Bleeding and pain are experienced by 20% of women during the first trimester of pregnancy. Although most pregnancies complicated by pain and bleeding tend to progress normally, these symptoms are ...distressing for woman, and they are also associated with an increased risk of miscarriage and ectopic pregnancy. Ultrasound is the first and often the only diagnostic modality that is used to determine location of early pregnancy and to assess its health. Ultrasound is an accurate, safe, painless and relatively inexpensive diagnostic tool, which all contributed to its widespread use in early pregnancy. Pain and bleeding in early pregnancy are sometimes caused by concomitant gynaecological, gastrointestinal, and urological problems, which could also be detected on ultrasound scan. In women with suspected intra-abdominal bleeding, ultrasound scan can be used to detect the presence of blood and provide information about the extent of bleeding. In this chapter, we comprehensively review the use of ultrasound in the diagnosis and management of early pregnancy complications. We include information about the diagnosis of gynaecological and other pelvic abnormalities, which could cause pain or bleeding in pregnancy. We also provide a summary of the current views on the safety of ultrasound in early pregnancy.
To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies.
Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed ...on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative.
Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006).
We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management.
Serum β hCG level.
Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05).
We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
To develop and implement a core outcome set to guide future research in ectopic pregnancy.
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.
COMET 1492 . Registered in November 2019.
Summary Background The diagnostic accuracy of ultrasonography for differentiating between benign and malignant adnexal masses is proportional to the expertise of the operator. However, we do not know ...whether improved diagnostic accuracy will affect the management of these tumours. We assessed the effect of the quality of gynaecological ultrasonography on the management of patients with suspected ovarian cancer in a randomised controlled trial. Methods 165 patients who were referred to the regional gynaecological cancer centre at Guy's and St Thomas' NHS Foundation Trust (London, UK), between June 7, 2004, and April 23, 2006, with suspected adnexal tumours met the inclusion criteria. Of these, 150 patients were randomly assigned to either level II (routine) ultrasonography (n=73) or to level III (expert) ultrasonography (n=77). The primary endpoint was the number of major surgical staging procedures (including a laparotomy and at least an oophorectomy and omental biopsy) in each group of the study. Secondary endpoints were: total number of surgical procedures; number of minimally invasive procedures (eg, operative laparoscopy or ultrasonography-guided cyst aspiration); number of additional diagnostic tests (eg, CT or laparoscopy); number of follow-up scans; diagnostic accuracy of level II and level III ultrasonography; and duration of hospital stay. All analyses were by intention to treat. This study is registered on the Current Controlled Trials website http://www.controlled-trials.com/mrct/trial/230201/ISRCTN02631195. Findings More major surgical staging procedures for suspected ovarian cancer were done in the level II group than in the level III group of the study (27 of 73 37% vs 17 of 77 22%, respectively; difference between groups 15% 95% CI 0–29; RR 1·68 1·00–2·81; p=0·049). The total number of surgical procedures was similar between the two groups: 35 of 73 (48%) in the level II group and 33 of 77 (43%) in the level III group (RR 1·12 0·79–1·59; p=0·53). The median duration of hospital stay for patients who were operated on was 6 days (range 3–13) in the level II group and 5 days (range 1–9) in the level III group (p=0·01). A likely histological diagnosis was provided to clinicians after ultrasonography for 76 of 77 (99%) patients in the level III group compared with only 38 of 73 (52%) patients in the level II group. 18 of 150 (12%) patients recruited were eventually diagnosed with ovarian malignancy. The sensitivity and specificity of ultrasonography was 2 of 5 (40%; 95% CI 6·5–84·6) and 10 of 10 (100%; 34–100), respectively, in the level II group and 7 of 8 (88%; 47–98) and 27 of 28 (96%; 82–99), respectively, in the level III group. Interpretation Improved quality of ultrasonography has a measurable effect on the management of patients with suspected ovarian cancer in a tertiary gynaecology cancer centre, and results in a significant decrease in the number of major staging procedures and a shorter inpatient hospital stay.
The management of incidental or unusual site venous thrombosis (VT) is challenging and is often extrapolated from studies on symptomatic deep venous thrombosis (DVT). There is a tendency to treat ...with anticoagulation, due to the theoretical risk of propagation and embolism; however, this is not without risk. Furthermore, there is little guidance on how to monitor incidental VT. The aim of this study was to describe the natural history of incidental uterine venous plexus thrombosis (UVPT) and provide a structured approach to its overall management. A prospective study was conducted in a university teaching hospital over a 16-month period. Women diagnosed with UVPT on transvaginal ultrasound (TVS) were followed up over a six-month period and managed based on an individualised risk assessments, in conjunction with haematologists. Fifty women were diagnosed with UVPT during the study period, of which 38 were managed expectantly. The resolution was documented in 70% of women. There were no cases of symptomatic DVT or pulmonary embolisms in either the expectant or treatment groups. Our study has shown that in a high proportion of women, incidental UVPT could be managed successfully without the need for anticoagulation. The overall management of UVPT should be based on individualised clinical risk assessments.
To test the value of serum CA-125 measurements alone or as part of a multimodal strategy to distinguish between malignant and benign ovarian tumors before surgery based on a large prospective ...multicenter study (International Ovarian Tumor Analysis).
Patients with at least one persistent ovarian mass preoperatively underwent transvaginal ultrasonography using gray scale imaging to assess tumor morphology and color Doppler imaging to obtain indices of blood flow.
Data from 809 patients recruited from nine centers were included in the analysis; 567 patients (70%) had benign tumors and 242 (30%) had malignant tumors-of these 152 were primary invasive (62.8%), 52 were borderline malignant (21.5%), and 38 were metastatic (15.7%). A logistic regression model including CA-125 (M2) resulted in an area under the receiver operating characteristic curve (AUC) of 0.934 and did not outperform a published (M1) without serum CA-125 information (AUC, 0.936). Specifically designed new models including CA-125 for premenopausal women (M3) and for postmenopausal women (M4) did not perform significantly better than the model without CA-125 (M1; AUC, 0.891 v AUC, 0.911 and AUC, 0.975 v AUC, 0.949, respectively). In postmenopausal patients, serum CA-125 alone (AUC, 0.920) and the risk of malignancy index (AUC, 0.924) performed very well. Results were very similar when the models were prospectively tested on a group of 345 new patients with adnexal masses of whom 126 had malignant tumors (37%).
Adding information on CA-125 to clinical information and ultrasound information does not improve discrimination of mathematical models between benign and malignant adnexal masses.
Background
Tubal ectopic pregnancies can cause significant morbidity or even death. Current treatment is with methotrexate or surgery. However, methotrexate treatment can fail in approximately 30% of ...women. Gefitinib, an epidermal growth factor receptor inhibitor, may improve the effects of methotrexate. We assessed the efficacy of administering oral gefitinib with methotrexate, versus methotrexate alone, to treat a tubal ectopic pregnancy.
Objectives
To test the hypothesis a combination of gefitinib with methotrexate can increase resolution of stable tubal ectopic pregnancy without the need for surgery, compared with methotrexate alone.
Design
A randomised, double-blind, placebo-controlled, multicentre, superiority trial.
Setting
Fifty UK hospitals.
Participants
A target of 328 women with a stable, tubal ectopic pregnancy.
Intervention
Women were randomised to combination of methotrexate and gefitinib or methotrexate and placebo. All participants received a single intramuscular dose of methotrexate 50 mg/m
2
and were randomised in a 1:1 ratio of oral gefitinib (250 mg daily for 7 days) or placebo.
Main outcome measures
The primary outcome was surgical intervention for resolution of ectopic pregnancy. Secondary outcomes were the need for an additional dose of methotrexate, time to resolution of the ectopic pregnancy, number of treatment-associated hospital visits, safety and tolerability, acceptability of treatment and return to menses.
Results
Between 2 November 2016 and 6 October 2021, 328 women were randomly allocated to methotrexate and gefitinib (
n
= 165) or methotrexate and placebo (
n
= 163). Three women in the placebo group withdrew. Surgical intervention occurred in 30% (50/165) of the gefitinib group and in 29% (47/160) of the placebo group (adjusted risk ratio 1.15, 95% confidence interval 0.85 to 1.58; adjusted risk difference −0.01, 95% confidence interval −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% confidence interval 0.75 to 1.40). The need for additional methotrexate doses, number of additional hospital visits, participant acceptability, time to return of menses and serious adverse events were similar in both groups. Diarrhoea and rash were more common in the gefitinib group.
Conclusions
The addition of gefitinib to standard medical management with methotrexate to treat tubal ectopic pregnancy is not clinically effective as it does not reduce subsequent surgical intervention and is associated with higher rates of reported symptoms than placebo.
Limitations
We were unable to investigate how different gefitinib doses or modes of delivery would impact on the results.
Future work
Questions that remain unaddressed relate to the use of methotrexate and gefitinib combination treatment for other extrauterine and uterine ectopic pregnancy, such as caesarean scar pregnancies, or in the management of choriocarcinoma.
Trial registration
This trial is registered as ISRCTN 67795930 and EudraCT 2015-005013-76.
Funding
This project was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme and will be published in full in
Efficacy and Mechanistic Evaluation
; Vol. 10, No. 1. The gefitinib and placebo were supplied by Astra Zeneca. See the NIHR Journals Library website for further project information.
Tubal ectopic pregnancy (tEP) is the most common life-threatening condition in gynaecology. Treatment options include surgery and medical management. Stable women with tEPs with pre-treatment serum ...human chorionic gonadotrophin (hCG) levels < 1000 IU/L respond well to outpatient medical treatment with intramuscular methotrexate. However, tEPs with hCG > 1000 IU/L can take significant time to resolve with methotrexate and require multiple outpatient monitoring visits. In pre-clinical studies, we found that tEP implantation sites express high levels of epidermal growth factor receptor. In early-phase trials, we found that combination therapy with gefitinib, an orally active epidermal growth factor receptor antagonist, and methotrexate resolved tEPs without the need for surgery in over 70% of cases, did not cause significant toxicities, and was well tolerated. We describe the protocol of a randomised trial to assess the efficacy of combination gefitinib and methotrexate, versus methotrexate alone, in reducing the need for surgical intervention for tEPs.
We propose to undertake a multi-centre, double-blind, placebo-controlled, randomised trial (around 70 sites across the UK) and recruit 328 women with tEPs (with pre-treatment serum hCG of 1000-5000 IU/L). Women will be randomised in a 1:1 ratio by a secure online system to receive a single dose of intramuscular methotrexate (50 mg/m
) and either oral gefitinib or matched placebo (250 mg) daily for 7 days. Participants and healthcare providers will remain blinded to treatment allocation throughout the trial. The primary outcome is the need for surgical intervention for tEP. Secondary outcomes are the need for further methotrexate treatment, time to resolution of the tEP (serum hCG ≤ 15 IU/L), number of hospital visits associated with treatment (until resolution or scheduled/emergency surgery), and the return of menses by 3 months after resolution. We will also assess adverse events and reactions until day of resolution or surgery, and participant-reported acceptability at 3 months.
A medical intervention that reduces the need for surgery and resolves tEP faster would be a favourable treatment alternative. If effective, we believe that gefitinib and methotrexate could become standard care for stable tEPs.
ISRCTN Registry ISRCTN67795930 . Registered 15 September 2016.
Effect of cesarean delivery on the endometrium Ben-Nagi, Jara; Walker, Amy; Jurkovic, Davor ...
International journal of gynecology and obstetrics,
July 2009, Letnik:
106, Številka:
1
Journal Article
Recenzirano
Abstract Objective To compare endometrial tissue samples from cesarean scar (CS) sites and from the posterior uterine wall to better understand the pathophysiology of implantation into a CS. Methods ...Endometrial samples were taken from both a CS site and the posterior wall in premenopausal women with CSs, and from the posterior wall in premenopausal women who had spontaneous vaginal deliveries (SVDs) only. Results In the secretory phase, there were significantly fewer leukocytes at CS sites than in the endometrium of women who had SVDs only ( P < 0.05). Significant differences in leukocytic infiltration and cell proliferation between the proliferative and secretory phases were only found in women who had SVDs only ( P < 0.05). Conclusion Leukocyte recruitment to the endometrium during the secretory phase may be affected by the presence of a CS.
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