The risk of miscarriage following surgical treatment of heterotopic extrauterine pregnancies.

STUDY QUESTION: What is the risk of loss of a live normally sited (eutopic) pregnancy following surgical treatment of the concomitant extrauterine ectopic pregnancy? SUMMARY ANSWER: In women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine ectopic pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. WHAT IS KNOWN ALREADY: Previous studies have indicated that surgical treatment of the concomitant ectopic pregnancy in women with live eutopic pregnancies could be associated with an increased risk of miscarriage. The findings of our study did not confirm that. STUDY DESIGN SIZE DURATION: A retrospective observational case-control study of 52 women diagnosed with live eutopic and concomitant extrauterine pregnancies matched to 156 women with live normally sited singleton pregnancies. The study was carried out in three London early pregnancy units (EPUs) covering a 20-year period between April 2000 and November 2019. PARTICIPANTS/MATERIALS SETTING METHODS: All women attended EPUs because of suspected early pregnancy complications. The diagnosis of heterotopic pregnancy was made on ultrasound scan and women were subsequently offered surgical or expectant management.There were three controls per each case who were randomly selected from our clinical database and were matched for maternal age, mode of conception and gestational age at presentation. MAIN RESULTS AND THE ROLE OF CHANCE: In the study group 49/52 (94%) women had surgery and 3/52 (6%) were managed expectantly. There were 9/52 (17%, 95% CI 8.2-30.3) miscarriages <12 weeks' gestation and 9/49 (18%, 95% CI 8.7-32) miscarriages in those treated surgically. In the control group, there were 28/156 (18%, 95% CI 12.2-24.8) miscarriages <12 weeks' gestation, which was not significantly different from heterotopic pregnancies who were treated surgically [odds ratio (OR) 1.03 95% CI 0.44-2.36]. There was a further second trimester miscarriage in the study group and one in the control group. The live birth rate in the study group was 41/51 (80%, 95% CI 66.9-90.2) and 38/48 (79%, 95% CI 65-89.5) for those who were treated surgically. These results were similar to 127/156 (81%, 95% CI 74.4-87.2) live births in the control group (OR 0.87, 95% CI 0.39-1.94). LIMITATIONS REASONS FOR CAUTION: This study is retrospective, and the number of patients is relatively small, which reflects the rarity of heterotopic pregnancies. Heterotopic pregnancies without a known outcome were excluded from analysis. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates that in women diagnosed with heterotopic pregnancies, minimally invasive surgery to treat the extrauterine pregnancy does not increase the risk of miscarriage of the concomitant live eutopic pregnancy. This finding will be helpful to women and their clinicians when discussing the options for treating heterotopic pregnancies. STUDY FUNDING/COMPETING INTERESTS: This work did not receive any funding. None of the authors has any conflict of interest to declare. TRIAL REGISTRATION NUMBER: Research Registry: researchregistry6430.

A systematic review and meta-analysis of the use of ultrasound to diagnose borderline ovarian tumours.

Borderline ovarian tumours (BOTs) are difficult to diagnose preoperatively. The ability to distinguish between BOTs and other ovarian cancer types prior to surgery could have a profound impact on patient childbearing counselling and surgical planning. Ultrasound (US) pattern recognition by an expert examiner can be an excellent tool for the discrimination of benign and malignant ovarian masses. With respect to US features, most studies were based on well-known risk models. Nevertheless, very few studies have solely evaluated the utility of ultrasound in diagnosing BOTs. We aimed to evaluate the use of US in identifying BOTs solely from benign and malignant ovarian tumours in isolation from risk models. We performed a systematic literature review to identify publications that evaluated the use of US to differentiate between BOTs and malignant and/or benign ovarian tumours using Pubmed, Web of Science and the Cochrane Library. We performed a meta-analysis of the diagnostic sensitivity and specificity studies. We computed the summary estimates for sensitivity and specificity of US in diagnosing BOTs using the bivariate approach of Reitsma in the mada package in R. The initial search resulted in 24,737 publications. Hundred and seven publications were screened, and five studies contained diagnostic data. Different US criteria applied to identify BOTs. Four out of five studies including 244 women with BOTs and 965 women with benign or malignant tumours were suitable for the meta-analysis. Pooling of the results from four studies showed an overall sensitivity of 0.660 (95 % CI: 0.597 - 0.718) and specificity of 0.854 (95 % CI: 0.728 - 0.927). The overall US accuracy was uniform in sensitivity and variable in specificity. A low false positive rate, 0.146 (95 % CI: 0.073 - 0.272) was observed. US correctly identified BOTs in more than six out of 10 women for potential ovarian sparing surgery, whereas it correctly identified the absence of BOTs in more than eight out of 10 symptomatic women. More carefully designed studies are needed to evaluate the use of pre-operative US for the diagnosis of BOTs.

Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial.

OBJECTIVE: Methotrexate is used routinely worldwide for the medical treatment of clinically stable women with a tubal ectopic pregnancy. This is despite the lack of robust evidence to show its superior effectiveness over expectant management. The aim of our multicenter randomized controlled trial was to compare success rates of methotrexate against placebo for the conservative treatment of tubal ectopic pregnancy. METHODS: This study took place in two early-pregnancy units in the UK between August 2005 and June 2014. Inclusion criteria were clinically stable women with a conclusive ultrasound diagnosis of a tubal ectopic pregnancy, presenting with a low serum beta human chorionic gonadotropin (ß-hCG) level of < 1500 IU/L. Women were assigned randomly to a single systemic injection of either 50 mg/m2 methotrexate or placebo. The primary outcome was a binary indicator for success of conservative management, defined as resolution of clinical symptoms and decline of serum ß-hCG to < 20 IU/L or a 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 of whom were assigned to methotrexate and 38 to placebo. The arms of the study were matched in terms of age, ethnicity, obstetric history, pregnancy characteristics and serum levels of ß-hCG and progesterone. The rates of success were similar for the two study arms: 83% with methotrexate and 76% with placebo. On univariate analysis, this difference was not statistically significant (χ2 (1 degree of freedom) = 0.53; P = 0.47). On multivariate logistic regression, the serum level of ß-hCG was the only covariate found to be significantly associated with outcome. The odds of failure increased by 0.15% for each unit increase in ß-hCG (odds ratio, 1.0015 (95% CI, 1.0002-1.003); P = 0.02). In 14 women presenting with serum ß-hCG of 1000-1500 IU/L, the success rate was 33% in those managed expectantly compared with 62% in those receiving methotrexate. This difference was not statistically significant and a larger sample size would be needed to give sufficient power to detect a difference in the subgroup of women with higher ß-hCG. In women with successful conservative treatment, there was no significant difference in median ß-hCG resolution times between study arms (17.5 (interquartile range (IQR), 14-28.0) days (n = 30) in the methotrexate group vs 14 (IQR, 7-29.5) days (n = 25) in the placebo group; P = 0.73). CONCLUSIONS: The results of our study do not support the routine use of methotrexate for the treatment of clinically stable women diagnosed with tubal ectopic pregnancy presenting with low serum ß-hCG (< 1500 IU/L). Further work is required to identify a subgroup of women with tubal ectopic pregnancy and ß-hCG ≥ 1500 IU/L in whom methotrexate may offer a safe and cost-effective alternative to surgery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Comparación entre una sola dosis de metotrexate sistémico y la conducta expectante en el tratamiento de casos de embarazo ectópico tubárico: un ensayo aleatorio controlado con placebo RESUMEN OBJETIVO: El metotrexate se utiliza de modo rutinario en todo el mundo para el tratamiento de las mujeres clínicamente estables con un embarazo ectópico tubárico. Esto sucede a pesar de la falta de evidencia rigurosa que demuestre que su eficacia es superior a la conducta expectante. El objetivo de este ensayo controlado aleatorio multicéntrico fue comparar las tasas de éxito del metotrexate con las de un placebo para el tratamiento cauteloso del embarazo ectópico tubárico. MÉTODOS: Este estudio se llevó a cabo en dos clínicas de control de gestación temprana en el Reino Unido entre agosto de 2005 y junio de 2014. Los criterios de inclusión fueron mujeres clínicamente estables con un diagnóstico ecográfico concluyente de embarazo ectópico tubárico, las cuáles presentaban una concentración sérica baja de la ß hormona coriónica gonadotrópica (ß-hCG) inferior a 1500 UI/L. Las mujeres fueron asignadas aleatoriamente a una sola inyección sistémica de 50 mg/m2 de metotrexate o a placebo. El resultado primario fue un indicador binario del éxito del tratamiento conservador, definido como la resolución de los síntomas clínicos y la disminución en el suero de la ß-hCG a <20 UI/L o una prueba de embarazo negativa en orina sin la necesidad de ninguna intervención médica adicional. Se hizo un análisis por intención de tratar. RESULTADOS: Se reclutó un total de 80 mujeres; a 42 de ellas se les asignó el metotrexate y a 38 el placebo. Los grupos del estudio se realizaron en función de la edad, el origen étnico, los antecedentes obstétricos, las características del embarazo y los niveles séricos de la ß-hCG y la progesterona. Las tasas de éxito fueron similares para los dos grupos de estudio: 83% con metotrexate y 76% con placebo. En el análisis univariante, esta diferencia no fue estadísticamente significativa (χ2 (1 grado de libertad) = 0,53; P = 0,47). En la regresión logística multivariante, el nivel sérico de la ß-hCG fue la única covariable que se encontró significativamente asociada con el resultado. Las probabilidades de fracaso aumentaron en un 0,15% por cada unidad de aumento de la ß-hCG (cociente de probabilidad 1,0015 (IC 95%, 1,0002-1,003); P = 0,02). La tasa de éxito en las 14 mujeres con un nivel sérico de la ß-hCG de 1000-1500 UI/L fue del 33% en las tratadas con conducta expectante frente al 62% en las que recibieron metotrexate. Esta diferencia no fue estadísticamente significativa, por lo que se necesitaría un tamaño de muestra mayor, lo suficiente como para poder detectar diferencias en el subgrupo de mujeres con una ß-hCG más elevada. En las mujeres en las que el tratamiento conservador tuvo éxito, no hubo una diferencia significativa en la mediana de los tiempos de resolución de la ß-hCG entre los grupos del estudio (17,5 (amplitud intercuartílica (IQR), 14-28,0) días (n = 30) en el grupo de metotrexate frente a 14 (IQR, 7-29.5) días (n = 25) en el grupo de placebo; P = 0,73). CONCLUSIONES: Los resultados de este estudio no apoyan el uso rutinario de metotrexate para el tratamiento de las mujeres clínicamente estables diagnosticadas con un embarazo ectópico tubárico que presenta un nivel sérico bajo la ß-hCG (<1500 UI/L). Serán necesarios estudios adicionales para identificar un subgrupo de mujeres con embarazo ectópico tubárico y ß-hCG ≥1500 UI/L para quienes el metotrexate puede ofrecer una alternativa segura y rentable en comparación con la cirugía. : : ,,。。 : 2005820146,2。,,ß(beta human chorionic gonadotropin,ß-hCG)<1500 IU/L。,(50 mg/m2 )。,ß-hCG<20 IU/L,。。 : 80,42,38。2、、、ß-hCG。2:83%,76%。,[χ2 (1)=0.53;P=0.47]。logistic,ß-hCG。ß-hCG,0.15%[,1.0015(95% CI,1.0002~1.003);P=0.02]。14ß-hCG1000~1500 IU/L,33%,62%。,ß-hCG。,2ß-hCG(P=0.73),17.5[(interquartile range,IQR),14~28.0](n=30),14 (IQR,7~29.5)(n=25)。 : 、、ß-hCG(<1500 IU/L)。,ß-hCG>1500 IU/L、。.