Maternal serum markers in predicting successful outcome in expectant management of missed miscarriage

The aim of this study was to evaluate the use of biological serum markers, available routinely in most hospital clinical laboratories, in predicting successful outcomes of expectant management in women presenting with a missed miscarriage. This is a single centre observational prospective study over a 16-month period. Among the 490 women who consented to the study protocol, 83 presented with missed miscarriage during the first trimester of pregnancy and opted for expectant management. The mean gestation sac diameter and volume of the gestation sac were recorded during ultrasound examination. Maternal serum samples were obtained in each case and assayed for human chorionic gonadotrophin, progesterone, pregnancy associated plasma protein A (PAPP-A) and high-sensitivity C-reactive protein using commercial assays. When examined individually, maternal age (P = 0.01), progesterone (P = 0.03) and PAPP-A (P = 0.02) were all significantly associated with successful expectant management. Increased maternal age was associated with an increased chance of success with the odds of success increased by around 75% for a 5-year increase in age. Higher values of progesterone and PAPP-A were associated with a reduced chance of successful management. Low maternal serum progesterone concentration was the strongest parameter associated with a successful spontaneous completion of miscarriage

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

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

New insights in the pathophysiology of complete hydatidiform mole

OBJECTIVE: The majority of complete hydatidiform moles (CHM) are detected on ultrasound examination by the end of the first trimester when they present as multiple sonolucent cysts. To better understand the pathophysiology of this unique placental pathology and improve its prenatal diagnosis and management we have reviewed the ultrasound features of CHM before the appearance of cystic changes. STUDY DESIGN: We searched our database to identify all women diagnosed with a complete hydatidiform mole confirmed by histopathology who had an ultrasound examination before 9 weeks' gestation. We reviewed their ultrasound reports and all the corresponding images. RESULTS: The study group included 39 women with a positive pregnancy test and vaginal bleeding, 36 of whom had at least two ultrasound examinations before 9 weeks' gestation. At the first scan (mean gestation age 7 + 1 weeks; SD 1.1), 29 out 39 (74.4%) of CHM presented as a heterogeneous hyperechogenic mass with or without gestational sac and the remaining ten (25.6%) cases as a regular 4-week gestational sac. Cystic molar changes became apparent from the end of the second month of gestation. CONCLUSION: The development of a CHM follows a well-defined pattern starting with a macroscopically normal gestation sac at 4 weeks, which transforms into a polypoid mass between 5 and 7 weeks of gestation. The hydropic changes of the villous tissue is progressive and rarely visible in utero on ultrasound before 8 weeks of gestation. These findings should allow an earlier diagnosis and assist in the management counselling of women with CHM

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

Emotional experiences of women who access early pregnancy assessment units: a qualitative investigation

Purpose: Early pregnancy complications are common and often result in pregnancy loss, which can be emotionally challenging for women. Research on the emotional experiences of those attending Early Pregnancy Assessment Units [EPAUs] is scarce. This analysis explored the emotions which women spontaneously reported when being interviewed about their experiences of using EPAU services. Materials and methods: Semi-structured telephone interviews were conducted with a purposive sample of 38 women. Using Thematic Framework Analysis, we identified six unique emotional typologies which mapped onto women’s clinical journeys. Results: Women with ongoing pregnancies were characterized as having: “Anxious Presentation” or “Sustained Anxiety due to Diagnostic Uncertainty”, dependent on whether their initial scan result was inconclusive. Women with pregnancy loss had one of four emotional typologies, varying by diagnostic timing and required interventions: “Anxious-Upset”; “Anxious-Upset after Diagnostic Uncertainty”; “Anxious-Upset with Procedural Uncertainty”; “Anxious with Sustained Uncertainty”. Conclusions: We provide insights into the distinct emotions associated with different clinical pathways through EPAU services. Our findings could be used to facilitate wider recognition of women’s emotional journeys through early pregnancy complications and stimulate research into how best to support women and their partners, in these difficult times

Women's experiences of early pregnancy assessment unit services: a qualitative investigation

Objective: To explore the experiences of women who had used an Early Pregnancy Assessment Unit (EPAU) service in the UK and make recommendations for their improvement. Design: Qualitative interview study. Setting: Early Pregnancy Assessment Units in the UK. Sample: A maximum variation sample of women who had consented to be interviewed having attended one of 26 EPAUs involved in the VESPA study in 2018. Methods: In-depth telephone interviews with 38 women. A thematic framework analysis was conducted, with a focus on how experiences varied according to EPAU service configuration and clinical pathway. Main outcome measures: Women's experiences of EPAU services. Results: We found that EPAUs are highly valued, and women's experiences were generally positive. However, women reported a range of issues that negatively affected their experience. These included difficulties accessing the service, insensitive management of the investigation and treatment options of pregnancy loss, poor communication, insufficient information and a lack of support for their psychological health. These issues were not strongly associated with EPAU configuration or clinical pathway. Conclusions: Recommendations to improve women's experiences include the separation of EPAUs from general maternity services, and we make suggestions on how to remove barriers to access by reviewing opening hours, how to provide sensitive patient management, such as automatically cancelling appointments and scans following pregnancy loss, and how to improve communication, both with women and their partners as well as with other parts of the health service. Tweetable abstract: Early Pregnancy Assessment Units are highly valued by women but aspects of their care experiences, particularly around sensitive management of pregnancy loss, could be improved

Women’s experiences of early pregnancy loss services during the pandemic: A qualitative investigation

Problem Early pregnancy losses [EPL] are common, varied, and require different courses of management and care. Background In the UK, women who suspect or suffer a pregnancy loss are usually provided specialist care in early pregnancy assessment units [EPAUs]. Their configuration has recently been evaluated, but recommendations for change in-line with best practice for optimum outcomes were unable to be implemented due to the COVID-19 pandemic health system shock. Aim To compare women’s experiences of EPAUs during the pandemic to themes previously found in qualitative work undertaken with women who utilised EPAUs before the pandemic. Methods We conducted semi-structured virtual interviews, with women (N = 32) who suffered an early pregnancy loss during the pandemic; analysing transcripts using Template Analysis, based on findings about women’s (pre-pandemic) experiences of EPAU from The VESPA Study. Findings We report on seven key themes: Barriers to Accessing Services; Communication & Information; Retention of Relational Care; Involvement in Care Decisions; Staffs’ Attitude or Approach; Efficiency of Service Delivery; Sensitive Patient Management. Discussion Sensitive patient management and woman-staff interactions in EPAU settings remain a fundamental issue. Women also reported their experiences of EPAUs were comparatively worse during the pandemic. Conclusions Women valued the care provided by EPAUs and found services to be efficient, despite pandemic-related restrictions. However, psychological recognition surrounding EPL and appropriate, sensitive, relational care and support continue to be areas in need of improvement. Our recommendation is to implement the improvements suggested by VESPA as a priority to ameliorate present sub-optimal experiences and prevent further deterioration. Abbreviations NHS National Health Service PPIE Patient and Public Involvement and Engagement SARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2 (a.k.a. COVID-19) UK United Kingdo

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

Differences in the organisation of early pregnancy units and the effect of senior clinician presence, volume of patients and weekend opening on emergency hospital admissions: Findings from the VESPA Study

Objective To determine whether the participation of consultant gynaecologists in delivering early pregnancy care results in a lower rate of acute hospital admissions. Design Prospective cohort study and emergency hospital care audit; data were collected as part of the national prospective mixed-methods VESPA study on the "Variations in the organization of EPAUs in the UK and their effects on clinical, Service and PAtient-centred outcomes". Setting 44 Early Pregnancy Assessment Units (EPAUs) across the UK randomly selected in balanced numbers from eight pre-defined mutually exclusive strata. Participants 6606 pregnant women (≥16 years old) with suspected first trimester pregnancy complications attending the participating EPAUs or Emergency Departments (ED) from December 2016 to July 2017. Exposures Planned and actual senior clinician presence, unit size, and weekend opening. Main outcome measures Unplanned admissions to hospital following any visit for investigations or treatment for first trimester complications as a proportion of women attending EPAUs. Results 205/6397 (3.2%; 95% CI 2.8-3.7) women were admitted following their EPAU attendance. The admission rate among 44 units ranged from 0% to 13.7% (median 2.8). Neither planned senior clinician presence (p = 0.874) nor unit volume (p = 0.247) were associated with lower admission rates from EPAU, whilst EPAU opening over the weekend resulted in lower admission rates (p = 0.027). 1445/5464 (26.4%; 95%CI 25.3 to 27.6) women were admitted from ED. There was little evidence of an association with planned senior clinician time (p = 0.280) or unit volume (p = 0.647). Keeping an EPAU open over the weekend for an additional hour was associated with 2.4% (95% CI 0.1% to 4.7%) lower odds of an emergency admission from ED. Conclusions Involvement of senior clinicians in delivering early pregnancy care has no significant impact on emergency hospital admissions for early pregnancy complications. Weekend opening, however, may be an effective way of reducing emergency admissions from ED