to determine the cause of an early pregnancy loss. However, sample collection may not always be possible, and maternal cell contamination and culture failure can affect the analysis. Cell-free DNA-based analysis of a blood sample could be used as an alternative method in early pregnancy loss cases to detect if aneuploidies were present in the fetus. Methods: In this prospective study, blood samples from early pregnancy loss patients were analyzed for the presence of fetal aneuploidies using a modified version of a noninvasive prenatal testing assay for cell-free DNA analysis. Results from cell-free DNA analysis were compared against the gold standard, microarray analysis of products of conception samples. This study was registered with ClinicalTrials.gov, identifier: NCT04935138. Results: Of the 76 patient samples included in the final study cohort, 11 were excluded from performance calculations. The 65 patient samples included in the final analysis included 49 with an abnormal microarray result and 16 with a normal microarray result. Based on results from these 65 samples, the study found that genome-wide cell-free DNA analysis had a sensitivity of 73.5% with a specificity of 100% for the detection of fetal aneuploidies in early pregnancy loss cases. Conclusions: This prospective study provides further support for the utility of cell-free DNA analysis in detecting fetal aneuploidies in early pregnancy loss cases. This approach could allow for a noninvasive method of investigating the etiology of miscarriages to be made available clinically.

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.