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.

Prognostic accuracy of a novel methotrexate protocol for the resolution of tubal ectopic pregnancies.

OBJECTIVE: To evaluate if a decreasing human chorionic gonadotropin (hCG) between day (D) 1 and D7 is an equal or better predictor of tubal ectopic pregnancy (EP) resolution following methotrexate (MTX) treatment than the current standard of care. STUDY DESIGN: This was a retrospective cohort prognostic accuracy study of women with a transvaginal ultrasound (TVS)-confirmed tubal EP (November 2006-December 2015). After single-dose MTX treatment, D4/7 hCG ratios were compared with that of D1/D7 in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to predict EP resolution. RESULTS: Tubal EP was diagnosed in 301/7350 (4.1%) women who underwent TVS for early pregnancy-related complaints. The patients were managed accordingly: expectant, 84/301 (27.9%); MTX, 65/301 (21.6%); surgery, 152/301 (50.5%). A D1/D7 hCG ratio ≤0.85 predicted successful resolution of tubal EPs (P < 0.001) treated with MTX with sensitivity 0.84 [95% confidence interval (CI), 0.69-0.94]), specificity 0.71 [95%CI, 0.48-0.89], PPV 0.84 [95%CI, 0.69-0.94], NPV 0.84 [95%CI, 0.69-0.94], which is comparable to the prognostic performance of the D4/7 protocol. CONCLUSION: In patients with tubal EP carefully selected for and treated with MTX, it may be reasonable to eliminate the D4 hCG in the follow-up algorithm.

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.

Rationalizing the management of pregnancies of unknown location: Diagnostic accuracy of human chorionic gonadotropin ratio-based decision tree compared with the risk prediction model M4.

INTRODUCTION: The objective was to compare the diagnostic accuracy of the decision tree analysis prediction model P1, which incorporates the human chorionic gonadotropin (hCG) ratio (hCG 48 hours/hCG 0 hour), and risk prediction model M4 in the management of women with pregnancy of unknown location (PUL). MATERIAL AND METHODS: A retrospective diagnostic accuracy study was performed on PUL data collected between August 2011 and September 2018. Women with a PUL were prospectively managed according to the P1 prediction model, which utilizes the hCG ratio and, if necessary, a day (D) 7 hCG. We compared the performance of P1 with the M4 model, a logistic regression mathematical model using initial hCG and hCG ratio, to classify PULs as low risk (failed PUL [failed] or intrauterine pregnancy) or high risk (ectopic pregnancy or persistent PUL). The reference standard was defined as the final PUL outcome. RESULTS: Transvaginal ultrasound was done in 3847 consecutive women for early pregnancy complications, 437 (11.3%) of whom were classified as PUL. Final analysis comprised 413 cases with complete data. Final PUL clinical outcomes were: 247 (59.8%) failed PUL, 94 (22.7%) intrauterine pregnancy, 49 (11.8%) ectopic pregnancy and 23 (5.5%) persistent PUL. The sensitivity of P1 and M4 in predicting high-risk PUL were 81.9% (95% confidence interval [CI] 71.1-90.0) and 80.6% (95% CI 69.5-88.9), respectively. The specificities were 74.5% (95% CI 69.5-79.1) and 75.6% (95% CI 70.7-80.1), respectively. CONCLUSIONS: P1 and M4 performed similarly with respect to diagnostic accuracy in predicting PUL outcome. P1 needs to be externally validated.

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.

Relationship Between Ultrasonographic and Biochemical Markers of Tubal Ectopic Pregnancy and Success of Subsequent Management.

OBJECTIVES: To determine whether there is an association between morphologic types of tubal ectopic pregnancy (EP), 0-hour human chorionic gonadotropin (hCG) levels, and subsequent management success. METHODS: We conducted a prospective study (November 2006-December 2015). Women had a diagnosis of EP by transvaginal ultrasonography if they had an inhomogeneous mass adjacent to the ovary and moving separately from it ("blob" sign), a mass with a hyperechoic ring around the gestational sac ("bagel" sign), or a gestational sac with an embryonic pole with or without a yolk sac with or without cardiac activity. The morphologic type, EP size, and 0-hour hCG level were analyzed. A multivariate analysis determined any correlation between these variables and nonsurgical management success. RESULTS: A total of 7350 consecutive women underwent transvaginal ultrasonography, of whom 301 (4.2%) had a diagnosis of tubal EP; 181 (60.1%) had the blob sign; 90 (29.9%) had the bagel sign; and 23 (7.6%) were noted to have an embryo (14 viable and 9 nonviable). Eighty-three of 301(27.5%) women had expectant management; 67 of 301(22.2%) were given methotrexate; and 151 of 301 (50%) had surgery. Success rates for the groups were 77%, 75%, and 100%, respectively. No difference between the morphologic type and success rate of treatment was noted. Although there was a significant correlation between the EP mass size and 0-hour hCG level, the mass size itself was not correlated with the success rate of either medical or expectant management. Overall higher 0-hour hCG levels were associated with management failure. In the expectant group, median hCG level for failure was 589 IU/L versus 366 IU/L for success, whereas in the medical group, the median for failure was 1244 IU/L versus 7629 IU/L for success. CONCLUSIONS: There is no significant correlation between the morphologic type and size of EP with a nonsurgical management outcome. A likely successful outcome is related to a lower level of serum hCG at presentation.

Do we perform too many procedures for cervical dysplasia in young women?

OBJECTIVE: This study aimed to determine if there are differences in the histological findings of excisional biopsies between younger women (aged ≤25 years) and older women who undergo large loop excision of the transformation zone or cone biopsy for a biopsy-proven high-grade squamous intraepithelial lesion (HSIL). MATERIALS AND METHODS: A retrospective cohort analysis of women referred to a tertiary hospital colposcopy clinic with a colposcopically directed biopsy of HSIL (cervical intraepithelial neoplasia 2 [CIN 2] or CIN 3) during the period of 2008 to 2011 was performed.The histological excisional biopsy specimens for younger women (aged ≤25 years) were compared with those of older women (aged >25 years.) Bivariate analysis comparing demographic characteristics and outcomes across the 2 study groups was initially undertaken to identify potential confounders for inclusion in the multivariate analysis. RESULTS: Of 348 women who had a satisfactory colposcopic assessment and reported no previous treatment for cervical intraepithelial neoplasia, 87 were 25 years or younger, and 261 women were older than 25 years. After excisional biopsy of the cervix, the histological specimen for younger women was more likely to be reported as CIN 1 or no dysplasia (16.3% vs 8.2%). When adjusted for confounders (parity, smoking, previous sexual infection, and referring Pap smear), age less than 25 years remained an independent predictor of having a histological excisional biopsy specimen reported as CIN 1 or no dysplasia (adjusted odds ratio = 2.35; 95% confidence interval = 1.0-5.49). CONCLUSIONS: Younger women with biopsy-proven HSIL (CIN 2/3), have a higher likelihood that the histological specimen after an excisional biopsy of the cervix will be reported as CIN 1 or no dysplasia.