Predicting Pouch of Douglas Obliteration Using Ultrasound and Laparoscopic Video Sets: An Interobserver and Diagnostic Accuracy Study.

OBJECTIVES: To investigate the diagnostic accuracy and interobserver agreement among sonologists when assessing offline ultrasound (US) video sets of the "sliding sign" and among gynecologic surgeons when assessing corresponding laparoscopic video sets to predict pouch of Douglas (POD) obliteration and to compare the performance of the groups. METHODS: A diagnostic and reproducibility study was conducted, including 15 observers in 4 groups: (1) senior sonologists, (2) junior sonologists, (3) general gynecologists, and (4) advanced laparoscopists. The sonologists viewed 25 offline preoperative US video sets of the sliding sign, and the surgeons viewed the corresponding intraoperative laparoscopic videos of the same patients. Each observer was asked to classify POD obliteration in the video sets and was compared to the reference standard POD state determined at real-time laparoscopy by a single investigator (G.C.). The interobserver correlation and diagnostic accuracy were evaluated among the 15 observers and 4 groups. The Cohen κ coefficient and Fleiss κ coefficient were used for the analysis. RESULTS: The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for senior sonologists were 93.3%, 100%, 89.6%, 84.4%, and 100%, respectively; for junior sonologists, 70.0%, 88.9%, 59.4%, 55.2%, and 90.5%; for general gynecologists, 75.2%, 88.1%, 78.1%, 69.8%, and 91.9%; and for advanced laparoscopists, 82.4%, 91.9%, 90.8%, 82.9%, and 95.8%. The overall agreement between senior sonologists was almost perfect (Fleiss κ = 0.876); for junior sonologists and general gynecologists, it was moderate (Fleiss κ = 0.589 and 0.528); and for advanced laparoscopists, it was substantial (Fleiss κ = 0.652). CONCLUSIONS: Interobserver agreement was superior among senior sonologists. Prediction of POD obliteration using offline US videos by senior sonologists is comparable to offline assessments of laparoscopic videos by advanced laparoscopists for prediction of POD obliteration.

Doppler Color Scoring System in Women With an Incomplete Miscarriage: Interobserver and Intraobserver Reproducibility Study.

OBJECTIVES: Doppler Color Scoring (DCS) has been used to predict successful expectant management of incomplete miscarriage. The aim of this study was to assess inter- and intraobserver reproducibility of the DCS system in women with incomplete miscarriage noted on transvaginal sonography. METHODS: This was a prospective reproducibility study involving offline analysis of 32 prerecorded video sets on transvaginal sonography in real time of women with incomplete miscarriage. Vascularization of retained products of conception was recorded using the DCS system adopted from the International Ovarian Tumor Analysis group. Five gynecologic sonologists of varying experience assigned a DCS classification to each video in the analysis. The same videos were reanalyzed, in a different order, at least 7 days later, to assess intraobserver agreement. Inter- and intraobserver correlations were performed to determine agreement. Interobserver agreement was also measured between each observer and the reference standard (G.C.). A Cohen's κ coefficient value less than 0 suggests poor agreement, 0.01 to 0.20 slight, 0.21 to 0.40 fair, 0.41 to 0.60 moderate, 0.61 to 0.80 substantial, and 0.81 and 0.99 almost perfect. RESULTS: Interobserver agreement for all observers for DCS allocation ranged from 0.480 to 0.751. Overall interobserver agreement for 5 observers was substantial (κ, 0.626). Overall interobserver agreements for the 2 inexperienced and 3 experienced observers compared to G.C. were 0.521 and 0.618, respectively. Experienced observers achieved overall almost perfect intraobserver agreement, compared to substantial agreement for inexperienced sonologists. CONCLUSIONS: DCS interobserver reproducibility between all observers and GC ranged from moderate to substantial. DCS intraobserver reproducibility was substantial to almost perfect. The DCS system appears to be a reproducible tool in evaluating women with incomplete miscarriage.

Is there a correlation between aberrant embryonic crown-rump length growth velocities and subsequent birth weights?

In this study, we tested the hypothesis that anomalous first trimester growth affects birth weight. Four hundred and fifteen women with viable singleton pregnancies at the primary transvaginal scan who had at least two crown rump length (CRL) and birth weight data were included. A linear mixed model was fitted to the Box-Cox transformed CRL values to evaluate the association between the GA and the embryonic growth. For multivariate analysis we included maternal age, height, weight, parity, number of miscarriages, vaginal bleeding, smoking, foetal gender, birth weight, small-for-gestation (SGA) and large-for gestation (LGA) categories at delivery. Smoking appeared to be significant for predicting the initial CRL from the beginning of the pregnancy (p value = 0.013). The SGA foetuses appeared to have slightly slower embryonic growth rates compared to non-SGA (p value = 0.045), after taking into account the effect of smoking on the initial CRL. None of the other variables including subsequent birth weight or LGA category have statistically significant effect on the first trimester embryonic growth curve when tested separately.

Prediction of subsequent miscarriage risk in women who present with a viable pregnancy at the first early pregnancy scan.

OBJECTIVES: To generate and evaluate a new prediction model for miscarriage in women who present with a viable intrauterine pregnancy (IUP) at the primary early pregnancy scan and to compare this new model to a previously published model. MATERIALS AND METHODS: Data were collected prospectively from women presenting to the early pregnancy unit with a viable IUP between November 2006 and January 2013. More than 30 historical, clinical and ultrasonographic variables were recorded on a standardised datasheet at the first visit. Women were followed until the final outcome was known at the end of the first trimester: viable IUP or miscarriage. A new multinomial logistic regression model was developed retrospectively on training cases and tested prospectively on test cases. The performance of the new prediction model was evaluated using receiver operating characteristic (ROC) curves and compared to a previously published model. After removing cases with missing values for the model of Oates, the area under the ROC curve (AUC) was also calculated for the new model and the Oates model. RESULTS: A total of 1115 consecutive first-trimester women presented to the early pregnancy unit. Eight hundred and sixty-two women with a viable IUP at the first scan whose outcome was known at the end of the first trimester were included in the final analysis. Five hundred and sixty-six women were included in the training set and 296 in the test set. 92.1% were viable and 7.9% had miscarried at the end of the first trimester. The most significant independent prognostic variables for the logistic regression model were as follows: maternal age, embryonic heart rate (EHR), logarithm [gestational sac (GS) volume/crown-rump length (CRL)], CRL and the presence or absence of clots per vagina (PV) at presentation. The performance of the new model compared with the Oates model gave an AUC of 0.870 vs 0.847 for the training set and 0.783 vs 0.744 for the test set. After removing cases with missing values for the model of Oates 2013, the performance of the new model compared to the Oates model gave an AUC of 0.887 vs 0.861 for the training set and 0.816 vs 0.734 for the test set (P-value <0.04). CONCLUSIONS: We have developed a new prediction model which indicates the likelihood of miscarriage. In women who present with a viable IUP at the primary scan, advancing maternal age in the presence of clots PV increases the probability of subsequent miscarriage. Whereas, in women with a higher EHR in the presence of an increased GS volume/CRL ratio, the likelihood of subsequent miscarriage is reduced. This new model outperforms the previously published model developed in our unit.

Prediction of successful expectant management of first trimester miscarriage: development and validation of a new mathematical model.

OBJECTIVE: To generate and evaluate a new logistic regression model for the prediction of successful expectant management of first trimester miscarriage. METHODS: Data were collected prospectively from women diagnosed with 1st trimester miscarriage. Clinical and ultrasonographic variables were recorded for multivariate analysis. Clinically stable women who were managed expectantly were followed up for two weeks until the outcome was established: success or failure. A multinomial logistic regression (MLR) model was developed on 186 training cases for the prediction of successful expectant management and tested prospectively on a further 126 cases. The performance of the model was evaluated using receiver operating characteristic (ROC) curve as well as in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Two thousand and forty eight consecutive first trimester women underwent TVS. Complete data from 312 (15.2%) women with miscarriage managed expectantly were included in the final analysis. The most important independent prognostic variables for the MLR model were as follows: type of miscarriage at primary scan, vaginal bleeding and maternal age. When developed retrospectively on a training data set, MLR model gave an area under the ROC curve (AUC) of 0.796. Prospective validation of MLR model on a new test data set resulted in an AUC of 0.803. CONCLUSION: We have developed and validated a new mathematical model to predict successful management of first trimester miscarriage.

Does symptomatology at presentation correlate with successful expectant management of first trimester miscarriage: a prospective observational study.

AIMS: To evaluate whether symptomatology at presentation correlates with successful expectant management of first-trimester miscarriage. METHODS: Data were collected prospectively on women managed expectantly for two weeks with first-trimester miscarriage. Women diagnosed with incomplete, missed and empty sac miscarriage were included. The overall rate of successful expectant management was evaluated in terms of symptomatology. The rates of successful expectant management for each miscarriage group were also evaluated in terms of the type of symptoms. Main outcome measure was success of expectant management at two weeks. RESULTS: Spontaneous completion of miscarriage was observed in 76.7% (161/210) women. The overall rates of successful expectant management were significantly different between the symptomatic (79.1%) and asymptomatic (42.9%) groups (P-value = 0.0003). In the incomplete miscarriage group, higher rates of success were associated with vaginal bleeding than without (89.4 vs 56.3%; P-value = 0.0027). The presence or absence of pain was not found to be significant. CONCLUSIONS: Symptomatology does appear to be a consistent predictor of outcome for expectant management of miscarriage. Overall, vaginal bleeding at presentation was associated with an increase in success of expectant management; but individually, only significant in the incomplete miscarriage group. The presence or absence of pain at presentation was not a predictor for the various types of miscarriage.

A prediction model for viability at the end of the first trimester after a single early pregnancy evaluation.

OBJECTIVE: The aim was to develop a new model to predict the outcome at the end of the 1st trimester after a single visit to the early pregnancy unit (EPU). METHODS: Prospective observational study in the EPU at Nepean Hospital, between November 2006 and February 2009. Data were collected from all women in the 1st trimester of their pregnancy who had a live intrauterine pregnancy (IUP) at the 1st transvaginal ultrasound scan (TVS). 29 historical, clinical and ultrasound end points were recorded. Women were followed until the final diagnosis was established at the end of the 1st trimester: viability or nonviability. A multinomial logistic regression model was developed. The performance of this model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: Data from 416 pregnancies were included: 92.1% were live beyond the 1st trimester, and 7.9% had miscarried. The most useful prognostic variables for developing the logistic regression model were gestational age by dates, vaginal (PV) bleeding, PV clots, gestational age by TVS, consistency with menstrual dates, mean gestational sac (GS) size, mean yolk sac (YS) size and number of previous caesarean sections. Used retrospectively on 416 women based on 25 imputations, the model gave an AUC of 0.88. Based on cross-validation, the independent predictive power obtained an AUC of 0.78. CONCLUSIONS: We have developed a new model to predict the outcome of the 1st trimester in women with live IUP at the 1st scan.

The use of power Doppler colour scoring to predict successful expectant management in women with an incomplete miscarriage.

OBJECTIVE: To evaluate whether the use of power Doppler to confirm the presence or absence of blood flow within retained products of conception (RPC) in women with an incomplete miscarriage can predict subsequent successful expectant management. METHODS: Prospective observational study in the Acute Gynaecology and Early Pregnancy Unit (AGEPU) at Nepean Hospital from November 2006 to February 2009. Incomplete miscarriage was defined by the presence of a measurable focus of hyperechoeic material, in three planes, within the endometrial cavity using two-dimensional greyscale transvaginal ultrasound (TVS). Subjective qualitative power Doppler colour scoring (PDCS) of the RPC was performed. The vascularization of the RPC was scored using the colour scoring system of the International Ovarian Tumour Analysis (IOTA) group. PDCS 1 meant absence of vascularity, PCDS 2 represented minimal vascularity, PDCS 3 rather strong vascularity and PDCS 4 very strong vascularity. The correlation between the PDCS and successful expectant management of miscarriage was analysed. The volume of RPC was calculated using the ellipsoid formula and then compared with both the PDCS and the outcome of expectant management. Successful expectant management was defined as the resolution of symptoms and the absence of RPC on follow-up TVS. RESULTS: A total of 1395 consecutive pregnant women underwent TVS. Of them, 198 women were diagnosed with an incomplete miscarriage; 172 were managed expectantly. Complete data were available on 158 cases. In total 84.8% (134/158) were managed successfully whilst 15.2% (24/158) failed expectant management. Of the total, 89% (121/136) of women with a PDCS 1 had successful expectant management compared with 57.1 (8/14) with PDCS 2 and 62.5% (5/8) with PDCS 3. Comparing absence of flow (PDCS 1) to presence of flow (PDCS 2 or more), the rate of success was significantly higher in the first group (89 versus 60.9%, Fisher's exact test P= 0.00136). In the prediction of success, the absence of flow showed a sensitivity, specificity, positive predictive value, negative predictive value and positive likelihood ratio of 90.3, 37.5, 89, 40.9% and 1.445 (95% confidence interval: 1.055-1.979), respectively. There was no correlation between the volume of RPC and the PDCS; and there was no relationship between the volume of RPC and the success of expectant management. CONCLUSIONS: PDCS can predict the likelihood of successful expectant management of incomplete miscarriage. The absence of flow on power Doppler is associated with a significant improvement in the rate of successful expectant management. This new approach may be helpful in quantifying the chances of successful expectant management in those women with an incomplete miscarriage at the primary scan.

Ectopic pregnancy: Ultrasound diagnosis in modern management.

Ectopic pregnancy (EP) continues to be the number one cause of maternal deaths in the first trimester of pregnancy. Over the past 30 years, several key developments including accurate and rapid serum human chorionic gonadotrophin assays, the introduction of high-resolution transvaginal probes and more recently tertiary hospital Early Pregnancy Units have changed the management of EPs. Early transvaginal ultrasound diagnosis of EP not only potentially decreases mortality and surgical intervention rates, but also promotes modern management options including expectant or medical management. The aim of this review is to demonstrate that transvaginal ultrasound is the new 'gold standard' diagnostic tool of choice for all forms of EP.

Chlamydia trachomatis in fallopian tubes of women undergoing laparoscopy for ectopic pregnancy.

OBJECTIVES: To study whether Chlamydia trachomatis is absent or persists in a latent state in the fallopian tube at the time of laparoscopic salpingectomy for tubal ectopic pregnancy (EP). METHODS: We examined tissue of the fallopian tubes for the presence of C. trachomatis from women who underwent laparoscopic salpingectomy for EP. Presence or absence of C. trachomatis was assessed using both Probe Tec ET (define Tec and ET please) and real-time polymerase chain reaction (PCR) (Ausdiagnositic STD 6 assays) DNA amplification. RESULTS: Fresh tubal tissue from 17 women with histological confirmation of EP was examined in a hospital setting for the presence of C. trachomatis. The presence of C. trachomatis DNA was confirmed by PCR using a commercial test (BD ProbeTec ET System), and a real-time enhanced PCR able to detect few copies of the organism. Chlamydia DNA was detected in 0/16 tubal specimens, and in one case, the PCR analysis was not possible for presence of inhibitors. CONCLUSIONS: We did not find any evidence of latent infection of C. trachomatis in the fallopian tube at the time of laparoscopic salpingectomy for EP in our study. Although the numbers are small, our results suggest that EP can be considered a late complication of the tubal damage resulted from a previous acute Chlamydia infection and that EP may not be related to a latent persistence of Chlamydia in the fallopian tube.

Estimation of uterine volume: A comparison between Viewpoint and 3D ultrasound estimation in women undergoing laparoscopic hysterectomy.

Objectives: To assess the three-dimensional (3D) tool, Virtual Organ Computed-aided AnaLysis™ (VOCAL) in the calculation of pre-operative uterine volume and to correlate the measurements with those obtained with Viewpoint, using uterine dry weight (UDW) as the gold standard. Methods: Prospective observational study of women consented for a laparoscopic hysterectomy (LH) at Nepean Hospital between October 2008 and November 2011. All women underwent detailed transvaginal scan (TVS) at the pre-operative assessment. Two-dimensional (D) images of the uterus were obtained both in the mid-sagittal and transverse planes. 3D volumetric acquisitions were also obtained for each uterus in the mid-sagittal plane. 2D measurements of the uterus in millimetres (Anterio-Posterior, longitudinal and transverse) were recorded in Viewpoint software package (GE Healthcare ViewPoint, Germany); which then generated an estimated uterine volume (ml) using the ellipsoid formula. The 3D uterine volumetric datasets were reviewed using SonoView Pro and uterine volumes were estimated with off-line processing using VOCAL™. The gold standard for comparison was UDW in grams (g), measured by the histopathologist at the time of analysis of the LH specimens. The relationship between the estimated uterine volumes and actual UDW was evaluated using correlation analysis. P-values were calculated to ascertain the significance of these findings; P values &< 0.05 represented statistical significance. Results: 76 women underwent LH during the study period. Complete data were available in 96% (74/76) of cases. The mean age of the women was 43.7 years and 92% were multiparous. The mean Viewpoint uterine volume was 283 ml, the mean VOCAL™ uterine volume was 249 ml and the mean UDW was 295 g. There was a significant correlation between UDW and estimated uterine volumes both for Viewpoint (R = 0.83, P < 0.001) and VOCAL™ (R = 0.97, P < 0.001), respectively. Viewpoint systematically overestimated weight by 43.1 g, whereas VOCAL™ underestimated by an average of 42.4 g, and this difference was statistically significant (P < 0.001). In terms of absolute values, the mean prediction error for VOCAL™ was -18.0 g and for Viewpoint it was 27.6 g (P &< 0.0001). Conclusion: VOCAL™ was found to be significantly more accurate than Viewpoint in the estimation of uterine volumes, and it was better correlated with UDW.

The use of interventional ultrasound in early pregnancy complications.

Background: The use of ultrasound to establish pregnancy location, viability and gestational age in the first trimester is well established. In addition to the conventional uses of ultrasound in early pregnancy, interventional ultrasound may also be used to guide clinicians during surgical procedures for the management of early pregnancy complications (i.e. treatment of ectopic pregnancy, caesarean section scar pregnancy, molar pregnancy, retained products of conception, and removal of intra-uterine devices in early pregnancy). Aims: This review discusses the role of interventional ultrasound as it pertains to the management of first trimester complications, particularly with regard to the use of ultrasound in conjunction with surgical modalities. Materials and Methods: This review was based on recently published research, as cited in the PubMed database, regarding the use of either transvaginal or transabdominal ultrasound to assist with the management of early pregnancy complications. Conclusions: In addition to the diagnostic capabilities of ultrasound in early pregnancy, interventional ultrasound plays an important role in the management of various first trimester pregnancy complications. With the advent of more conservative approaches to early pregnancy complications, interventional ultrasound is a viable option which is not only safe in experienced hands but also enables fertility preservation.

Rationalising the change in defining non-viability in the first trimester.

Introduction: With the publication of four papers in late 2011, international cut-offs for definitions of non-viability in the first trimester of pregnancy were challenged. These definitions were inconsistent across different international guidelines. For example, a gestational sac with absent yolk sac or embryo and a mean diameter of ≥ 16 mm would be classified as a miscarriage in the USA, whereas the same sac would have to measure ≥ 20 mm in the UK or Australia to meet this definition. Likewise, an embryo with no detectable heartbeat and a CRL of ≥ 5 mm would also meet criteria for missed miscarriage in the USA, compared to a CRL ≥ 6 mm in the UK or Australia. Methods: Later in 2011 and then in 2012, guidelines across the three countries were updated and are now consistent, defining an empty gestational sac with a mean diameter of > 25 mm as a non-viable pregnancy and/or an embryo with CRL > 7 mm and no detectable heartbeat. In this paper we explore the rationale that led to these changes in order to potentially avoid wrongly diagnosing miscarriage at the decision boundary measurements and in turn avoiding inadvertent termination of potentially viable pregnancies. Conclusion: Although reducing women's anxiety and making a definitive diagnosis as early as possible is desirable, the need for absolute certainty is paramount before diagnosis of the death of an early pregnancy is made.

Serum biomarkers for ectopic pregnancy diagnosis.

INTRODUCTION: Ectopic pregnancy (EP) remains the leading cause of maternal mortality in the first trimester of pregnancy. In an attempt to expedite the accurate diagnosis of women with EP, research has focused on serum biomarkers that can distinguish EP from other types of pregnancies in women with a pregnancy of unknown location (PUL). AREAS COVERED: This review was based on recently published research, as cited on the PubMed database, regarding the major serum biomarkers, which have been evaluated to distinguish EP from failed PULs or normal intrauterine pregnancies (IUPs). EXPERT OPINION: At present, there is no single biochemical marker or combination of biomarkers that consistently predicts EP with both high sensitivity and specificity. Current diagnostic strategies in women with a PUL result in costly multiple visits. This approach both burdens the health-care system fiscally and impacts on the psychological morbidity of the individual. What is needed is a cost-effective diagnostic serum biomarker/s test to accurately predict EP in the PUL population. This strategy could significantly reduce follow-up visits, without compromising maternal mortality.

Methotrexate vs placebo in early tubal ectopic pregnancy: a multi- centre double-blind randomised trial.

BACKGROUND: In the 21st century, tubal ectopic pregnancies (EPs) are diagnosed earlier in their natural history due to transvaginal ultrasound technology. More women are haemodynamically stable and therefore can be offered non-invasive outpatient management with systemic Methotrexate (MTX). However there is no evidence that MTX is necessary in all these early EPs, as many may resolve spontaneously in the absence of any treatment. To date there are no published randomized trials comparing systemic MTX with a placebo. The aim of this study is to verify if MTX is more effective than the placebo in women with tubal EP and rising/plateauing serum human chorionic gonadotrophin (hCG) levels. METHODS/DESIGN: This is a multi-centre double-blind randomized controlled trial conducted in Australia. Haemodynamically stable women with a confirmed ultrasound diagnosis of tubal EP and a rising/plateauing serum hCG & < 1500 IU/L are eligible for the trial. Women with a declining serum hCG, hCG > 1500 IU/L at 48 hrs, viable tubal EP, severe abdominal pain, evidence of haemoperitoneum on ultrasound, diagnostic uncertainty, non-tubal ectopic pregnancy, or women with contraindications to MTX will be excluded. Systemic MTX in a single dose intramuscular regimen (50mg/m2) is compared to an identical placebo in an outpatient setting. All women will attend for a serum hCG measurement on day 4. Provided patients are haemodynamically stable, they will attend for another blood test on day 7. If a decline in serum hCG > 15% between days 4 - 7 is observed, weekly blood tests will be scheduled until undetectable hCG levels. If serum hCG levels increase or decrease < 15% between days 4 - 7, a second dose of MTX will be given and weekly blood tests will be scheduled until undetectable serum hCG. If any increase in serum hCG > 15% between days 4 - 7 or at any subsequent follow-up, women will be treated with MTX. Primary outcome measure is treatment success, defined as uneventful decline of serum hCG to an undetectable level ( < 5 IU/L) by the initial intervention. Secondary outcome measures are re-interventions (additional systemic MTX injections and/or surgery for haemodynamic instability/trophoblast persistence), treatment complications and length of follow-up. DISCUSSION: This trial will clarify the actual effectiveness of MTX in haemodynamically stable women with an early tubal EPs and rising or plateauing hCG.