Obstetric outcomes in women with pelvic endometriosis: a prospective cohort study.

OBJECTIVE: To determine whether obstetric outcomes differ between women with endometriosis and those without, where all women undergo first-trimester screening for endometriosis. DESIGN: A prospective observational cohort study. SETTING: The Early Pregnancy Unit at University College London Hospital, United Kingdom. PATIENTS: Women with a live pregnancy progressing beyond 12 weeks' gestation and concurrent endometriosis (n = 110) or no endometriosis (n = 393). INTERVENTION: All women underwent a pelvic ultrasound examination in early pregnancy to examine for the presence of endometriosis and uterine abnormalities. MAIN OUTCOME MEASURES: The primary outcome of interest was preterm birth, defined as delivery before 37 completed weeks' gestation. Secondary outcomes included late miscarriage, antepartum hemorrhage, placental site disorders, gestational diabetes, hypertensive disorders of pregnancy, neonates small for gestational age, mode of delivery, intrapartum sepsis, postpartum hemorrhage, and admission to the neonatal unit. RESULTS: Women with a diagnosis of endometriosis did not have statistically significantly higher odds of preterm delivery (adjusted odds ratio [aOR] 1.85 [95% confidence interval {CI} 0.50-6.90]), but they did have higher odds of postpartum hemorrhage during cesarean section (aOR 3.64 [95% CI 2.07-6.35]) and admission of their newborn infant to the neonatal unit (aOR 3.24 [95% CI 1.08-9.73]). Women with persistent or recurrent deep endometriosis after surgery also had higher odds of placental site disorders (aOR 8.65 [95% CI 1.17-63.71]) and intrapartum sepsis (aOR 3.47 [95% CI 1.02-11.75]). CONCLUSION: We observed that women with endometriosis do not have higher odds of preterm delivery, irrespective of their disease subtype. However, they do have higher odds of postpartum hemorrhage during the cesarean section and newborn admission to the neonatal unit.

Development of deep pelvic endometriosis following acute haemoperitoneum: a prospective ultrasound study.

STUDY QUESTION: Is acute haemoperitoneum that is managed conservatively a precursor of deep endometriosis? SUMMARY ANSWER: Our study provides evidence to suggest that acute haemoperitoneum may lead to the development of deep endometriosis in a significant proportion of cases. WHAT IS KNOWN ALREADY: A recent pilot study was the first to suggest that acute haemoperitoneum could be a precursor of deep endometriosis. However, the sample size was small, and the follow-up was not standardized owing to unknown rates of clot absorption and development of endometriosis. STUDY DESIGN SIZE DURATION: This was a prospective observational cohort study conducted at a single centre over a 31-month period. A required sample size of 30 was calculated using results from a previous study, with a minimum of 15 women each in the groups with and without significant haemoperitoneum (study and control groups, respectively). A total of 59 women were recruited to the study and eight were lost to follow-up. The final sample comprised 51 women, 15 in the study group and 36 in the control group. PARTICIPANTS/MATERIALS SETTING METHODS: All non-pregnant, premenopausal women aged 18-50 years who consecutively presented to our dedicated gynaecological diagnostic unit with severe acute lower abdominal pain were eligible for this study. We only included women who were clinically stable and were suitable for conservative management. Those with prior history or evidence of endometriosis on their initial ultrasound scan, previous hysterectomy, or bilateral oophorectomy were excluded. Participants had standardized follow-up visits for 6 months, with pelvic ultrasound scans and the British Society of Gynaecological Endoscopy pelvic pain questionnaires completed at each visit. The primary outcome was the sonographically confirmed presence of newly formed endometriosis. Secondary outcomes were the presence and change of pelvic pain symptoms and health-related quality of life (HR-QOL). MAIN RESULTS AND THE ROLE OF CHANCE: After completion of follow-up, 7/15 (47%; 95% CI 21.3-71.4%) women presenting with acute haemoperitoneum (study group) developed sonographic evidence of deep endometriosis, compared to 0/36 (0%; 97.5% CI 0.0-9.7%) women in the control group. A ruptured functional haemorrhagic cyst was the most common cause of haemoperitoneum, occurring in 13/15 cases (87%). The time from the initial event to sonographic evidence of endometriosis varied from 2 to 6 months. The EuroQol visual analogue scores were not significantly different at baseline between the groups that developed and did not develop endometriosis [28 (interquartile range (IQR) 15-40, n = 6) vs 56 (IQR 35-75, n = 44), P = 0.09], while the EuroQol-5D values were lower in the endometriosis group [-0.01 (IQR -0.07 to 0.19, n = 6) vs 0.62 (IQR 0.24-0.73, n = 44), P = 0.002]. At 6 months, the EuroQol-5D scores were improved in both groups, but remained significantly lower in the endometriosis group compared to the no endometriosis group [0.69 (IQR 0.66-0.80, n = 6) vs 0.85 (IQR 0.76-1.00, n = 44), P = 0.03]. There was no clinically relevant difference in the pelvic pain scores at either time point. LIMITATIONS REASONS FOR CAUTION: It remains uncertain whether minimal, superficial endometriosis existed at commencement of the study and had a role in the development of deep endometriosis. Although the ultrasound findings were in keeping with deep endometriosis, this was not confirmed histologically. The pelvic pain and HR-QOL findings could have been influenced by the baseline scores being taken when the patient was admitted with acute pain. Also, the sample size was too small to draw reliable conclusions regarding the impact of newly developed endometriosis on QoL. WIDER IMPLICATIONS OF THE FINDINGS: Our study provides further evidence showing that significant haemoperitoneum may be a precursor of deep endometriosis. Haemodynamically stable women presenting with acute pelvic pain and significant haemoperitoneum should be counselled about the risk of developing deep endometriosis. Interventional studies should be carried out in the future to see whether laparoscopy and pelvic washout could prevent development of deep endometriosis. Preventative strategies, including treatment to suppress ovulation and formation of functional cysts, should be further investigated. This includes the combined and progesterone-only contraceptive pills. Larger future studies are also required to assess women over a longer period of time, with adjustment for confounding factors, to evaluate a possible effect on HR-QOL and pain symptoms. STUDY FUNDING/COMPETING INTERESTS: Funding was obtained from The Gynaecology Ultrasound Centre, London, UK. TT received personal fees from GE, Samsung, Medtronic, and Merck for lectures on ultrasound. TT also received a postdoctoral grant from the South-Eastern Norwegian Health Authority (grant number 2020083). TRIAL REGISTRATION NUMBER: researchregistry6472.

Surgical evacuation combined with Shirodkar cervical suture and selective uterine artery embolization: A fertility preserving treatment for 10-15 weeks' live cesarean scar ectopic pregnancies.

INTRODUCTION: Cesarean scar ectopic pregnancies (CSEPs) are associated with significant maternal morbidity and termination is often recommended in the early first trimester. Management of more advanced cases is challenging due to higher risks of major intraoperative hemorrhage. Hysterectomy is currently the intervention of choice for advanced cases. This study aimed to investigate if advanced live CSEPs could be managed effectively conservatively using suction curettage and interventional radiology. MATERIAL AND METHODS: A retrospective single-center cohort study was performed. A total of 371 women diagnosed with CSEP were identified between January 2008 and January 2023. A total of 6% (22/371) women had an advanced live CSEP with crown-rump length (CRL) of ≥40 mm (≥10 weeks' gestation). Of these, 77% (17/22) opted for surgical intervention, whilst the remaining five continued their pregnancies. A preoperative ultrasound was performed in each patient. All women underwent suction curettage under ultrasound guidance and insertion of Shirodkar cervical suture as a primary hemostatic measure combined with uterine artery embolization (UAE) if required. The primary outcome was rate of blood transfusion. Secondary outcomes were estimated intraoperative blood loss, UAE, intensive care unit admission, reintervention, hysterectomy, hospitalization duration and rate of retained products of conception. Descriptive statistics were used to describe these variables. RESULTS: Median CRL of the 17 patients included was 54.1 mm (range: 40.0-85.7) and median gestational age based on CRL was 12 + 3 weeks (range: 10 + 6-15 + 0). On preoperative ultrasound scan placental lacunae were recorded in 76% (13/17) of patients and color Doppler score was ≥3 in 67% (10/15) of patients. At surgery, Shirodkar cervical suture was used in all cases. It was successful in achieving hemostasis by tamponade in 76% (13/17) of patients. In the remaining 24% (4/17) patients tamponade failed to achieve complete hemostasis and UAE was performed to stop persistent arterial bleeding into the uterine cavity. Median intraoperative blood loss was 800 mL (range: 250-2500) and 41% (7/17) women lost >1000 mL. 35% (6/17) needed blood transfusion. No women required hysterectomy. CONCLUSIONS: Surgical evacuation with Shirodkar cervical suture and selective UAE is an effective treatment for advanced live CSEPs.

Prior-Guided Attribution of Deep Neural Networks for Obstetrics and Gynecology.

Obstetrics and gynecology (OB/GYN) are areas of medicine that specialize in the care of women during pregnancy and childbirth and in the diagnosis of diseases of the female reproductive system. Ultrasound scanning has become ubiquitous in these branches of medicine, as breast or fetal ultrasound images can lead the sonographer and guide him through his diagnosis. However, ultrasound scan images require a lot of resources to annotate and are often unavailable for training purposes because of confidentiality reasons, which explains why deep learning methods are still not as commonly used to solve OB/GYN tasks as in other computer vision tasks. In order to tackle this lack of data for training deep neural networks in this context, we propose Prior-Guided Attribution (PGA), a novel method that takes advantage of prior spatial information during training by guiding part of its attribution towards these salient areas. Furthermore, we introduce a novel prior allocation strategy method to take into account several spatial priors at the same time while providing the model enough degrees of liberty to learn relevant features by itself. The proposed method only uses the additional information during training, without needing it during inference. After validating the different elements of the method as well as its genericity on a facial analysis problem, we demonstrate that the proposed PGA method constantly outperforms existing baselines on two ultrasound imaging OB/GYN tasks: breast cancer detection and scan plane detection with segmentation prior maps.

Performance of the WID-qEC test versus sonography to detect uterine cancers in women with abnormal uterine bleeding (EPI-SURE): a prospective, consecutive observational cohort study in the UK.

BACKGROUND: To detect uterine cancer, simpler and more specific index tests are needed to triage women with abnormal uterine bleeding to a reference histology test. We aimed to compare the performance of conventional index imaging tests with the novel WID-qEC DNA methylation test in terms of detecting the presence or absence of uterine cancers in women with abnormal uterine bleeding. METHODS: EPI-SURE was a prospective, observational study that invited all women aged 45 years and older with abnormal uterine bleeding attending a tertiary gynaecological diagnostic referral centre at University College London Hospital (London, UK) to participate. Women meeting these inclusion criteria who consented to participate were included. Pregnant women and those with previous hysterectomy were excluded. A cervicovaginal sample for the WID-qEC test was obtained before standard assessment using index imaging tests (ie, ultrasound) and, where applicable, reference histology (ie, biopsy, hysteroscopy, or both) was performed. Technicians performing the WID-qEC test were masked to the final clinical outcome. The result of the WID-qEC test is defined as the sum of the percentage of fully methylated reference (ΣPMR) of the ZSCAN12 and GYPC regions. Patients were followed until diagnostic resolution or until June 12, 2023. The primary outcome was to assess the real-world performance of the WID-qEC test in comparison with ultrasound with regard to the area under the receiver-operating-characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. EPI-SURE is registered with ISRCTN (16815568). FINDINGS: From June 1, 2022, to Nov 24, 2022, 474 women were deemed eligible to participate. 74 did not accept the invitation to participate, and one woman withdrew after providing consent. 399 women were included in the primary analysis cohort. Based on 603 index imaging tests, 186 (47%) women were recommended for a reference histology test (ie, biopsy, hysteroscopy, or both). 12 women were diagnosed with cancer, 375 were not diagnosed with cancer, and 12 had inconclusive clinical outcomes and were considered study dropouts. 198 reference histology test procedures detected nine cases of cancer and missed two; one further cancer was directly diagnosed at hysterectomy without a previous reference test. The AUC for detection of uterine cancer based on endometrial thickness in mm was 87·2% (95% CI 71·1-100·0) versus 94·3% (84·7-100·0) based on WID-qEC (p=0·48). Endometrial thickness assessment on ultrasound scan was possible in 379 (95%) of the 399 women and a prespecified cut-off of 4·5 mm or more showed a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 79·1% (74·5-82·9), a positive predictive value of 11·8% (6·5-20·3), and a negative predictive value of 99·6% (98·0-99·9). The WID-qEC test was possible in 390 (98%) of the 399 patients with a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 92·1% (88·9-94·4), a positive predictive value of 25·6% (14·6-41·1), and a negative predictive value of 99·7% (98·3-99·9), when the prespecified threshold of 0·03 ΣPMR or more was applied. When a higher threshold (≥0·3 ΣPMR) was applied the specificity increased to 97·3% (95% CI 95·1-98·5) without a change in sensitivity. INTERPRETATION: The WID-qEC test delivers fast results and shows improved performance compared with a combination of imaging index tests. Triage of women with abnormal uterine bleeding using the WID-qEC test could reduce the number of women requiring histological assessments for identification of potential malignancy and specifically reduce the false positive rate. FUNDING: The Eve Appeal, Land Tirol, and the European Research Council under the European Union's Horizon 2020 Research and Innovation Programme.

Intra- and interobserver reproducibility of transvaginal ultrasound for the detection and measurement of endometriotic lesions of the bowel.

INTRODUCTION: The number and invasion depth of endometriotic bowel lesions, total length of bowel affected by endometriosis, lesion-to-anal verge distance, and extent of pouch of Douglas obliteration are important factors in preoperatively determining risk and complexity of endometriosis surgery. The intra- and interobserver reproducibility of transvaginal ultrasound in the evaluation of many of these parameters has not yet been investigated. Our study aimed to assess the intra- and interobserver reproducibility of transvaginal ultrasound between an experienced and less experienced examiner for all of these parameters. MATERIAL AND METHODS: This prospective observational cross-sectional study was conducted between July 2019 and November 2020. Fifty consecutive premenopausal women who underwent transvaginal ultrasound examination in our clinic for the first time, were examined by the same two operators during the same attendance. Outcomes of interest were the inter-rater reproducibility of transvaginal ultrasound for detecting the presence, number, depth and size of bowel endometriotic nodules, lesion-to-anal-verge distance, total length of bowel affected, and pouch of Douglas obliteration. The intraobserver reproducibility was assessed for the continuous parameters. Cohen's kappa (κ) statistic, Cohen's weighted kappa (κ), proportions of agreement, intraclass correlation coefficient (ICC) and Bland-Altman limits of agreement were used to assess the reproducibility of the parameters. RESULTS: The inter-rater agreement and reliability were very good for identifying bowel endometriosis, the number and invasion depth of bowel nodules, determining whether the maximum nodule length was <3 cm, and lesion-to-anal-verge distance <8 cm (proportion of agreement 0.92, 0.94, 0.97, 0.94, 0.96; κ 0.92, 0.91, 0.92, 0.82, 0.89). The inter-rater agreement and reliability were good for assessing pouch of Douglas obliteration (proportion of agreement 0.86, κ 0.80). The intra-rater reliability for the mean nodule diameter (ICC 0.93 and 0.97) and total length of bowel affected (ICC 0.94 and 0.91) were excellent for operators A and B, respectively. The inter-rater reliability for the mean nodule diameter was good (ICC 0.80), and moderate for the total length of bowel affected (ICC 0.70). The Bland-Altman limits of agreement demonstrated clinically acceptable ranges for these two parameters. CONCLUSIONS: This study demonstrated a high intra- and inter-rater reproducibility of transvaginal ultrasound in the diagnosis of bowel endometriosis and measurement of its various components.

Surgical evacuation of cesarean scar ectopic pregnancies.

Cesarean scar ectopic pregnancy is associated with significant maternal morbidity, including severe hemorrhage, need for the blood transfusion and hysterectomy. Early diagnosis is therefore key in ensuring timely management, with consensus being that treatment before 9 weeks of gestation leads to reduced morbidity. There is no universally adopted management protocol for cesarean scar ectopic pregnancy, but surgical management generally has a higher success rate than medical management. The primary surgical treatment modalities are suction evacuation versus resection of the pregnancy via multiple routes. Adjuncts that have been shown to successfully minimize bleeding with surgical management include cervical cerclage, balloon catheter, and uterine artery embolization. However, there remains a lack of high-quality evidence regarding what is the best surgical treatment option for cesarean scar ectopic pregnancy, and therefore it is essential that clinicians provide tailored management to patients considering the presenting symptoms and local expertise with various surgical techniques.

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.

A Simple Cervicovaginal Epigenetic Test for Screening and Rapid Triage of Women With Suspected Endometrial Cancer: Validation in Several Cohort and Case/Control Sets.

PURPOSE: Endometrial cancer (EC) incidence has been rising over the past 10 years. Delays in diagnosis reduce survival and necessitate more aggressive treatment. We aimed to develop and validate a simple, noninvasive, and reliable triage test for EC to reduce the number of invasive diagnostic procedures and improve patient survival. METHODS: We developed a test to screen and triage women with suspected EC using 726 cervical smear samples from women with and without EC, and validated the test in 562 cervicovaginal samples using three different collection methods (cervical smear: n = 248; vaginal swab: n = 63; and self-collection: n = 251) and four different settings (case/control: n = 388; cohort of women presenting with postmenopausal bleeding: n = 63; a cohort of high-risk women with Lynch syndrome: n = 25; and a nested case/control setting from a screening cohort and samples taken up to 3 years before EC diagnosis: n = 86). RESULTS: We describe the Women's cancer risk IDentification - quantitative polymerase chain reaction test for Endometrial Cancer (WID-qEC), a three-marker test that evaluates DNA methylation in gene regions of GYPC and ZSCAN12. In cervical, self-collected, and vaginal swab samples derived from symptomatic patients, it detected EC with sensitivities of 97.2% (95% CI, 90.2 to 99.7), 90.1% (83.6 to 94.6), and 100% (63.1 to 100), respectively, and specificities of 75.8% (63.6 to 85.5), 86.7% (79.3 to 92.2), and 89.1% (77.8 to 95.9), respectively. The WID-qEC identified 90.9% (95% CI, 70.8 to 98.9) of EC cases in samples predating diagnosis up to 1 year. Test performance was similar across menopausal status, age, stage, grade, ethnicity, and histology. CONCLUSION: The WID-qEC is a noninvasive reliable test for triage of women with symptoms suggestive of ECs. Because of the potential for self-collection, it could improve early diagnosis and reduce the reliance for in-person visits.

Ultrasound Prediction of Segmental Bowel Resection in Women with Rectovaginal Endometriosis: A Single-Center Experience.

STUDY OBJECTIVE: To retrospectively evaluate the ability of routinely collected preoperative ultrasound data to predict bowel resection during surgery for rectovaginal endometriosis. DESIGN AND SETTING: Patients at the University College London Hospital who underwent surgery for rectovaginal endometriosis during a 6-year period were identified from the prospectively generated hospital (British Society for Gynaecological Endoscopy) database. Imaging data were collected and analyzed to determine associations with the requirement for bowel resection. PATIENTS: We evaluated 228 consecutive women undergoing bowel surgery (shave, disc resection, or segmental resection) for rectovaginal endometriosis. INTERVENTIONS: The patients in our study underwent surgical resection of rectovaginal endometriosis and interventions included shave, disc resection, and segmental resection of the bowel. All patients underwent a preoperative transvaginal ultrasound to assess the extent of endometriosis. MEASUREMENTS AND MAIN RESULTS: There were 206 rectal shaves (90.4%), 2 disc resections (0.9%), and 20 segmental bowel resections (8.8%). A multivariable analysis demonstrated an association between bowel resection and ≥2 nodules located in the rectovaginal space (odds ratio [OR] 6.85; 95% confidence interval [CI], 1.37-34.2), nodules in the vesicouterine pouch (OR 5.87; 95% CI, 1.03-33.3), and increasing nodule size (OR 2.39 per 1 cm increase per 1 cm diameter increase; 95% CI, 1.56-3.64). CONCLUSION: Ultrasound findings of endometriotic nodule location, number of nodules, and increasing size are independent predictors of segmental bowel resection at the time of surgery for rectovaginal endometriosis. This highlights the importance of accurate diagnostic evaluation to aid counseling and surgical planning in the preoperative setting for women with rectovaginal endometriosis.

New insights into the etiopathology of placenta accreta spectrum.

Placenta accreta has been described as a spectrum of abnormal attachment of villous tissue to the uterine wall, ranging from superficial attachment to the inner myometrium without interposing decidua to transmural invasion through the entire uterine wall and beyond. These descriptions have prevailed for more than 50 years and form the basis for the diagnosis and grading of accreta placentation. Accreta placentation is essentially the consequence of uterine remodeling after surgery, primarily after cesarean delivery. Large cesarean scar defects in the lower uterine segment are associated with failure of normal decidualization and loss of the subdecidual myometrium. These changes allow the placental anchoring villi to implant, and extravillous trophoblast cells to migrate, close to the serosal surface of the uterus. These microscopic features are central to the misconception that the accreta placental villous tissue is excessively invasive and have led to much confusion and heterogeneity in clinical data. Progressive recruitment of large arteries in the uterine wall, that is, helicine, arcuate, and/or radial arteries, results in high-velocity maternal blood entering the intervillous space from the first trimester of pregnancy and subsequent formation of placental lacunae. Recently, guided sampling of accreta areas at delivery has enabled accurate correlation of prenatal imaging data with intraoperative features and histopathologic findings. In more than 70% of samples, there were thick fibrinoid depositions between the tip of most anchoring villi and the underlying uterine wall and around all deeply implanted villi. The distortion of the uteroplacental interface by these dense depositions and the loss of the normal plane of separation are the main factors leading to abnormal placental attachment. These data challenged the classical concept that placenta accreta is simply owing to villous tissue sitting atop the superficial myometrium without interposed decidua. Moreover, there is no evidence in accreta placentation that the extravillous trophoblast is abnormally invasive or that villous tissue can cross the uterine serosa into the pelvis. It is the size of the scar defect, the amount of placental tissue developing inside the scar, and the residual myometrial thickness in the scar area that determine the distance between the placental basal plate and the uterine serosa and thus the risk of accreta placentation.

An observational cohort study of health outcomes and costs associated with early pregnancy assessment units in the UK.

BACKGROUND: The objective of this study was to assess the impact of consultant presence, volume of patients seen and weekend opening on the health and cost-related outcomes associated with different Early Pregnancy Assessment Unit (EPAU) configurations. METHODS: This was an observational study with a prospective cohort design. Six thousand six hundred six pregnant women (16 years of age and over) attending EPAUs because of suspected early pregnancy complications were recruited from 44 EPAUs across the UK. The main outcome measures were quality of life, costs, and anxiety. RESULTS: Costs, quality of life and anxiety scores were similar across configurations with little evidence to suggest an impact of consultant presence, weekend opening or volume of patients seen. Mean overall costs varied from £92 (95% CI £85 - £98) for a diagnosis of normally developing pregnancy to £1793 (95% CI £1346 - £2240) for a molar pregnancy. EQ-5D-5L score increased from 0.85 (95% CI 0.84-0.86) at baseline to 0.91 (95% CI 0.90-0.92) at 4 weeks for the 573 women who completed questionnaires at both time points, largely due to improvements in the pain/discomfort and anxiety/depression dimensions. 78% of women reported a decrease in their anxiety score immediately following their EPAU appointment. CONCLUSIONS: EPAU configuration, as specified in this study, had limited impact on any of the outcomes examined. However, it is clear that care provided in the EPAU has a positive overall effect on women's health and emotional wellbeing, with significant improvements in EQ-5D and anxiety shown following an EPAU visit.

A prospective comparison of the diagnostic accuracies of ultrasound and magnetic resonance imaging in preoperative staging of endometrial cancer.

OBJECTIVE: To compare the diagnostic accuracies of ultrasound and magnetic resonance imaging (MRI) for deep (≥50%) myometrial invasion (DMI) and cervical stromal invasion (CSI) in women with endometrial cancer. METHODS: This was a prospective study at a gynecology clinic for women with postmenopausal bleeding. Between October 2015-October 2018, consecutive women with suspected endometrial cancer based on ultrasound subjective pattern recognition were simultaneously assessed for DMI and CSI on ultrasound. Subsequently, they also underwent preoperative MRI. We compared the diagnostic accuracies of ultrasound and MRI in predicting DMI and CSI with the final histology as the gold standard. RESULTS: We included 51 women. The prevalence of DMI and CSI were 22/51 (43%) and 7/51 (14%), respectively. The majority of malignancies were of endometrioid histological subtype (38/51, 75%) and FIGO stage 1 or 2 (40/51, 78%). Ultrasound diagnosed more cases of DMI compared to MRI (19/22 vs. 17/22), however, the difference was not statistically significant. The sensitivities and specificities of ultrasound and MRI for DMI were 86% vs. 77% and 66% vs. 76%, respectively. For CSI, ultrasound and MRI correctly diagnosed the same number of cases (5/7, 71%); their respective false-positive rates were low, 0/44 (0%) and 1/44 (2%). Ultrasound and MRI had a moderate agreement for DMI (ƙ=0.49; 95% confidence interval [CI]=0.26-0.73), whereas the agreement for CSI was substantial (ƙ=0.69; 95% CI=0.36-1.00). CONCLUSION: Endometrial cancer can be simultaneously diagnosed and staged at women's initial ultrasound assessment. The accuracies of ultrasound for DMI and CSI are comparable to MRI. TRIAL REGISTRATION: ISRCTN Identifier: ISRCTN24363390.

Risk of Pre-Malignancy or Malignancy in Postmenopausal Endometrial Polyps: A CHAID Decision Tree Analysis.

BACKGROUND AND AIMS: Postmenopausal endometrial polyps are commonly managed by surgical resection; however, expectant management may be considered for some women due to the presence of medical co-morbidities, failed hysteroscopies or patient's preference. This study aimed to identify patient characteristics and ultrasound morphological features of polyps that could aid in the prediction of underlying pre-malignancy or malignancy in postmenopausal polyps. METHODS: Women with consecutive postmenopausal polyps diagnosed on ultrasound and removed surgically were recruited between October 2015 to October 2018 prospectively. Polyps were defined on ultrasound as focal lesions with a regular outline, surrounded by normal endometrium. On Doppler examination, there was either a single feeder vessel or no detectable vascularity. Polyps were classified histologically as benign (including hyperplasia without atypia), pre-malignant (atypical hyperplasia), or malignant. A Chi-squared automatic interaction detection (CHAID) decision tree analysis was performed with a range of demographic, clinical, and ultrasound variables as independent, and the presence of pre-malignancy or malignancy in polyps as dependent variables. A 10-fold cross-validation method was used to estimate the model's misclassification risk. RESULTS: There were 240 women included, 181 of whom presented with postmenopausal bleeding. Their median age was 60 (range of 45-94); 18/240 (7.5%) women were diagnosed with pre-malignant or malignant polyps. In our decision tree model, the polyp mean diameter (≤13 mm or >13 mm) on ultrasound was the most important predictor of pre-malignancy or malignancy. If the tree was allowed to grow, the patient's body mass index (BMI) and cystic/solid appearance of the polyp classified women further into low-risk (≤5%), intermediate-risk (>5%-≤20%), or high-risk (>20%) groups. CONCLUSIONS: Our decision tree model may serve as a guide to counsel women on the benefits and risks of surgery for postmenopausal endometrial polyps. It may also assist clinicians in prioritizing women for surgery according to their risk of malignancy.

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.

Diagnosis and outcome of hydatidiform moles in missed-miscarriage: a cohort-study, systematic review and meta-analysis.

OBJECTIVE: To evaluate the ultrasound diagnostic rates of complete hydatidiform moles (CHM) and partial hydatidiform moles (PHM) in women presenting with a missed miscarriage, the clinical complications at diagnosis and the risk of gestational trophoblastic neoplasia (GTN) after surgical evacuation and to compare our findings with those of the published literature by completing a systematic review and meta-analysis STUDY DESIGN: Retrospective review of the data of 295 women diagnosed with a histologically confirmed hydatidiform moles (HM) over a 15-year period, including 128 CHM and 167 PHM. All women were referred to a regional specialist centre for follow-up and further management. An electronic search of PubMed, Google Scholar and MEDLINE was performed for studies published between September 1973 and September 2017 reporting on the early ultrasound diagnosis of hydatidiform mole. Only cohort studies which provided ultrasound data confirmed by histopathology were included. RESULTS: In the cohort study, ultrasound imaging diagnosed a significantly (p < 0.001) higher number of CHM (95/128 (74.2%) than PHM (68/167 (40.7%). Ovarian theca lutea cysts were observed in three CHM and one PHM. There were no cases of pre-eclampsia or thyrotoxicosis at the time of diagnosis. Maternal serum ß-human chorionic gonadotrophin levels were abnormally low (< 0.5 MoM) in 5/51 (10%) CHM and 23/43 (53%) PHM and abnormally high (> 2.0 MoM) in 20/51 (39%) CHM and 2/43 (5%) PHM. Seventeen (12.3%) CHM and two (1.4%) PHM developed a GTN requiring treatment. In the literature the proportion of histologically diagnosed HM, suspected on ultrasound in early pregnancy, ranged between 34.2 and 90.2% for HM, 57.8 and 95% for CHM and 17.6 and 51.6% for PHM. The meta-analysis indicated substantial heterogeneity in the overall ultrasound diagnosis of HM and in the differential diagnosis between CHM and PHM. CONCLUSION(S): As around a third of CHM and two thirds of PHM are not diagnosed on ultrasound in cases of missed miscarriage, histopathological examination of all products of conception in case of early pregnancy failure is essential to detect molar changes. This is particularly important for the management of women with CHM who have a higher risk of developing a GTN.

Ultrasound diagnosis of complete and partial hydatidiform moles in early pregnancy failure: An inter-observer study.

We evaluated the accuracy of the ultrasound signs suggestive of complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) in a cohort of women with histologically confirmed hydatidiform mole (HM) who presented with early pregnancy failure, including 103 CHM and 95 PHM for which ultrasound images were available. The accuracy of the differential diagnosis was significantly (p < 0.001) greater during secondary examination of ultrasound images compared with the original primary ultrasound examination. The interobserver agreement analysis indicated only a fair to moderate agreement between the two examinations (kappa value 0.41; 95% CI 0.29-0.53). Most HM present as early pregnancy failure and identification of early ultrasound signs can improve the differential diagnosis between CHM and PHM.

The prevalence of incidental uterine venous plexus thrombosis in women attending a gynecology clinic.

BACKGROUND: The uterine venous plexus (UVP) is an unusual site for venous thrombosis (VT). Our aim was to determine the prevalence of UVP thrombosis (UVPT) and identify associated risk factors. METHODS: We conducted a cross-sectional study on consecutive nonpregnant women attending our general gynecology clinic with a wide variety of presenting symptoms over a 16-month period. All women underwent a transvaginal ultrasound scan which involved detailed examination of the uterine venous plexus. Women diagnosed with incidental UVPT had thrombophilia screening, lower limb venous duplex imaging, and specialist hematological review. Logistic regression was used to examine associations between various risk factors and UVPT. RESULTS: We screened 1383 women, 39 of whom had an incidental UVPT, giving a prevalence of 3.0% (95% confidence interval [CI], 2.1%-4.1%). Multivariate analysis showed positive associations between multiparity (odds ratio [OR] 5.75 [95% CI 2.10, 15.7]), recent surgery (OR 3.10 [95% CI 1.19, 8.07]), presence of leg varicose veins (OR 3.15 [95% CI 1.32, 7.49]), and a family history of venous thromboembolism (OR 8.74 [1.65, 46.4]) and negative associations between postmenopausal status (OR 0.36 [95% CI 0.13, 0.95]) and the development of UVPT. Thrombophilia was detected in 12.8% women diagnosed with UVPT. CONCLUSIONS: The prevalence of incidental UVPT in a general gynecology population was 3.0%. Several demographic and clinical factors were found to be associated with UVPT. This could help to identify women at risk of this condition, and facilitate its early detection and development of evidence-based management strategies.

Progesterone to prevent miscarriage in women with early pregnancy bleeding: the PRISM RCT.

BACKGROUND: Progesterone is essential for a healthy pregnancy. Several small trials have suggested that progesterone therapy may rescue a pregnancy in women with early pregnancy bleeding, which is a symptom that is strongly associated with miscarriage. OBJECTIVES: (1) To assess the effects of vaginal micronised progesterone in women with vaginal bleeding in the first 12 weeks of pregnancy. (2) To evaluate the cost-effectiveness of progesterone in women with early pregnancy bleeding. DESIGN: A multicentre, double-blind, placebo-controlled, randomised trial of progesterone in women with early pregnancy vaginal bleeding. SETTING: A total of 48 hospitals in the UK. PARTICIPANTS: Women aged 16-39 years with early pregnancy bleeding. INTERVENTIONS: Women aged 16-39 years were randomly assigned to receive twice-daily vaginal suppositories containing either 400 mg of progesterone or a matched placebo from presentation to 16 weeks of gestation. MAIN OUTCOME MEASURES: The primary outcome was live birth at ≥ 34 weeks. In addition, a within-trial cost-effectiveness analysis was conducted from an NHS and NHS/Personal Social Services perspective. RESULTS: A total of 4153 women from 48 hospitals in the UK received either progesterone (n = 2079) or placebo (n = 2074). The follow-up rate for the primary outcome was 97.2% (4038 out of 4153 participants). The live birth rate was 75% (1513 out of 2025 participants) in the progesterone group and 72% (1459 out of 2013 participants) in the placebo group (relative rate 1.03, 95% confidence interval 1.00 to 1.07; p = 0.08). A significant subgroup effect (interaction test p = 0.007) was identified for prespecified subgroups by the number of previous miscarriages: none (74% in the progesterone group vs. 75% in the placebo group; relative rate 0.99, 95% confidence interval 0.95 to 1.04; p = 0.72); one or two (76% in the progesterone group vs. 72% in the placebo group; relative rate 1.05, 95% confidence interval 1.00 to 1.12; p = 0.07); and three or more (72% in the progesterone group vs. 57% in the placebo group; relative rate 1.28, 95% confidence interval 1.08 to 1.51; p = 0.004). A significant post hoc subgroup effect (interaction test p = 0.01) was identified in the subgroup of participants with early pregnancy bleeding and any number of previous miscarriage(s) (75% in the progesterone group vs. 70% in the placebo group; relative rate 1.09, 95% confidence interval 1.03 to 1.15; p = 0.003). There were no significant differences in the rate of adverse events between the groups. The results of the health economics analysis show that progesterone was more costly than placebo (£7655 vs. £7572), with a mean cost difference of £83 (adjusted mean difference £76, 95% confidence interval -£559 to £711) between the two arms. Thus, the incremental cost-effectiveness ratio of progesterone compared with placebo was estimated as £3305 per additional live birth at ≥ 34 weeks of gestation. CONCLUSIONS: Progesterone therapy in the first trimester of pregnancy did not result in a significantly higher rate of live births among women with threatened miscarriage overall, but an important subgroup effect was identified. A conclusion on the cost-effectiveness of the PRISM trial would depend on the amount that society is willing to pay to increase the chances of an additional live birth at ≥ 34 weeks. For future work, we plan to conduct an individual participant data meta-analysis using all existing data sets. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14163439, EudraCT 2014-002348-42 and Integrated Research Application System (IRAS) 158326. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 33. See the NIHR Journals Library website for further project information.

Miscarriage is a common complication of pregnancy that affects one in five pregnancies. Several small studies have suggested that progesterone, a hormone essential for maintaining a pregnancy, may reduce the risk of miscarriage in women presenting with early pregnancy bleeding. This research was undertaken to test whether or not progesterone given to pregnant women with early pregnancy bleeding would increase the number of live births when compared with placebo (dummy treatment). The women participating in the study had an equal chance of receiving progesterone or placebo, as determined by a computer; one group received progesterone (400 mg twice daily as vaginal pessaries) and the other group received placebo with an identical appearance. Treatment began when women presented with vaginal bleeding, were < 12 weeks of gestation and were found to have at least a pregnancy sac on an ultrasound scan. Treatment was stopped at 16 weeks of gestation, or earlier if the pregnancy ended before 16 weeks. Neither the participants nor their health-care professionals knew which treatment was being received. In total, 23,775 women were screened and 4153 women were randomised to receive either progesterone or placebo pessaries. Altogether, 2972 participants had a live birth after at least 34 weeks of gestation. Overall, the live birth rate in the progesterone group was 75% (1513 out of 2025 participants), compared with 72% (1459 out of 2013 participants) in the placebo group. Although the live birth rate was 3% higher in the progesterone group than in the placebo group, there was statistical uncertainty about this finding. However, it was observed that women with a history of one or more previous miscarriages and vaginal bleeding in their current pregnancy may benefit from progesterone. For women with no previous miscarriages, our analysis showed that the live birth rate was 74% (824 out of 1111 participants) in the progesterone group compared with 75% (840 out of 1127 participants) in the placebo group. For women with one or more previous miscarriages, the live birth rate was 75% (689 out of 914 participants) in the progesterone group compared with 70% (619 out of 886 participants) in the placebo group. The potential benefit appeared to be most strong for women with three or more previous miscarriages, who had a live birth rate of 72% (98 out of 137 participants) in the progesterone group compared with 57% (85 out of 148 participants) in the placebo group. Treatment with progesterone did not appear to have any negative effects.