Temporal and external validation of the algorithm predicting first trimester outcome of a viable pregnancy.

BACKGROUND: Symptoms like vaginal bleeding or abdominal pain in early pregnancy can create anxiety about potential miscarriage. Previous studies have demonstrated ultrasonographic variables at the first trimester transvaginal scan (TVS) which can assist in predicting outcomes by 12 weeks gestation. AIM: To validate the miscarriage risk prediction model (MRP) in women who present with a viable intrauterine pregnancy (IUP) at the primary ultrasound. MATERIALS AND METHODS: A multi-centre diagnostic study of 1490 patients was performed between 2011 and 2019 for retrospective external and 2017-2019 for prospective temporal validation. The reference standard was a viable pregnancy at 12 + 6 weeks. The MRP model is a multinomial logistic regression model based on maternal age, embryonic heart rate, logarithm (gestational sac volume/crown-rump length (CRL)) ratio, CRL and presence or absence of clots. RESULTS: Temporal validation data from 290 viable IUPs were collected: 225 were viable at the end of the first trimester, 31 had miscarried and 34 were lost to follow-up. External validation data from 1203 viable IUPs were collected at two other ultrasound units: 1062 were viable, 69 had miscarried and 72 were lost to follow-up. Temporal validation with a cut-off of 0.1 demonstrated: area under the curve (AUC) of 0.8 (0.7-0.9), sensitivity 66.7%, specificity 83.9%, positive predictive value (PPV) 35.7%, negative predictive value (NPV) 94.9%, positive likelihood ration (LR+) 4.1 and negative LR (LR-) 0.4. External validation demonstrated: AUC 0.7 (0.7-0.8), sensitivity 44.9%, specificity 90.4%, PPV 23.3%, NPV 96.2%, LR+ 4.6 and LR- 0.6 (0.4-0.7). CONCLUSION: The MRP model is not able to be used in real time for counselling, and management should be individualised.

The effect of cigarette smoking on first-trimester crown-rump length.

Objectives: Does cigarette smoking impact the embryonic growth rate in the first trimester? Methods: This is a retrospective multicentre observational study of 2912 pregnancies. Women who presented to the early pregnancy and perinatal ultrasound units between 2010 and 2019 were included in the study. The data collected included the following: smoking status, the crown-rump length (CRL) of the pregnancy at the first ultrasound that showed an embryonic heart rate, the gestation in days and the CRL at another ultrasound up to the nuchal translucency scan and the gestation in days. Additional demographic data included the following: age, weight, height, parity and mode of delivery.Of the 2912, complete smoking and demographic data were available for 657 pregnancies. One hundred and thirty-seven (26.3%) were smokers, and 520 (73.7%) were not. The rate of change of smokers vs non-smokers between two CRLs and two different days of gestation was calculated. The Wilcoxon rank sum test with continuity correction was used for statistical analysis. Results: This gives a value of W = 31,940 and a P-value = 0.06. There is a slight shift in location for the smokers; however, it is not statistically significant. The insignificance may be due to the general large variance in growth rate. Conclusion: The impact of cigarette smoking on embryonic growth rate detected by CRL in the first trimester is statistically insignificant.

External validation of risk prediction model M4 in an Australian population: Rationalising the management of pregnancies of unknown location.

BACKGROUND: The prediction model M4 can successfully classify pregnancy of unknown location (PUL) into a low- or high-risk group in developing ectopic pregnancy. M4 was validated in UK centres but in very few other countries outside UK. AIM: To validate the M4 model's ability to correctly classify PULs in a cohort of Australian women. MATERIALS AND METHODS: A retrospective analysis of women classified with PUL, attending a Sydney-based teaching hospital between 2006 and 2018. The reference standard was the final characterisation of PUL: failed PUL (FPUL) or intrauterine pregnancy (IUP; low risk) vs ectopic pregnancy (EP) or persistent PUL (PPUL; high risk). Each patient was entered into the M4 model calculator and an estimated risk of FPUL/IUP or EP/PPUL was recorded. Diagnostic accuracy of the M4 model was evaluated. RESULTS: Of 9077 consecutive women who underwent transvaginal sonography, 713 (7.9%) classified with a PUL. Six hundred and seventy-seven (95.0%) had complete study data and were included. Final outcomes were: 422 (62.3%) FPULs, 150 (22.2%) IUPs, 105 (15.5%) EPs and PPULs. The M4 model classified 455 (67.2%) as low-risk PULs of which 434 (95.4%) were FPULs/IUPs and 21 (4.6%) were EPs or PPULs. EPs/PPULs were correctly classified with sensitivity of 80.0% (95% CI 71.1-86.5%), specificity of 75.9% (95% CI 72.2-79.3%), positive predictive value of 37.8% (95% CI 33.8-42.1%) and negative predictive value of 95.3% (95% CI 93.1-96.9%). CONCLUSIONS: We have externally validated the prediction model M4. It classified 67.2% of PULs as low risk, of which 95.4% were later characterised as FPULs or IUPs while still classifying 80.0% of EPs as high risk.

One-Size-Fits-All Approach Does Not Work for Gynecology Trainees Learning Endometriosis Ultrasound Skills.

OBJECTIVES: To evaluate whether gynecologic surgical trainees (fellows) can become competent in the real-time classification of the pouch of Douglas (POD) obliteration state and direct visualization of bowel deep endometriosis (DE) during a program with a prespecified number of transvaginal ultrasound (TVUS) examinations. METHODS: We performed a prospective study between December 2017 and December 2018. Three fellows (F1-F3) performed 50 scans each, which were all supervised by an expert sonologist, who performed the reference standard TVUS examination. The fellows performed a focused TVUS examination to assess the bowel and POD state, having been blinded to the patient's clinical history and reference standard findings. Immediate feedback and hands-on teaching were provided after each of the fellow's official classifications. To evaluate the number of scans needed to gain competency, the cumulative summation test for the learning curve was used. RESULTS: A total of 150 examinations were performed on 145 patients. Twenty-six (17.9%) patients had a diagnosis of bowel DE, and 34 (23.4%) were classified as having a negative sliding sign by the reference standard. The overall accuracy of the presence/absence of bowel DE was 90% (range, 82%-94%). The overall accuracy of POD state classification was 93% (range, 90%-96%). The cumulative summation test for the learning curve for bowel DE showed that F1 did not reach competency by 50 scans, whereas F2 and F3 required 21 and 25 scans, respectively. For POD obliteration, F2 did not reach competency, whereas F1 and F3 required 40 and 22 scans. CONCLUSIONS: Not all trainees can reach competency for TVUS evaluations of POD obliteration and bowel DE in a predefined number of scans.

Ureter Visualization With Transvaginal Ultrasound: A Learning Curve Study.

OBJECTIVES: To evaluate the learning curve of gynecologic surgical fellows (ie, in training) to properly identify the ureters in real time while simultaneously performing and interpreting transvaginal ultrasound (TVUS) examinations. METHODS: We performed a prospective study, which took place at 2 centers in Sydney, Australia, from December 2017 to December 2018. Three fellows (F1-F3), of varying prestudy ultrasound (US) experience, were recruited to participate. One hundred fifty predetermined examinations were planned. A TVUS examination was performed by the study reference standard (an expert in gynecologic US). Subsequently, the fellows performed a focused component to identify bilateral ureters, having been blinded to the patient's clinical history and reference standard findings. Immediate feedback and hands-on teaching were provided after each of the fellow's evaluations were complete. To evaluate the number of scans needed to gain competency, the cumulative summation test for the learning curve was used. RESULTS: A total of 150 examinations were performed on 145 patients. One patient had a single ureter, and 1 patient had US evidence of hydroureter. The cumulative summation test for the learning curve for bilateral ureter identification showed that F1 did not reach competency by 50 TVUS examinations, whereas F2 and F3 required 41 and 31 TVUS examinations to reach competency, respectively. CONCLUSIONS: Contrary to other studies on the topic, this study suggests that although it is feasible for surgical fellows to learn TVUS identification of bilateral ureters, not all fellows can reach competency during a program based on a predefined number of scans. We advocate for an individualized, competency-based medical education model in learning US for identifying the ureters.

Concurrent Escherichia coli tubo-ovarian abscess and Campylobacter jejuni gastroenteritis: A case report.

Haematogenous or direct spread of bacterial infection causing pelvic inflammatory disease of the upper female reproductive tract is uncommon. We report a diagnostically challenging case of a 41-year-old woman with a background of Stage 4 endometriosis presenting with fever, diarrhoea and abdominal pain with recent history of pyelonephritis. Initially managed for undifferentiated abdominal pain with unclear focus of infection, a broad range of investigations were undertaken. Laboratory samples confirmed the presence of Campylobacter jejuni and appropriate treatment for Campylobacteriosis was commenced. Despite treatment, her condition deteriorated and repeat radiological imaging revealed bilateral tubo-ovarian abscess requiring surgical drainage for control of severe sepsis. Sterile surgical samples of the abscess revealed Escherichia coli. This case adds to the growing body of evidence of the association between pelvic inflammatory disease, severe endometriosis and development of tubo-ovarian abscess. Sepsis associated with tubo-ovarian abscess has a mortality rate of up to 10%. Hence, we present this case to highlight severe endometriosis as a risk factor for disease and the need for prompt reassessment of the deteriorating woman with sepsis and pelvic pain to direct efforts to minimise morbidity and mortality.

Pre-operative classification of molar pregnancy: How good is ultrasound?

BACKGROUND: Histopathology is the reference standard for diagnosing hydatidiform molar pregnancy (HMP). AIM: To assess the performance of pre-operative transvaginal ultrasound (TVS) to predict HMP. MATERIALS AND METHODS: A retrospective diagnostic accuracy study was performed on women who had both TVS and histopathological examination of uterine curettings between January 2011-February 2017. TVS diagnosis of partial MP (PMP) included assessment of fetal parts and/or empty gestational sac with small cystic spaces adjacent to gestational sac. TVS diagnosis of complete MP (CMP) included assessment of complex, echogenic intra-uterine mass(es) containing multiple small cystic areas. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive and negative likelihood ratios (PLR/NLR) for TVS were reported. Reference standard was histology. RESULTS: There were 4917 consecutive women who underwent TVS; 1636 underwent surgical curettage for miscarriage. Forty out of 4917 (0.6%) had HMP histologically; 25/40 (62.5%) had suspected HMP and 15/40 (37.5%) did not; 24/40 (60.0%) had CMP of which 19/24 (79.1%) were suspected on TVS and 5/24 (20.8%) were not; 16/40 (40.0%) had PMP of which 6/16 (37.5%) were suspected on TVS and 10/16 (62.6%) were not. The sensitivity, specificity, PPV, NPV, PLR and NLR of pre-operative TVS to predict HMP were: 60.0, 99.1, 63.2, 99.0% 68.4, 0.4; for CMP: 79.2, 99.8, 86.3, 99.6%, 421.7, 0.2; for PMP: 37.5, 99.3, 35.3, 99.4%, 54.3, 0.6. CONCLUSION: Histology remains the gold standard for diagnosing HMP. TVS is an acceptable diagnostic tool for HMP. When there are no ultrasound features of HMP, almost all these women will not have an underlying HMP.

A Novel Ultrasound Technique Called Saline Infusion SonoPODography to Visualize and Understand the Pouch of Douglas and Posterior Compartment Contents: A Feasibility Study.

Women with infertility are often investigated with saline-infusion sonohysterography and hysterosalpingo-contrast-sonography. The high prevalence of endometriosis in this population also warrants an evaluation with transvaginal ultrasound for deep endometriosis. To minimize investigations, we prospectively evaluated the feasibility of a novel combined ultrasound technique called saline-infusion sonoPODography. In most patients, the fluid infused to assess the cavity and tubal patency spilled through patent tubes and filled the pouch of Douglas, yielding a "standoff" view of posterior compartment structures, including uterosacral ligaments, rectovaginal septum, and the pouch of Douglas. We believe this improved our ability to evaluate this space.

A severed IP ligament as a cause for trans-vaginal uterine bleeding post termination of pregnancy: a case report.

Uterine perforation is an uncommon yet serious complication of surgical management of first and second trimester termination of pregnancies. The rate of uterine perforation is under reported, as patients are usually asymptomatic. Although uncommon, uterine perforation can cause life-threatening complications for some patients. This case report discusses a second trimester surgical termination resulting in uterine perforation and haemorrhage secondary to an avulsion of the infundibulopelvic ligament and prolapse of the left fallopian tube and ovary into the uterine cavity. A literature search was undertaken to compare this case report to those previously published. To the best of our knowledge, this is the first case report in Australia that discusses a unique case of a severed infundibulo-pelvic ligament as a cause for trans-vaginal uterine bleeding post second trimester termination of pregnancy.

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.

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.

Is there a correlation between birth weights and first-trimester crown-rump length growth velocity?

OBJECTIVE: To test the hypothesis that small- or large-for-gestational-age (SGA or LGA) newborns have anomalous crown-rump length (CRL) growth rates in the first trimester. METHODS: Prospective observational study. Women in the first trimester presenting to the Early Pregnancy Unit, between November 2006 and December 2010, underwent transvaginal scan. Women with viable singleton pregnancies in the first trimester who had at least two CRL measurements > 5 mm, recorded at least 2 weeks apart, and also had birth weight data available were included in the final analysis. Birth weight percentiles were calculated and adjusted for gestational age and gender. SGA was equivalent to < 10th centile and LGA was equivalent to > 90th centile. Correlation analysis was performed between birthweight percentiles and first-trimester CRL growth-rate coefficients. In addition, we estimated early fetal growth rates (EFGR) by calculating the Δ CRL/Δ time (mm/day) to see if these differed according to the birth-weight percentiles. RESULTS: A total of 107 women had complete data. The mean maternal characteristics were age 27.5 ± 6 years, weight 87 ± 29 kg and height 163 ± 8 cm. The mean birth weight and gestational age at delivery were 3405 g (SD = 597) and 269 days (SD = 13), respectively. The proportions of SGA and LGA were 7.5% and 18.7%, respectively. There were no significant correlations between birth-weight percentiles and any of the CRL growth rates. There were also no significant differences in the mean CRL velocities when comparing the SGA and LGA newborns birth weights. EFGR for SGA and LGA newborns were 1.34 mm/day (SD = 0.17) and 1.32 mm/day (SD = 0.24), respectively (p > 0.05). CONCLUSIONS: Newborns who are found to be SGA or LGA at delivery do not appear to have anomalous CRL growth patterns in the first trimester. The EFGR also did not correlate with birth-weight percentiles.