Intra- and interobserver reproducibility of pelvic ultrasound for the detection and measurement of endometriotic lesions

STUDY QUESTION: What is the interobserver and intraobserver reproducibility of pelvic ultrasound for the detection of endometriotic lesions? SUMMARY ANSWER: Pelvic ultrasound is highly reproducible for the detection of pelvic endometriotic lesions. WHAT IS KNOWN ALREADY: Transvaginal ultrasound (TVS) has been widely adopted as the first-line assessment for the diagnosis and assessment of pelvic endometriosis. Severity of endometriosis as assessed by ultrasound has been shown to have good concordance with laparoscopy (kappa 0.79). The reproducibility of TVS for assessment of ovarian mobility and pouch of Douglas obliteration using the 'sliding sign' has already been described in the literature. However, there is no available data in the literature to demonstrate the intraobserver repeatability of measurements for endometriotic cysts and nodules. STUDY DESIGN SIZE DURATION: This was a prospective observational cross-sectional study conducted over a period of 12 months. We included 50 consecutive women who were all examined by two operators (A and B) during their clinic attendance. PARTICIPANTS/MATERIALS SETTING METHODS: The study was carried out in a specialist endometriosis centre. We included all consecutive women who had ultrasound scans performed independently by two experienced operators during the same visit to the clinic. The outcomes of interest were the inter- and intraobserver reproducibility for the detection of endometriotic lesions. We also assessed repeatability of the measurements of lesion size. MAIN RESULTS AND THE ROLE OF CHANCE: There was a good level of agreement between operator A and operator B in detecting the presence of pelvic endometriotic lesions (k = 0.72). There was a very good level of agreement between operators in identifying endometriotic cysts (k = 0.88) and a good level of agreement in identifying endometriotic nodules (k = 0.61). The inter- and intraobserver repeatability of measuring endometriotic cysts was excellent (intra-class correlation (ICC) ≥ 0.98). There was good interobserver measurement repeatability for bowel nodules (ICC 0.88), but the results for nodules in the posterior compartment were poor (ICC 0.41). The intraobserver repeatability for nodule size measurements was good for both operators (ICC ≥0.86). LIMITATIONS REASONS FOR CAUTION: Within this cohort, there was insufficient data to perform a separate analysis for nodule size in the anterior compartment. All examinations were performed within a specialised unit with a high prevalence of deep endometriosis. Our findings may not apply to operators without intensive ultrasound training in the diagnosis of pelvic endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: These findings are important because ultrasound has been widely accepted as the first-line investigation for the diagnosis of pelvic endometriosis, which often determines the need for future investigations and treatment. The detection and measurement of bowel nodules is essential for anticipation of surgical risk and planning surgical excision. STUDY FUNDING/COMPETING INTERESTS: The authors have no conflict of interest. No funding was obtained for this work

Ultrasound diagnosis of endometrial cancer by subjective pattern recognition in women with postmenopausal bleeding: a prospective inter-rater agreement and reliability study

OBJECTIVES: The objective of our study was to assess the inter-rater agreement and reliability of using subjective pattern recognition to diagnose endometrial cancer on ultrasound in women with postmenopausal bleeding. METHODS: This was a prospective cross-sectional study at a gynaecological rapid access clinic, between Oct 2016 - Dec 2017, where consecutive women with postmenopausal bleeding and endometrial thickness of ≥4.5mm on transvaginal ultrasound scan were included. We excluded women on hormone replacement therapy, tamoxifen or with a history of primary gynaecological malignancy. Two raters independently performed ultrasound examinations, blinded to each other's findings, and classified women into having uniformly thickened endometrium, benign polyp or endometrial cancer, by subjective pattern recognition. Inter-rater reliability of the ultrasound diagnoses was assessed by using Cohen's kappa statistics. All women subsequently underwent either outpatient endometrial biopsy, hysteroscopy or hysterectomy. RESULTS: Forty women were included in the study with a median age of 61 (IQR 57-69) and a median endometrial thickness of 11.0mm (IQR 6.2-20.3). Final histological analysis confirmed 16 (40%) women with endometrial cancer, 16 (40%) endometrial polyps, 4 (10%) atrophic endometrium, 3 (7%) proliferative endometrium and 1 (3%) endometrial hyperplasia. Inter-rater agreement for the ultrasound diagnoses of uniformly thickened endometrium, polyp and cancer, were 14/16 (87.5%), 22/30 (73.3%) and 28/34 (82.4%), respectively; the inter-rater reliability was good (κ = 0.69, 95% C.I. 0.49-0.88). When the ultrasound diagnoses were combined as either cancer or no cancer, the inter-rater agreement was 85% and the inter-rater reliability was also good (κ = 0.78, 95% C.I. 0.61-0.95). Rater A correctly identified 14/16 cancers and Rater B identified 15/16. Endometrial cancers were misdiagnosed as benign polyps on ultrasound in two women by Rater A, and in one woman by Rater B. The overall accuracies of Rater A and Rater B in differentiating between benign endometrial pathologies and malignancy were 90% and 85%, respectively. CONCLUSIONS: Our results showed good inter-rater reliability of subjective pattern recognition in diagnosing uniformly thickened endometrium, polyp and cancer on ultrasound in women with postmenopausal bleeding. Our findings should facilitate wider use of subjective pattern recognition in routine clinical practice

Development of the utero-placental circulation in cesarean scar pregnancies: A case-control study

BACKGROUND: Cesarean scar pregnancies (CSP) are at high risk of pregnancy complications including placenta previa with antepartum hemorrhage, placenta accreta spectrum (PAS) and uterine rupture. OBJECTIVE: To evaluate the development of the utero-placental circulation in the first half of pregnancy in ongoing CSP and compare it to pregnancies implanted in the lower uterine segment above a prior cesarean section scar with no evidence of PAS at delivery. MATERIAL AND METHODS: This was a retrospective case-control study conducted in two tertiary referral centers. The study group included 27 women diagnosed with a live caesarean scar pregnancy in the first trimester of pregnancy who elected to conservative management. The control group included 27 women diagnosed with a low-lying/placenta previa at 19-22 weeks of gestation who had a first and an early second trimester ultrasound examinations. In both groups, the first ultrasound examination was carried out at 6-10 weeks to establish pregnancy location, viability and to confirm the gestational age. The utero-placental and intra-placental vasculatures were examined using color Doppler imaging (CDI) and described semi quantitatively using CDI score 1-4. The remaining myometrial thickness (RMT) was recorded in the study group whereas in the controls the ultrasound features of prior cesarean scar were noted including the presence of a niche. Both CSP and controls had also ultrasound examinations at 11-14 and 19-22 weeks of gestation. RESULTS: The mean CDI vascularity score at the 6-10 weeks ultrasound examination was significantly (P <.001) higher in the CSP group than in the controls. The high vascularity scores 3 and 4 were recorded in 20/27 (74%) cases of the CSP group. There was no vascularity score of 4 and only 3/27 (11%) controls had vascularity score of 3. In 15/27 (55.6%) CSPs the RMT was < 2 mm. At the 11-14 weeks ultrasound examination, there was no significant difference between the groups for the number of cases with increased subplacental vascularity but 12 CSPs (44%) presented with one or more placental lacunae whereas there was no case with lacunae in the controls. In the 18 CSP that progressed into the third trimester, ten were diagnosed with placenta previa creta at birth, including 4 creta and 6 increta. At the 19-22 weeks ultrasound examination, eight of the ten PAS presented with subplacental hypervascularity out of which, six showed also placental lacunae. CONCLUSION: The vascular changes in the utero-placental and intervillous circulations in CSPs are due to the loss of the normal uterine structure in the scar area and the development of placental tissue in proximity of large diameter arteries of the outer uterine wall. The intensity of these vascular changes, development of PAS and risk of uterine rupture depend on the RMT of the cesarean scar defect at the start of pregnancy. A better understanding of the pathophysiology of the utero-placental vascular changes associated with CSP should help in identifying those cases that may develop major complications and thus contribute to counselling women about the risks associated with different management strategies

Risk prediction of major haemorrhage with surgical treatment of live cesarean scar pregnancies

Objective: To evaluate the association between demographic and ultrasound variables and major intra-operative blood loss during surgical transcervical evacuation of live caesarean scar pregnancies. Study Design: This was a retrospective cohort study conducted in a tertiary referral center between 2008 and 2019. We included all women diagnosed with a live caesarean scar ectopic pregnancy who chose to have surgical management in the study center. A preoperative ultrasound was performed in each patient. All women underwent transcervical suction curettage under ultrasound guidance. Our primary outcome was the rate of postoperative blood transfusion. The secondary outcomes were estimated intra-operative blood loss (ml), rate of retained products of conception, need for repeat surgery, need for uterine artery embolization and hysterectomy rate. Descriptive statistics were used to describe the variables. Univariate and multivariable logistic regression models were constructed using the relevant covariates to identify the significant predictors for severe blood loss. Results: During the study period, 80 women were diagnosed with a live caesarean scar pregnancy, of whom 62 (78%) opted for surgical management at our center. The median crown-rump length was 9.3 mm (range 1.4–85.7). Median blood loss at the time of surgery was 100 ml (range, 10–2300), and six women (10%; 95%CI 3.6–20) required blood transfusion. Crown-rump length and presence of placental lacunae were significant predictive factors for the need for blood transfusion and blood loss > 500 ml at univariate analysis (p < .01); on multivariate analysis, only crown-rump length was a significant predictor for need for blood transfusion (OR = 1.072; 95% CI 1.02–1.11). Blood transfusion was required in 6/18 (33%) cases with the crown-rump length ≥ 23 mm (≥9+0 weeks of gestation), but in none of 44 women presenting with a crown-rump length < 23 mm (p < .01). Conclusion: The risk of severe intraoperative bleeding and need for blood transfusion during or after surgical evacuation of live caesarean scar pregnancies increases with gestational age and is higher in the presence of placental lacunae. One third of women presenting at ≥ 9 weeks of gestation required blood transfusion and their treatment should be ideally arranged in specialized tertiary centers

Physical resolution of tubal ectopic pregnancy on ultrasound imaging following successful expectant management

RESEARCH QUESTION What is the time required for complete physical resolution of tubal ectopic pregnancies diagnosed on ultrasound imaging in women undergoing successful expectant management? DESIGN A prospective observational cohort study of 177 women who had successful expectant management of tubal ectopic pregnancy, who attended a single Early Pregnancy Unit between January 2014 and December 2018. All participants were monitored until their serum β-hCG dropped to non-pregnant levels and with two-weekly follow-up ultrasound scans until resolution of the pregnancy. RESULTS 112/177 (63.8%, 95% CI 56.3-70.9) of tubal ectopic pregnancies were indiscernible on ultrasound 2 weeks after serum β-hCG had returned to non-pregnant levels. In 8/177 (4.5%, 95% CI 2.0-8.7) physical resolution took longer than 78 days. There was a positive correlation between biochemical and physical resolution of tubal ectopic pregnancy (r=0.21, p=0.006). CONCLUSIONS Physical resolution of tubal ectopic pregnancy is often prolonged and is positively correlated with initial and maximum β-hCG levels. Our results indicate that β-hCG resolution cannot be used as the end-point of expectant management of tubal ectopic pregnancy, which should be considered when counselling women and planning for future pregnancies. KEY MESSAGE In a significant proportion, physical resolution of tubal ectopic pregnancy takes several weeks following the return of serum β-hCG to non-pregnant levels. Women should be advised to delay trying for another pregnancy for three months, to avoid resolving pregnancies being misdiagnosed as new ones and to reduce the theoretical risk of recurrent ectopic, due to temporary tubal blockage by the resolving trophoblast

A prospective evaluation of the IOTA Logistic Regression Models (LR1 and LR2) in comparison to Subjective Pattern Recognition for the diagnosis of ovarian cancer in the outpatient setting

OBJECTIVES: To determine whether IOTA diagnostic models developed for pre-operative diagnosis of ovarian cancer could also be used to differentiate between benign and malignant adnexal tumours in the population of women attending gynaecology outpatient clinics. METHODS: All women referred to our outpatient clinic were first examined by a Level II ultrasound operator. In those diagnosed with adnexal tumours the IOTA LR1/2 protocol was used to evaluate the masses. The LR1 and LR2 models were then used to assess the risk of malignancy. Subsequently women were also examined by a Level 3 examiner who used pattern recognition to differentiate between benign and malignant tumours. Women with an ultrasound diagnosis of malignancy were offered surgery whilst asymptomatic women with presumed benign lesions were offered conservative management with a minimum follow-up of 12 months. The initial diagnosis was compared with two reference standards: histological findings and/or a comparative assessment of tumour morphology on follow-up ultrasound scans. All women in whom tumour classification on follow-up changed from benign to malignant were offered surgery. RESULTS: 489 women who had either or both of the reference standards were included into the final analysis. Their mean age was 50 years (range 16-91) and 45% of them were menopausal. 342/489 (69.9%) women had surgery and 147/489 (30.1%) were managed conservatively. The malignancy rate was 137/489 (28.0%). Overall sensitivities of LR1 and LR2 for the diagnosis of malignancy were 97.1% (95% CI: 92.7-99.2) and 94.9% (95%CI: 89.8-97.9) and specificities were 77.3% (95%CI: 72.5-81.5) and 76.7% (95%CI; 71.9-81.0) respectively (p>0.05). In comparison to pattern recognition [Sensitivity 94.2% (95% CI: 88.8 to 97.4); specificity 96.3% (95% CI: 93.8 to 98.0)], the specificities of IOTA models were significantly lower. (p < 0.0001) A significantly higher number of women would have been offered surgery for suspected cancer if women were assessed using the IOTA models instead of pattern recognition [213/489 (43.6%) versus 142/489 (29.0%)] (p<0.001). CONCLUSIONS: IOTA models maintained their high sensitivity when used in the outpatient setting. Specificity was relatively low which indicates that a significant proportion of women would have been offered unnecessary surgery for suspected ovarian cancer. These findings show that IOTA models could be used as a first stage test to diagnose ovarian cancer in the outpatient setting but a different second stage test is required to minimise the number of false positive findings

Single dose systemic methotrexate versus expectant management for treatment of tubal ectopic pregnancy: A placebo-controlled randomised trial

OBJECTIVE: Methotrexate is routinely used worldwide for medical treatment of clinically stable women with tubal ectopic pregnancies. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicentre randomised trial study was to compare the success rates of methotrexate with placebo for the conservative treatment of tubal ectopic pregnancies. METHODS: The study was multicentre; it took place in three UK early pregnancy units between January 2006 and June 2014. Inclusion criteria were clinically stable women with a conclusive ultrasound diagnosis of a tubal ectopic pregnancy presenting with low serum β-hCG <1500IU/l. Women were randomly assigned to single systemic injection of methotrexate 50mg/m(2) or placebo. The primary outcome of the study was a binary indicator for success of conservative management, defined as resolution of clinical symptoms and decline of serum β-hCG to <20IU/l or negative urine pregnancy test without the need for any additional medical intervention. An intention to treat analysis was followed. RESULTS: We recruited a total of 80 women: 42 to methotrexate and 38 to placebo. The two arms of the study were balanced in terms of age, ethnicity, obstetric histories, pregnancy characteristics and serum β-hCG and progesterone. The proportions of successes were similar: 83% with methotrexate and 76% with placebo. On univariate analysis, this difference was not statistically significant (χ2(1df) = 0.53; P = 0.23). On multivariate logistic regression, β-hCG was the only covariate which was significantly associated with outcome. The odds of failure increased by 0.15% for each unit increase in β-hCG (OR=1.0015; 95% CI 1.0002 to 1.003; P = 0.02). In 14 women presenting with serum hCG 1000-1500IU/l the success of expectant management was 33% compared to 62% in the methotrexate arm. Although this result was not statistically significant a larger sample size would give us greater power to detect a difference in this subgroup of women, In women with successful conservative management there was no significant difference in median resolution times between methotrexate and placebo arms [17.5 days (IQR 14 - 28.0) (n = 30)] vs [14 days (IQR 7 - 29.5) (n = 25)] (P = 0.73) CONCLUSION: The results of our study do not support routine use of methotrexate for the treatment of clinically stable women diagnosed with tubal ectopic pregnancies presenting with low serum hCG <1500IU/l. Further work is required to identify a subgroup of women with tubal ectopic pregnancies and hCG≥1500IU/l in whom methotrexate may offer a safe and cost-effective alternative to surgery

Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial

BACKGROUND: Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy. METHODS: We performed a multicentre, randomised, double-blind, placebo-controlled trial across 50 UK hospitals. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m2) and randomised (1:1 ratio) to 7 days of additional oral gefitinib (250 mg daily) or placebo. The primary outcome, analysed by intention to treat, was surgical intervention to resolve the ectopic pregnancy. Secondary outcomes included time to resolution of ectopic pregnancy and serious adverse events. This trial is registered at the ISRCTN registry, ISCRTN 67795930. FINDINGS: Between Nov 2, 2016, and Oct 6, 2021, 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). Three participants in the placebo group withdrew. Surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and in 47 (29%) of 160 participants in the placebo group (adjusted risk ratio 1·15, 95% CI 0·85 to 1·58; adjusted risk difference -0·01, 95% CI -0·10 to 0·09; p=0·37). Without surgical intervention, median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group (subdistribution hazard ratio 1·03, 95% CI 0·75 to 1·40). Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and in six (4%) of 162 participants in the placebo group. Diarrhoea and rash were more common in the gefitinib group. INTERPRETATION: In women with a tubal ectopic pregnancy, adding oral gefitinib to parenteral methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions. FUNDING: National Institute of Health Research

Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG).

Laparoscopy is widely utilised to diagnose and treat acute and chronic, gynaecological and general surgical conditions. It has only been in recent years that laparoscopy has become an acceptable surgical alternative to open surgery in pregnancy. To date there is little clinical guidance pertaining to laparoscopic surgery in pregnancy. This is why the BSGE commissioned this guideline. MEDLINE, EMBASE, CINAHL and the Cochrane library were searched up to February 2017 and evidence was collated and graded following the NICE-approved process. The conditions included in this guideline are laparoscopic management of acute appendicitis, acute gall bladder disease and symptomatic benign adnexal tumours in pregnancy. The intended audience for this guideline is obstetricians and gynaecologists in secondary and tertiary care, general surgeons and anaesthetists. However, only laparoscopists who have adequate laparoscopic skills and who perform complex laparoscopic surgery regularly should undertake laparoscopy in pregnant women, since much of the evidence stems from specialised centres

A protocol for developing a core outcome set for ectopic pregnancy

BACKGROUND: Randomised controlled trials (RCTs) evaluating ectopic pregnancy have reported many different outcomes, which are themselves often defined and measured in distinct ways. This level of variation results in an inability to compare results of individual RCTs. The development of a core outcome set to ensure outcomes important to key stakeholders are collected consistently will guide future research in ectopic pregnancy. STUDY AIM: To develop and implement a core outcome set to guide future research in ectopic pregnancy. METHODS AND ANALYSIS: We have established an international steering group of key stakeholders, including healthcare professionals, researchers, and individuals with lived experience of ectopic pregnancy. We will identify potential outcomes from ectopic pregnancy from a comprehensive literature review of published randomised controlled trials. We will then utilise a modified Delphi method to prioritise outcomes. Subsequently, key stakeholders will be invited to score potential core outcomes on a nine-point Likert scale, ranging from 1 (not important) to 9 (critical). Repeated reflection and rescoring should promote whole and individual stakeholder group convergence towards consensus ‘core’ outcomes. We will also establish standardised definitions and recommend high-quality measurements for individual core outcomes. TRIAL REGISTRATION: COMET 1492. Registered in November 2019