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Background: Ectopic pregnancies are a leading cause of maternal mortality. Most are treated surgically. We evaluated the efficacy and safety of combining oral gefitinib (epidermal growth factor receptor inhibitor) with methotrexate to treat larger ectopic pregnancies., Methods: We performed a phase II, single arm, open label study across four hospitals in Edinburgh and Melbourne. We recruited women with a stable tubal ectopic pregnancy and a pre-treatment serum hCG between 1000 and 10,000 IU/L. We administered intramuscular methotrexate (50 mg/m 2 ) once, and oral gefitinib (250 mg) for seven days. The primary outcome was the percentage successfully treated without needing surgery. To show the treatment is at least 70% effective, 28 participants were required, and 24 or more successfully treated without surgery. Secondary outcomes were safety, tolerability, and time to resolution. This study is registered (ACTRN12611001056987)., Findings: 30 participants with stable tubal ectopic pregnancies were recruited but two withdrew, leaving 28 participants. The median (± range) pre-treatment serum hCG was 2039 (1031-8575) IU/L and nine had pre-treatment hCGs levels >3000 IU/L. The treatment successfully resolved 86% (24/28) cases with a median (±range) time to resolution of 32 (18-67) days. The treatment caused transient rash and diarrhoea, but no serious adverse events., Interpretation: Combination gefitinib and methotrexate is at least 70% effective in resolving ectopic pregnancies with a pre-treatment serum hCG 1000-10,000 IU/L. This may be a new way to treat most stable ectopic pregnancies, but needs to be validated via a randomised clinical trial., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Objective: Incidence of molar pregnancy is 1-3/1000 pregnancies. Invasive mole is a local invasive form of gestational trophoblastic neoplasias which is mostly seen in reproductive age and usually follows a molar pregnancy and rarely has an initial presentation. Ectopic pregnancy in rudimentary uterine horn is extremely rare and is seen in 1/100,000 - 140,000 pregnancies. Invasive mole has seldom been reported in ectopic localizations but not in a patient with Müllerian duct anomaly. Here we represent a case of invasive mole in a reproductive age patient with unicornuate uterus and rudimentary communicating uterine horn. Invasive mole presented initially, mimicking ectopic pregnancy. The patient underwent diagnostic laparoscopy and resection of rudimentary uterine horn was performed. The pathology result was reported as an invasive mole. Serum b-hCG levels normalized on post-operative first month and no additional chemotherapy was needed., (© 2018 Old City Publishing, Inc.)

The aim of this study was to improve clinical decision-making for the identification of persistent ectopic pregnancy after linear salpingostomy. The study identified 854 laparoscopic salpingostomies performed between 2011 and 2016; 794 had a human chorionic gonadotrophin (HCG) <10 mIU/ml documented in the electronic medical record within 1 month after surgery ('successes'). Sixty (7%) received either methotrexate or repeat surgery for persistent ectopic pregnancy ('failures'). Five hundred and seventeen, including 46 'failures', had two or more immediate post-operative HCG measurements available. The most clinically useful prediction rule was calculated by dividing the difference between the first and second post-operative HCG values by the first post-operative HCG value (i.e. [HCG1 - HCG2]/HCG1). When this ratio exceeded 0.75, it reliably ruled out persistent ectopic with a negative predictive value = 99%. When this ratio was less than 0.2, it identified persistent ectopics with a positive predictive value = 88%. It appears that this simple arithmetic calculation involving two early post-operative HCG values may allow for efficient triage of patients before post-operative day 5. If validated in prospective studies, this could help minimize the risk, inconvenience and expense of requiring several weeks of frequent follow up to rule in/rule out persistent ectopic pregnancy., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Only 57 cases of ectopic pregnancy after hysterectomy have been published., Case Report: A 34-year-old patient with a history of subtotal hysterectomy for postpartum hemorrhage consulted for acute abdominal pain. The diagnosis of ectopic pregnancy was made using blood pregnancy test and transvaginal ultrasound. Emergency laparoscopy was performed., Conclusion: Urine pregnancy test should be performed in case of unexplained haemoperitoneum in patient of childbearing age with a history of hysterectomy. Fistulous tracts between the patent cervix or the vaginal cuff and the peritoneal cavity may allow fecundation. TEACHING POINTS: (1) Ectopic pregnancy remains a differential diagnosis of abdominal pain and haemoperitoneum in patient of childbearing age even after hysterectomy. (2) Fistulous tract between the residual cervix and the peritoneal cavity or tubes may allow fecundation., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the efficacy of ultrasound-guided local lauromacrogol injection combined with aspiration for treating cesarean scar pregnancy (CSP)., Methods: From July 2016 to December 2016, 18 patients diagnosed with CSP were treated with ultrasound-guided local lauromacrogol injection combined with aspiration. Clinical data and outcome were analysed., Results: All patients were treated successfully. The amount of bleeding ranged between 10 and 50 mL. The duration of hospitalization ranged between 2 and 11 days. Serum β-human chorionic gonadotropin (β-hCG) decreased to the nondetectable level within 19-41 days. Menstruation recovery occurred after 10-24 days of normalization of serum β-hCG level. Reproductive functions were preserved, and there were no untoward effects or complications., Conclusions: Ultrasound-guided local lauromacrogol injection combined with aspiration is an effective CSP therapy, as it was associated with a high success rate, short hospitalization and fast recovery. However, its wider application and popularization have to be validated on a larger patient population affected by CSP., (© 2017 S. Karger AG, Basel.)

Study Objective: To evaluate an alternative monitoring protocol without day 4 β-human chorionic gonadotropin (β-hCG) measurement for predicting the need for a repeated methotrexate (MTX) dose in patients undergoing single-dose MTX therapy for ectopic pregnancy (EP)., Design: Single-center retrospective study (Canadian Task Force classification II-3)., Setting: University-affiliated hospital., Patients: Included in the study were 184 EP patients treated with MTX between January 2009 and December 2016., Interventions: Single-dose MTX treatment (50 mg/m 2 )., Measurements and Main Results: The patients were treated with repeated doses of MTX every 7 days, if necessary, according to Stovall's protocol, or with laparoscopic surgery in cases of tubal rupture. The success of a single-dose of MTX according to the alternative measure was defined as a >50% decrease in the β-hCG level between days 1 and 7 in clinically stable patients. The sensitivity, specificity, false-negative rate, false-positive rate, and attributable risk of this new monitoring measure were calculated and compared with the traditional regimen. The new protocol had a sensitivity and specificity of 100% and 88.7%, respectively, for predicting a required second dose in patients whose day 1 β-hCG levels were <2000 mIU/mL. For patients with day 1 β-hCG level ≥2000 mIU/mL, both monitoring regimens had the same efficiency., Conclusions: The new monitoring model without the day 4 β-hCG measurement may offer both patients and clinicians multiple options to monitor single-dose MTX therapy for selected EP patients, with a comparable clinical efficiency to Stovall's protocol and less expense and follow-up burden to patients., (Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.)

Background: To investigate the use of uterine artery embolization (UAE) to manage ectopic pregnancies that are refractory to systemic methotrexate (MTX) therapy and plagued by persistently high serum β-human chorionic gonadotrophin (hCG) levels and vaginal bleeding. The safety and efficacy of UAE were addressed., Materials and Methods: A retrospective review was conducted for thirteen patients (mean age 35.2 years; range 28-41 years), who were treated between December 2006 and June 2016. Each was subjected to UAE due to persistently high serum β-hCG levels and vaginal bleeding after systemic MTX therapy for ectopic pregnancy. Embolic agents used were non-spherical polyvinyl alcohol or gelatin sponge particles. Post-treatment follow-up was performed by monitoring for clinical signs of vaginal bleeding, serum β-hCG testing, and transvaginal US. Outcomes were technical success, clinical success, and complications., Results: Median follow-up period was 172.5 days (range 30-600 days). Technical success was achieved in all 13 patients (100%). In 10 patients, vaginal bleeding resolved after one UAE attempt (clinical success 76.0%). Rebleeding in other three (23.1%) was controlled through repeat UAE. Seven patients (53.8%) had additional dilatation and curettage to remove gestational sac remnants. All ectopic pregnancies were successfully treated by UAE, with normalization of serum β-hCG levels during follow-up monitoring (P = 0.01). Uterine preservation was achieved in all 13 patients, without major procedural complications., Conclusion: UAE appears safe and effective as treatment of ectopic pregnancies marked by persistently high serum β-hCG levels and vaginal bleeding after systemic MTX treatment.

Objective: To validate whether change in serum HCG levels between days 0 and 4 confer any prognostic value during methotrexate therapy and to quantify its change., Study Design: This is a retrospective study of 48 tubal ectopic pregnancies treated with single dose methotrexate protocol at University Hospital, Muscat, Oman from January 2012 to December 2013. The clinical outcome was analyzed based on the complete resolution of HCG levels or need for additional doses of methotrexate or recourse to surgery. The percentage change in HCG levels between days 0 and 4 (HCG index) of methotrexate were calculated and receiver operator characteristics curve was plotted to identify the best cutoff levels. In order to get a robust 95% confidence interval, bootstrap method using R software was done using 1000 re-sampling. ROC curve and the predictive values were estimated using MEDCALC software., Results: The mean HCG level on day 4 is significantly higher in treatment failure group (4254±4095 IU/L vs. 2109±3646 IU/L, P=0.008). The HCG levels between day 0 and 4 decreased in 42.7% (21/48) of cases and 80.9% of these cases had treatment success. The HCG levels increased in 57.4% (27/48) of cases and 33.3% of these cases had treatment success. (P=0.001). A 10 percent decline in day 4 HCG levels predict the treatment success with sensitivity of 77% and Specificity 81%. The area under the ROC curve was 0.82 (95% CI: 0.67-0.92), (P<0.001)., Conclusion: The success with single dose of methotrexate therapy for tubal ectopic pregnancies was predicted early in the course of treatment by following three key findings: the absolute mean HCG values on day 4, decrease in HCG level from day 0 to 4 and 10% or more fall in day 4 HCG levels., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of the study was to compare the efficacy and safety between high-intensity focused ultrasound (HIFU) treatment and uterine artery embolization (UAE) treatment; we retrospectively analyzed 152 cases with cesarean scar pregnancy (CSP). Based on our inclusion and exclusion criteria, 152 patients (average age, 31.8 ± 4.6 years old) with CSP were eligible for the HIFU group (85 patients) or the UAE group (77 patients). All patients in 2 groups received the treatment with suction curettage under hysteroscopy prior to HIFU or UAE treatment and followed up for 12 months. The assessment criteria of treatment efficacy included the success rate, intraoperative blood loss, duration of vaginal bleeding, normal menstrual function recovery time, time for β-human chorionic gonadotrophin (β-HCG) back to normal level, duration of hospital stays, and other adverse effects. Following up for 12 months, the HIFU group was of less intraoperative blood loss (76.38 ± 22.89 vs 114.42 ± 30.34 mL, P = .02), shorter duration of postoperative vaginal bleeding (11.28 ± 3.65 vs 15.77 ± 7.24 days, P = .01) and lower adverse effects rate comparing to the UAE group. However, the HIFU group have longer time for the β-HCG recovery to the normal level (35.28 ± 9.86 vs 29.91 ± 7.29, P = .03). Additionally, there were no significantly statistic differences between the 2 groups in baseline characteristics, success rate, and average time of gestational sac disappeared and menstrual recovery and hospital stay. Thus, we concluded that the method of both HIFU and UAE combined with suction curettage under hysteroscopy is safe and effective in the management of CSP. Meanwhile, HIFU is a better therapy option than UAE for those women who are seeking complete relieve of symptom to gain fertility.

Objective: To evaluate the role HCG change in the 48h prior to methotrexate treatment as a predictor for treatment success., Study Design: Medical records of all women who were diagnosed with ectopic pregnancy between January 2001 and June 2013 were reviewed. Four hundred and nine patients received methotrexate due to ectopic pregnancy. The "single dose" methotrexate protocol with 50mg/m 2 was administered to patients with progressing ectopic pregnancy. HCG levels in days 1, 4 and 7 were used to evaluate methotrexate treatment success. The percentage of HCG change in the 48h prior to methotrexate treatment was compared between patients who were successfully treated and those who failed treatment with methotrexate., Results: Single dose methotrexate was successful in 309 patients (75.4%, success group). The medians of HCG change in the 48h prior to methotrexate administration were significantly higher in the "failure group" (21% vs. 4%, p<0.01). In a logistic regression analysis, the of HCG percent increment prior to methotrexate administration was shown to be an independent predictor for treatment outcome. Receiver operator characteristic curve for HCG percent change was 0.751, at a cutoff value of HCG increment <12% the positive predictive value for treatment success reached 86%., Conclusions: Percentage of HCG increment in the 48h prior to methotrexate administration is an independent predictor for methotrexate treatment success. HCG increment <12% prior to methotrexate treatment is a good predictor for treatment success., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Accurate diagnosis of ectopic pregnancy is essential in reducing maternal mortality and morbidity. Transvaginal ultrasound (TVUS) is the accepted imaging modality of choice for the diagnosis of ectopic pregnancy (EP)., Aims: To assess the effectiveness of transvaginal ultrasound (TVUS) in the detection of EP in consecutive women presenting for ultrasound to a radiology department with a clinical suspicion of EP., Methods: Retrospective analysis of 585 women presenting for TVUS over a 2.5-year period was performed. Women were classified as having a confirmed EP on the basis of surgery and histology. Women with a suspected EP who were treated medically or expectantly were also included., Results: Eighty-seven women had a confirmed EP and 29 women had a suspected EP. The sensitivity and specificity of ultrasound for the detection of confirmed EP was 88.5% and 96.5% on the initial TVUS and 93.1% and 95.7% with an additional rescan., Conclusion: TVUS in the radiology setting of a tertiary hospital has excellent diagnostic performance for the detection of EP., Competing Interests: Nil.

Aim: The aim of this study was to assay the clinical characteristics of persistent ectopic pregnancy (PEP) and its influence on ongoing pregnancy., Methods: We retrospectively reviewed 2498 patients who received salpingostomies as primary management for ectopic pregnancies from January 2004 to December 2009, using medical records and telephone inquiries. Clinical characteristics of the 52 patients (2.08%) who were diagnosed with PEP after salpingostomy were compared with those who received satisfactory treatment. The odds ratios and 95% confidential intervals were calculated for each variable by univariate and (for significantly different factors) multivariate analysis., Results: Preoperatively, patients with PEP after salpingostomy significantly differed from the non-PEP patients in gestational age, mass size and pelvic adhesiolysis. Serum β-human chorionic gonadotropin levels in PEP patients were monitored after surgery, which had declined by 28.31% on postoperative day (POD) 4, 40.22% on POD 7, 51.46% on POD 10 and 53.43% on POD 21. Repeat ectopic pregnancy (REP) tended to occur more frequently in PEP patients (PEP: 5 cases, 10.20%; non-PEP: 4 cases, 2.80%; P = 0.034). Multivariate analysis showed that pelvic adhesions and PEP were the strongest independent predictors of REP., Conclusion: Gestational age, mass size and pelvic adhesions were significantly correlated with PEP. PEP was an independent prognostic factor for REP. However, a multicenter study is needed to support and extend our findings., (© 2017 The Authors Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Purpose: The aim of this study is to investigate the clinical predictors of failure of a single dose of methotrexate (MTX) for management of ectopic pregnancy after in vitro fertilization (IVF)., Methods: A retrospective cohort study was performed of women who conceived ectopic pregnancies following fresh or frozen IVF cycles at an academic infertility clinic between 2007 and 2014, and received intramuscular MTX (50 mg/m 2 ). Successful single-dose MTX treatment was defined as a serum beta-human chorionic gonadotropin (hCG) decline ≥15% between days 4 and 7 post-treatment. Logistic regression models adjusted for oocyte age, number of embryos transferred, and prior ectopic pregnancy were used to estimate the adjusted odds ratio (OR) (95% confidence interval [CI]) of failing one dose of MTX., Results: Sixty-four patients with ectopic pregnancies after IVF were included. Forty required only one dose of MTX (62.5%), while 15 required additional MTX alone (up to four total doses, 23.4%), and 9 required surgery (14.1%). By multivariable logistic regression, the highest tertiles of serum hCG at peak (≥499 IU/L, OR = 9.73, CI 1.88-50.25) and at first MTX administration (≥342 IU/L, OR = 4.74, CI 1.11-20.26), fewer embryos transferred (OR = 0.37 per each additional embryo transferred, CI 0.19-0.74), and adnexal mass by ultrasound (OR = 3.65, CI 1.10-12.11) were each correlated with greater odds of requiring additional MTX and/or surgery., Conclusion: This is the first study to report that in women with ectopic pregnancies after IVF, higher hCG-though well below treatment failure thresholds previously described in spontaneous pregnancies-fewer embryos transferred, and adnexal masses are associated with greater odds of failing one dose of MTX. These findings can be used to counsel IVF patients regarding the likelihood of success with single-dose MTX.

Background: Surgical rescue of methotrexate-treated ectopic pregnancy is necessary when tubal rupture or medical therapy failure is detected during post-therapeutic monitoring. It is known that an increased beta human chorionic gonadotropin (β-hCG) concentration is the most important factor associated with treatment failure. Therefore, we suggested that relative changes in serum β-hCG could predict a successful result of medical treatment, leading to facilitation of the decision to forgo the prospect of possible surgical rescue., Methods: A retrospective observational study of 115 patients with an ectopic pregnancy who were treated with a single dosage protocol of 50mg/m 2 of methotrexate injected intramuscularly was performed at Puerta de Hierro University Hospital and Gregorio Marañón University General Hospital. Standard statistical tests were applied in order to evaluate the relative changes in β-hCG concentration between the 1st and the 4th days following methotrexate injection., Results: Methotrexate treatment has a 95% probability to be successful if the relative change of β-hCG from the 1st to the 4th day of monitoring is within the following interval: [-1.02; 0.15]. Moreover, if the values of β-hCG-relative change from 1st to 4th day of monitoring are within [0.54; 1.2], it assures a negative result of treatment with 95% probability. Therefore, the value 0.15 (15%) of β-hCG relative change can be considered a cut-off value for a positive result to treatment., Conclusions: Our data support that negative β-hCG relative changes on the 4th day of treatment likely predict a successful result of methotrexate therapy, with a cut-off point of 0.15. Expectant management should be carried out in these cases if no clinical indications of surgery are presented., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Evaluate whether morbid obesity influenced resolution, number of doses or ultimately surgical management of tubal ectopic pregnancy (TEP) when treated with single-dose regimen methotrexate (SDR-MTX) capped at 100 mg., Methods: Retrospective cohort study of patients with a diagnosis of TEP who underwent MTX treatment from 2000 to 2013. Patients were excluded if initial β-hCG <1000 mIU/mL, did not have β-hCG follow-up or were not treated with SDR-MTX. Per protocol, dose was administered at 50 mg/m 2 with a capped maximum of 100 mg. Patients were divided based on their BMI (<40 and ≥40 kg/m 2 ). Demographic variables, β-hCG before treatment, maximum diameter of ectopic size, embryonic heart tones, decrease of β-hCG, need for additional MTX doses and surgery despite treatment were recorded and compared among the groups., Results: 151 women were included in the study, 89.4% (135/151) non-morbidly obese and 10.6% (16/151) morbidly obese. No differences in age distribution, ethnicity, pre-treatment presence of embryonic heart tones, maximum diameter of ectopic size ≥35 mm and β-hCG ≥5000 mIU/ml were found. Following treatment, the proportion of patients with at least an 80% decrease in their β-hCG levels or need for surgery were similar, however, morbidly obese patients were significantly more likely [11/134 vs. 5/16, OR 5.1 (1.5-17.3, p = 0.015)] to require an additional MTX dose., Conclusion: Among patients with TEP, morbidly obese patients were five times more likely to require an additional dose compared to non-morbidly obese when SDR-MTX capped at 100 mg was used for medical management.

Objective: We sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort., Study Design: For this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure., Results: Between February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%., Conclusion: In this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Ectopic pregnancy (EP) refers to the implantation of the zygote outside the uterine cavity. In clinical practice, the diagnosis of EP relies on a combination of ultrasound findings and serum human chorionic gonadotrophin (hCG) measurements. However, the need for serial hCG measurements increases the risk of tubal rupture and death, underscoring the need to identify biomarkers for the early detection of EP., Methods: The serum concentrations of 21 microRNAs (miRNAs) associated with pregnancy or with known placental expression, as well as serum hCG and progesterone levels were analyzed 36 patients with viable intrauterine pregnancy (VIP), 30 patients with spontaneous abortion (SA), and 34 patients with EP using specific assay kits and reverse transcription PCR. The diagnostic performance of the different serum markers for detecting EP was analyzed by ROC curve analysis., Results: Five miRNAs were differentially expressed between the three groups, of which miR-873 and miR-223 were significantly lower in EP than in VIP and SA patients and did not change significantly according to gestational age, and miR-323 was significantly higher in EP than in VIP and SA. As a single marker, miR-873 had the highest sensitivity for detecting EP at 61.76% (at a fixed specificity of 90%). In comparison, the combination of hCG, progesterone and miR-873 had the highest sensitivity for detecting EP at 79.41% (at a fixed specificity of 90%)., Conclusion: Although further validation in large-scale prospective studies is necessary, our results suggest that miR-873 could be a valuable noninvasive and stable biomarker for the early detection of EP., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background: There are some theoretical concerns for the use of intraoperative cell salvage (ICS) in patients with ectopic pregnancy. This study aimed to observe the impact of ICS on the coagulation function and clinical outcomes of patients with ruptured ectopic pregnancy and severe blood loss., Methods: This was a retrospective study of 225 patients with ruptured ectopic pregnancy and severe blood loss treated at the Third Affiliated Hospital of Guangxi Medical University between January 2012 and May 2016. Patients were grouped according to ICS ( n = 116) and controls ( n = 109, allogenic transfusion and no transfusion)., Results: Compared with controls, patients with ICS had shorter hospitalization ( P = 0.007), lower requirement for allogenic blood products ( P < 0.001), and higher hemoglobin levels at discharge ( P < 0.001). There were no complications/ adverse reactions. In the ICS group, hemoglobin at discharge (-6.5%, P = 0.002) and thrombin time (-3.7%, P = 0.002) were decreased 24 h after surgery, while 24 h APTT was increased (+4.6%, P < 0.001). In the control group, hemoglobin at discharge (-16.8%, P < 0.001) was decreased after surgery and 24 h APTT was increased (+2.4%, P = 0.045). At discharge, hemoglobin levels were higher in the ICS group ( P < 0.001)., Conclusion: ICS was associated with good clinical outcomes in patients with ruptured ectopic pregnancy and severe blood loss.

Introduction: A broad ligament pregnancy is an extremely rare condition and diagnosis is frequently missed and finally made during laparotomy. This is a case of a young patient with high serum beta-human chorionic gonadotropin (β-hCG) levels after operation because of broad ligament pregnancy., Case Report: A 31-year-old multipara complained of intermittent lower abdominal pain with vaginal bleeding for four months. A color ultrasonography revealed a cystic mass in the left attachment area, indicating an interstitial tubal pregnancy. However, trophoblastic disease could not be excluded. She accepted conservative treatment with methotrexate (MTX) at first, but observation showed that conservative treatment was slow and accompanied with liver function damage. Therefore, exploratory laparotomy was performed. Intraoperative situations and postoperative pathology confirmed broad ligament pregnancy. Her serum p- hCG was sustained at a high level for three months after operation. Her examinations of serum, CT, and ultrasonography could explain this situation., Conclusion: Primary broad ligament pregnancy refers to pregnancy where implantation of the fertilized ovum occurs directly between the two leaves of the broad ligament. The gravid substance was removed, however serum β-hCG could not gradually re- turn to normal levels. This case should be followed-up closely to prevent adverse outcomes.

OBJECTIVE: To examine the potential use of hyperglycosylated human gonadotropin (hCG-H) in identifying ectopic pregnancies in pregnancies of unknown location (PULs) on ultrasound scan. STUDY DESIGN: This was a prospective observational study. An additional blood sample was taken from women whose initial transvaginal ultrasound scan showed none of the following: intact intrauterine pregnancy, retained placental tissue, or ectopic pregnancy. Parallel sandwich ELISAs were performed using sheep monoclonal antibodies to the 12F6 epitope for detection of total hCG and to the 4D8 epitope for hCG-H detection, and an automated immunoassay technique was used for progesterone and serum β-hCG measurements. Patients were managed accord-ing to our standard clinical protocol. RESULTS: hCG-H was significantly higher in ectopic pregnancies (85.6 ng/mL) than in viable intrauterine pregnancies (26.8 ng/mL) and spontaneously resolving pregnancies (23.2 ng/mL). The ability to distinguish ectopic pregnancies from nonectopic pregnancies, expressed as area under the curve, was 0.816 for hCG-H and 0.824 for total hCG. CONCLUSION: Women with an underlying ectopic pregnancy tended to have higher hCGs, whichever assay was used. However, the current study does not support a role for a single measurement of hCG-H in the diagnosis of ectopic pregnancy within the PUL population.

Objective: To report the results of local injection of diluted vasopressin followed by suction curettage as a conservative treatment for women with cervical ectopic pregnancy, who wish to preserve their future fertility., Study Design: This was a retrospective chart review in a university hospital and a municipal hospital. We injected diluted vasopressin (Pitressin R, total amount of 4-10 units) transvaginally into the cervix surrounding the gestational sac, but not directly into the gestational sac, and/or the lower segment of the uterine body under transvaginal ultrasonographic guidance. After cessation of fetal heartbeats, we aspirated the conceptus by performing suction curettage. We injected additional vasopressin into the gestational sac in cases with a viable fetus after the initial injection. Forced contraction of the cervical smooth muscle facilitated removal of the conceptus with minimal blood loss during curettage. We measured operative time, total blood loss, complications, and the need for additional treatment., Results: We included 11 women. Mean patient age, gestational age, and serum human chorionic gonadotrophin (hCG) at the intervention were 31.2±6.4years, 6.0±0.6 weeks, and 18,370±21,570 IU/L, respectively. Mean size of the gestational sac was 19.6±9.5mm. The uterus was successfully preserved without any complications in all patients. All procedures were completed within 15min except for the first case (range: 5-33min). In 4 cases, the conceptus containing a gestational sac was spontaneously extruded en bloc from the external os after the injection. Additional systematic methotrexate administration was required in one case because of remaining villi at the implantation site with persistence of serum hCG levels after the procedure., Conclusion: Local injection of diluted vasopressin and subsequent suction curettage is a feasible conservative treatment for cervical ectopic pregnancy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objective: To predict first trimester pregnancy outcome using biomarkers in a multicenter cohort., Design: Case-control study., Setting: Three academic centers., Patient(s): Women with pain and bleeding in early pregnancy., Intervention(s): Sera from women who were 5-12 weeks' gestational age with ectopic pregnancy (EP), viable intrauterine pregnancy (IUP), and miscarriage/spontaneous abortion (SAB) was analyzed by ELISA and immunoassay for activin A, inhibin A, P, A Disintegrin And Metalloprotease-12, pregnancy-associated plasma protein A (PAPP-A), pregnancy specific B 1 -glycoprotein (SP 1 ), placental-like growth factor, vascular endothelial growth factor, glycodelin (Glyc), and hCG. Classification trees were developed to optimize sensitivity/specificity for pregnancy location and viability., Main Outcome Measure(s): Area under receiver operating characteristic curve, sensitivity, specificity, and accuracy of first trimester pregnancy outcome., Result(s): In 230 pregnancies, the combination of trees to maximize sensitivity and specificity resulted in 73% specificity (95% confidence interval (CI) 0.65-0.80) and 31% sensitivity (95% CI 0.21-0.43) for viability. Similar methods had 21% sensitivity (95% CI 0.12-0.32) and 33% specificity (95% CI 0.26-0.41) for location. Activin A, Glyc, and A Disintegrin And Metalloprotease-12 definitively classified pregnancy location in 29% of the sample with 100% accuracy for EP. Progesterone and PAPP-A classified the viability in 61% of the sample with 94% accuracy., Conclusion(s): Multiple marker panels can distinguish pregnancy location and viability in a subset of women at risk for early pregnancy complications. This strategy of combining markers to maximize sensitivity and specificity results in high accuracy in a subset of subjects. Activin A, ADAM12, and Glyc are the most promising markers for pregnancy location; P and PAPP-A for viability., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: A uniform rationalized management protocol for pregnancies of unknown location (PUL) is lacking. We developed a two-step triage protocol to select PUL at high risk of ectopic pregnancy (EP), based on serum progesterone level at presentation (step 1) and the serum human chorionic gonadotropin (hCG) ratio, defined as the ratio of hCG at 48 h to hCG at presentation (step 2)., Methods: This was a cohort study of 2753 PUL (301 EP), involving a secondary analysis of prospectively and consecutively collected PUL data from two London-based university teaching hospitals. Using a chronological split we used 1449 PUL for development and 1304 for validation. We aimed to assign PUL as low risk with high confidence (high negative predictive value (NPV)) while classifying most EP as high risk (high sensitivity). The first triage step assigned PUL as low risk using a threshold of serum progesterone at presentation. The remaining PUL were triaged using a novel logistic regression risk model based on hCG ratio and initial serum progesterone (second step), defining low risk as an estimated EP risk of < 5%., Results: On validation, initial serum progesterone ≤ 2 nmol/L (step 1) classified 16.1% PUL as low risk. Second-step classification with the risk model selected an additional 46.0% of all PUL as low risk. Overall, the two-step protocol classified 62.1% of PUL as low risk, with an NPV of 98.6% and a sensitivity of 92.0%. When the risk model was used in isolation (i.e. without the first step), 60.5% of PUL were classified as low risk with 99.1% NPV and 94.9% sensitivity., Conclusion: PUL can be classified efficiently into being either high or low risk for complications using a two-step protocol involving initial progesterone and hCG levels and the hCG ratio. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Study Question: How do four protocols based on serial human chorionic gonadotropin (hCG) measurements perform when classifying pregnancies of unknown location (PULs) as low or high risk of being an ectopic pregnancy (EP)?, Summary Answer: The use of cut-offs in hCG level changes published by NICE, and a logistic regression model, M4, correctly classify more PULs as high risk, compared with two other protocols., What Is Known Already: A logistic regression model, M4, based on the mean of two consecutive hCG values and the hCG ratio (hCG 48 h/hCG 0 h) that classify PULs into low- and high-risk groups for triage purposes, identifies more EPs than a protocol using the cut-offs between a 13% decline and a 66% rise in hCG levels over 48 h., Study Design, Size, Duration: A retrospective comparative study of four different hCG-based protocols classifying PULs as low or high risk of being an EP was performed at a gynaecological emergency unit over 3 years., Participants/materials, Setting, Method: We identified 915 women with a PUL. Initial transvaginal ultrasonography (TVS) findings categorised 187 of the PULs as probable intrauterine pregnancies (IUPs) and 16 as probable EPs. The rate of change in hCG levels over 48 h was calculated for each patient and subjected to three different hCG threshold intervals and a logistic regression model for outcome prediction. Each PUL was subsequently dichotomised to either low-risk (i.e. failed PUL/IUP) or high-risk (i.e. EP) classification, which allowed us to compare the diagnostic performance. In 'Protocol A', a PUL was classified as low risk if >13% hCG level decline or >66% hCG level rise was achieved; otherwise, the PUL was classified as high risk of being an EP. 'Protocol B' classified a PUL as low or high risk using cut-offs of 35-50% declining hCG levels and of 53% rising hCG levels. Similarly, 'Protocol C' used hCG level cut-offs published by NICE, 50% for declining hCG levels and 63% for rising hCG levels. Finally, if a logistic regression model 'Protocol M4' calculated a ≥5% risk of the PUL being an EP, it was classified as high risk, and otherwise the PUL was classified as low risk. When the time interval between two hCG measurements failed to meet an exact 48 h, extrapolation and interpolation of hCG values was made, using log linear transformation., Main Results and the Role of Chance: Protocols A, B, C and M4 classified 73, 66, 55 and 56% of PULs as low risk. The sensitivity for protocols A, B, C and M4 was 68% (95% confidence interval (CI) 61-75%), 81% (74-86%), 87% (82-92%) and 88% (83-93%), respectively. The specificity was 82% (80-85%), 77% (74-80%), 66% (62-69%) and 67% (63-70%) for protocols A, B, C and M4, respectively. All comparisons of sensitivity and specificity between the protocols were statistically significant except for protocol C versus protocol M4. In protocol C, 87% (66-97%) of misclassified EPs had rising hCG levels, compared with 19% (6-41%) for protocol M4 (P < 0.01). In a secondary analysis excluding probable IUPs and probable EPs, the results for 712 PULs were analysed. The sensitivity subsequently remained stable for all protocols. Protocol M4 reached a 78% (74-81%) specificity, which was significantly higher than 70% (66-74%) for protocol C (P = 0.01) and protocol M4 classified 63% of PULs as low risk compared with 58% for protocol C., Limitations, Reasons for Caution: The retrospective design of the study is a limitation. The results are derived from a population where laparoscopy played an important role in PUL management and diagnosis of EPs, although it did reflect real clinical practice. Although we tried to adhere to definitions of PUL and final outcomes as in previous studies and a recent consensus statement, potential differences in this regard must be acknowledged. Where the time interval between two serial hCG measurements deviated from 48 h we estimated 48 h hCG values., Wider Implications of the Findings: A logistic regression model, M4, classifies more PULs correctly as low risk in a selected PUL population without probable IUPs and EPs and identifies as many EPs, in comparison with the cut-offs available in the NICE guideline. This advantage for model M4 may result in a reduction of unnecessary follow-up visits, when fewer low-risk PULs are misclassified as high risk. These findings, however, ought to be clarified in a randomised controlled trial., Study Funding/competing Interests: The study was supported by LUA/ALF grant No. 70940. There are no competing interests., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess whether variation in serum human chorionic gonadotropin (hCG) measures, used to assess early gestation viability, are associated with differences in clinical presentation and patient factors., Method: This retrospective cohort study included 285 women with first-trimester pain and bleeding and a pregnancy of unknown location for whom a normal intrauterine pregnancy was ultimately confirmed. Serial samples were collected at three U.S. sites and hCG changes were analyzed for differences by race, ethnicity, and clinical factors. A nonlinear, mixed-effects regression model was used assuming a random subject shift in the time axis., Results: The hCG rise in symptomatic women with ongoing intrauterine pregnancy differs by patient factors and level at presentation. The 2-day minimum (first percentile) rise in hCG was faster when presenting hCG values were low and slower when presenting hCG value was high. African American women had a faster hCG rise (P<.001) compared with non-African American women. Variation in hCG curves was associated with prior miscarriage (P=.014), presentation of bleeding (P<.001), and pain (P=.002). For initial hCG values of less than 1,500, 1,500-3,000 and greater than 3,000 milli-international units/mL, the predicted 2-day minimal (first percentile) rise was 49%, 40%, and 33%, respectively., Conclusion: The rise of hCG levels in women with viable intrauterine pregnancies and symptoms of potential pregnancy failure varies significantly by initial value. Changes in hCG rise related to race should not affect clinical care. To limit interruption of a potential desired intrauterine pregnancy, a more conservative "cutoff" (slower rise) is needed when hCG values are high., Clinical Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT00194168.

Study Objective: To evaluate the potential risk factors associated with failed ultrasound-guided dilation and curettage (D&C) treatment of cesarean scar pregnancy (CSP)., Design: Retrospective study., Setting: University hospital., Patients: Fifty-one patients diagnosed with CSP and treated with ultrasound-guided D&C at Shanghai General Hospital of Shanghai Jiao Tong University., Intervention: Lesion resection using ultrasound-guided D&C., Measurements and Main Results: Clinical characteristics, vaginal bleeding, abdominal pain, the size of the gestational sac, cardiac motion, blood flow around the gestational sac, cesarean scar thickness, and serum β-human chorionic gonadotropin (β-hCG) levels were compared between the successful operation group and the failed operation group. Cesarean scar thickness was the main risk factor that determined the success of ultrasound-guided D&C. The success rates were 50% and 97.67% for those with cesarean scars <3 mm thick and those with scars >3 mm thick, respectively (p = .001). The success rate was also associated with the abundance of blood flow surrounding the capsule and size of the gestational sac (p < .005). Surgical success was not affected by abnormal vaginal bleeding, abdominal pain, cardiac motion, or serum β-hCG levels., Conclusion: Ultrasound-guided D&C is the first choice for treating CSP if the cesarean scar is >3 mm thick, blood flow is not abundant, and the maximum diameter of the gestational sac is <30 mm. A transabdominal procedure is preferred for patients with high-risk factors., (Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.)

We aimed to investigate and compare the mean platelet volume (MPV) levels in ectopic and viable intrauterine pregnancy (IUP). The medical records of 78 unruptured tubal ectopic pregnancy patients (TEP, Group 1) and 150 patients with viable IUP (Group 2) served as control group between May 2014 and February 2015 in our clinic were retrospectively analysed. The demographic characteristics including age, parity, gravida, abortus, haemoglobin levels and leucocyte counts showed no statistically difference between two groups. The mean MPV level was significantly lower in TEP group compared to IUP group (8.69 ± 1.14 and 10.06 ± 1.46, p < 0.001). The platelet (PLT) distribution width was higher in TEP group, however, there was no statistical difference between the two groups (p = 0.078). The early diagnosis of TEP is crucial in order to prevent maternal morbidity and mortality. Our results showed that MPV is lower in TEP than IUP and it seems to be related with the possible inflammation at implantation site of tuba uterina. However, there is need for further studies for employing PLT indices in the diagnosis of TEP.

This case series describes changes in size, vascularity, and cul-de-sac fluid in 30 patients with ectopic pregnancies who were treated with systemic methotrexate. Pretreatment and posttreatment transvaginal sonography of the ectopic pregnancies was performed with color Doppler imaging, and the images were assessed for changes in size, vascularity, and cul-de-sac free fluid. There was a trend for nonresponders to show increased vascularity on serial examinations, although this finding was also seen in a single responder. There was also a trend for nonresponders with increased vascularity to be associated with a greater increase in β-human chorionic gonadotropin levels and responders with decreased vascularity to be associated with a greater decrease in β-human chorionic gonadotropin levels., (© 2016 by the American Institute of Ultrasound in Medicine.)

We evaluated the diagnostic accuracy of activin B in discriminating tubal ectopic pregnancy (tEP) from intrauterine miscarriages (IUM), and normal viable intrauterine pregnancy (IUP). We included 28 women with tEP, 31 women with IUM, and 29 normal IUP, confirmed both by clinical examination and ultrasonography. Serum activin B concentration was measured at the time of admission using the ELISA kit. The median serum activin B concentration was found to be significantly decreased in both tEP (p=0.004) and IUM (p=0.022) compared to normal IUP. When compared between tEP and IUM, activin B concentrations did not differ significantly. ROC analysis of activin B and free β-hCG demonstrated AUC of 0.722 and 0.805, respectively to discriminate tEP from viable IUP. The model including both activin B and free β-hCG improved the discriminating potential with greater AUC (0.824), and specificity (93%) than individual one. To discriminate tEP from IUM, activin B, free β-hCG and combination of both performed poorly. We conclude that serum activin B concentration is lower in tubal ectopic pregnancy, and can discriminate it from normal pregnancy with moderate accuracy. It also shows improved diagnostic potential along with free β-hCG, but cannot distinguish tEP from IUM reliably., (Copyright © 2016. Published by Elsevier Inc.)

Adnexal masses can have gynecologic or nongynecologic etiologies, ranging from normal luteal cysts to ovarian cancer to bowel abscesses. Women who report abdominal or pelvic pain, increased abdominal size or bloating, difficulty eating, or rapid satiety that occurs more than 12 times per month in less than a year should be evaluated for ovarian cancer. Pelvic examination has low sensitivity for detecting an adnexal mass; negative pelvic examination findings in a symptomatic woman should not deter further workup. Ectopic pregnancy must be ruled out in women of reproductive age. A cancer antigen 125 (CA 125) test may assist in the evaluation of an adnexal mass in appropriate patients. CA 125 levels are elevated in conditions other than ovarian cancer. Because substantial overlap in CA 125 levels between pre- and postmenopausal women may occur, this level alone is not recommended for differentiating between a benign and a malignant adnexal mass. Transvaginal ultrasonography is the first choice for imaging of an adnexal mass. Large mass size, complexity, projections, septation, irregularity, or bilaterality may indicate cancer. If disease is suspected outside of the ovary, computed tomography may be indicated; magnetic resonance imaging may better show malignant characteristics in the ovary. Serial ultrasonography and periodic measurement of CA 125 levels may help in differentiating between benign or potentially malignant adnexal masses. If an adnexal mass larger than 6 cm is found on ultrasonography, or if findings persist longer than 12 weeks, referral to a gynecologist or gynecologic oncologist is indicated.

Objective: To determine if the pattern of decline in hCG curves can discriminate spontaneous abortion (SAB) from ectopic pregnancy (EP)., Design: Retrospective cohort study., Setting: University hospitals., Patient(s): A total of 1,551 women with symptomatic pregnancy of unknown location (PUL) and decreasing hCG values., Intervention(s): None., Main Outcome Measure(s): Percentage change in hCG; days and visits to final diagnosis., Result(s): Of the 1,551 women with a PUL and declining hCG, 146 were ultimately diagnosed with EP and 1,405 with SAB. An 85% hCG drop within 4 days or a 95% hCG drop within 7 days both ruled out an EP 100% of the time. Applying the 4-day cutoff to this population would have saved 16% of the SAB population (229/1,405) a total of 2,841 person-days and 277 clinical visits. Applying the 7-day cutoff would have saved 9% of the SAB population (126/1,405) a total of 1,294 person-days and 182 clinical visits. These cutoffs were separately validated on a group of 179 EPs collected from three university clinical centers. In that population, each cutoff separately ruled out EP 100% of the time., Conclusion(s): The decline in serum hCG is slower in EPs than in SAB and can be used to aid clinicians in the frequency and duration of follow-up. Costs and patient time may be saved by allowing women who meet one of these criteria to be followed less frequently., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: There are only a few gynaecological departments in the Czech Republic that use medical treatment of the ectopic pregnancy (EP) or persistent pregnancy of unknown location (PUL). We have started using this method in 2008 at our clinic. The aim of this study was to assess the success rate of conservative medical treatment with methotrexate (MTX) in the dose of 1 mg/kg intramuscularly in patients with ectopic pregnancy or persistent pregnancy of unknown location and to compare the results of clinical history, clinical finding and laboratory results in a group of successful and a group of unsuccessful treatment., Type of Study: Retrospective analysis., Setting: Charles University in Prague, 1st Medical Faculty and Hospital Bulovka, Department of Obstetrics and Gynaecology, Prague., Methods: Patients diagnosed with EP or persistent PUL diagnosed at the outpatient of our clinic in 01/2008 - 08/2014 who were hemodynamically stable and fulfilled the indication for medical treatment were enrolled in the study. Treatment success was decrease of free subunit of β-hCG (β-hCG) < 5 IU/L independent of the number of methotrexate doses administered., Results: Two hundred and eleven patients were diagnosed with EP or PUL, sixty-three were eligible for our study and fulfilled the criteria for methotrexate treatment, fifty six women were finally analysed. From this number forty eight (86%) had clinically and laboratory diagnosed EP and eight (14%) were diagnosed with persistent PUL. Forty one patients (73%) had a successfull treatment (Group I) with the β-hCG level decrease <5 IU/L in a mean time of 27 days. When comparing the data of successful and unsuccessful treatment (Group II) we found a difference in the non-significant initial β-hCG level. In Group I there was a median β-hCG 538 IU/L (100-3852 IU/l), whereas in the unsuccessful Group II it was 1100 IU/L (300-3240 IU/l). Group I included more nuliparous women and more women with clinical histories of EP. Group II included more heavy smokers. The mean hematosalpinx diameter for group II, measured by transvaginal ultrasound, was larger. There were also more patients with endometriosis or deep infiltrating endometriosis in Group II, subsequently verified during laparoscopy, compared to Group I. There was no tubal rupture in these patients., Conclusion: The results of our study are comparable with foreign literature publications. We consider the pharmacological treatment of ectopic preganancy or persistent pregnancy of unknown location as effective and relatively safe for patients, with similar impact on a woman's fertility as laparoscopic salpingectomy.

Objective: To assess the occult pregnancy rate after "negative" first post-embryo transfer (ET) serum β-hCG results., Design: Two-part retrospective cohort study and nested case series., Setting: University-based fertility center., Patient(s): A total of 1,571 negative first post-ET serum β-hCG results were included in the study; 1,326 results (primary cohort, June 2009-December 2013) were initially reported as <5 mIU/mL and 245 results (secondary cohort, January 2014-March 2015) were reported as discrete values from 1.0 to 5.0 mIU/mL., Intervention(s): None., Main Outcome Measure(s): Rates of occult pregnancy, ectopic pregnancy, and complications after negative first post-ET serum β-hCG results., Result(s): A total of 88.8% (1,178/1,326) of the negative first post-ET results reported as <5 were actually <1.0 mIU/mL. Occult pregnancy was incidentally identified in 1.2% (12/1,041) of subjects with follow-up. Six had ectopic pregnancies, and seven experienced serious complications; 11 (91.7%) of the 12 occult pregnancies had a first post-ET serum β-hCG level of 1.0-5.0 mIU/mL and 1 (8.3%) <1.0 mIU/mL. All pregnancies with serious complications had initial β-hCG levels of 1.0-5.0 mIU/mL. Of the 245 results reported as discreet values, occult pregnancies were diagnosed in 5.5% (9/163) of subjects with follow-up. One had an ectopic pregnancy, which was treated with methotrexate. There were no serious complications in the secondary cohort., Conclusion(s): The majority of negative first post-ET serum β-hCG levels are <1.0 mIU/mL. Results from 1.0 to 5.0 mIU/mL may fail to exclude abnormal pregnancy and are associated with poor outcomes compared with β-hCG levels <1.0 mIU/mL. Serial serum β-hCG may be warranted in this population., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the ultrasound findings of ectopic pregnancy in the group of women examined in our department transvaginal ultrasound. Analysis of ectopic pregnancy cases covers the period from 1. 8. 2012. to 31. 9. 2015. We introduced several case studies., Design: Retrospective analysis., Setting: Department of Gynecology and Obstetrics, Hospital Jindrichuv Hradec., Methods: The methodology is based on a retrospective evaluation of the history, laboratory and ultrasound findings in a group of 30 patients with ectopic pregnancy., Results: At the first visit were diagnosed by transvaginal ultrasound 82% ectopic pregnancy. A patological adnexal mass was visualised in 84% cases. A negative ultrasound finding was observed in 16% cases. The results of our group of patients are more or less comparable with other studies. We recorded the same risk factors for ectopic pregnancy., Conclusion: Most ectopic pregnancies can be diagnosed at the first examination before starting treatment and treated at an early stage. Transvaginal ultrasound is the "gold standard" diagnostic tool of choice in the diagnosis of ectopic pregnancy in combination with the dynamics of serum levels β-hCG..

Early diagnosis of ectopic pregnancy (EP) is important due to life-threatening consequences in the first trimester of pregnancy. In this study we aimed to investigate the role of adenosine deaminase (ADA) activity in the prediction of EP. Forty-one patients with unruptured ectopic pregnancy comprised the case group and forty-two first trimester pregnant women with shown foetal heart beating in ultrasound comprised the control group. The mean ADA level in EP (10.9 ± 3.0 IU/L) was higher than that in control group (9.2 ± 3.6 IU/L) (p = 0.018). Receiver operating characteristics or ROC curve identified ADA value of 10.95 IU/L as optimal threshold for the prediction of EP with 56% sensitivity and 67% specificity. High ADA levels are valuable in the early diagnosis of EP. However more comprehensive studies are required.

Increased human chorionic gonadotropin levels (HCG) can be detected in femoral blood, bile, and vitreous humor collected during autopsy of pregnant women using a standard kit designed for living patients. In the study herein, the concentrations of HCG were measured in postmortem serum, vitreous, bile, cerebrospinal, and pericardial fluids in 4 cases of fatal ectopic pregnancy and 40 controls using a quantitative electrochemiluminescence immunoassay designed for living patients. No false-negative cases were identified in any of the analyzed samples in any of the ectopic pregnancy cases. No correlations were found between total HCG levels in postmortem serum and the other tested specimens. The results of this study would suggest that higher HCG in bile, vitreous, pericardial, and cerebrospinal fluids may confirm the existence of ectopic pregnancy and therefore identify other situations in which this hormone is increased, although gestational age cannot be reliably estimated using these values., (© 2015 American Academy of Forensic Sciences.)

Objective: The aim of the study was to evaluate the value of mean platelet volume (MPV) and neutrophil/lymphocyte ratio (NLR) to predict single-dose methotrexate (MTX) treatment success in ectopic pregnancy (EP)., Materials and Methods: A total of 115 EP diagnosed and hemodynamically stable women were enrolled in the study and divided into two groups as group 1, the treatment success group (n= 78) and group 2, the treatment failure group (n = 37). The authors compared the groups in terms of MPV and NLR., Results: MPV and NLR levels were higher in MTX treatment successful group than in failure group.The cut-off values of MPV and NLR were determined as 10.1 fL and 1.82, respectively. These cut off values showed similar sensitivity and specificity in prediction of MTX treat- ment success., Conclusion: MPV and NLR can be used as reliable markers to predict single-dose MTX treatment success however further studies are needed.

Background: Transfusion-related acute lung injury (TRALI) is a major cause of death associated with transfusion. Nevertheless it is still misdiagnosed and underreported. We present a case of this serious complication in order to make it more familiar to clinicians and indicate proper medical management, which is significant not only for the patients presenting TRALI symptoms but also for future recipients of blood components., Case Presentation: A 32-year-old white woman with in-vitro fertilization in anamnesis was admitted to Department of Obstetrics and Gynecology because of abdominal pain. Ultrasonography examination revealed pathological mass in left adnexa. The patient underwent laparoscopic left salpingectomy. The following day she reported progressive pain in lower abdomen with signs of peritoneal irritation. Emergency laparotomy was performed and active bleeding from fallopian tube was stopped. Four units of red blood cells concentrate and six units of fresh frozen plasma were transfused. Within two hours of surgery acute respiratory distress symptoms occurred, bilateral infiltrates were found on chest X-ray. The patient responded to supportive treatment (oxygen therapy, dexamethasone, diuretics) and her state improved within 12 hours. Serological diagnostics revealed anti-HLA antibodies in one donor which reacted with patient's granulocytes. Clinical picture and anti-leukocyte antibodies detected in blood component allowed to identify the immune-mediated TRALI., Conclusions: Transfusion-related acute lung injury is a life-threatening complication of transfusion which manifests as non-cardiogenic pulmonary edema. Each suspected case of this syndrome should be reported to blood center in order to confirm the diagnosis and implement preventive measures (exclusion of implicated donor from further blood donation).

Objective: The aim of the study was to determine the importance of β-hCG level on day 4 following methotrexate (MTX) administration, and the difference between β-hCG levels assessed on day 0 and day 4 in predicting treatment success., Material and Methods: A total of 68 women with tubal pregnancy, treated with a single dose of MTX, were selected for this retrospective study., Results: The success rate of single-dose MTX treatment in our clinic was 75% (51/68). Among 51 patients in whom MTX treatment was successful, 25 (36.8%) showed a decrease in β-hCG level of > 15% on days 0 and 4, and 44 (64.7%) showed a β-hCG level decrease of > 15% on days 4 and 7. For subjects with β-hCG decrease of > 15% on days 4 and 7, the standard error was 6.5%, and the area under the ROC curve was 81.7%, while the corresponding values for days 0 and 4 were 7.2% and 64%, respectively., Conclusions: A decrease of > 15 % in β-hCG levels between days 0 and 4 does not seem to be a better predictor for success of single-dose MTX treatment for ectopic pregnancy than between days 4 and 7. A statistically significant difference was observed only in β-hCG levels on day 7 in both, successful and unsuccessful single-dose MTX groups.

MicroRNAs represent nonprotein coding small RNA molecules that are very stable to degradation and responsible for gene silencing in most eukaryotic cells. Increased evidence has been accumulating over the years about their potential value as biomarkers for several diseases. MicroRNAs were predicted to be involved in nearly all biological processes from development to oncogenesis. In this review, we address the importance of circulating microRNAs in different conditions associated with pregnancy starting with the implantation period to preeclampsia and we shortly describe the correlation between placental circulating miRNAs and pregnancy status. We also discuss the importance of microRNAs in recurrent abortion and ectopic pregnancy.

Objective: To investigate whether interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1RA) serum levels in the early luteal phase differ in IVF cycles that result in an ectopic pregnancy (EP) when compared with other outcomes., Design: Retrospective cohort., Setting: Not applicable., Patient(s): A total of 307 women whose serum samples were available, with the following IVF outcomes: 103 live births, 80 negative pregnancy tests, 52 biochemical pregnancies, 47 EPs, and 25 miscarriages., Intervention(s): Serum samples were obtained on cycle days 24 and 28 (cycle day 14 = day of egg retrieval). Levels of IL-1β and IL-1RA were determined by quantitative ELISA performed by blinded personnel., Main Outcome Measure(s): IL-1β and IL-1RA levels, IL-1β-to-IL-1RA ratio versus cycle outcome., Result(s): The IL-1β levels were predictive of an EP. At cycle days 24 and 28 the mean IL-1β levels were higher in patients with an EP (127.1 pg/mL and 166.9 pg/mL, respectively) than in women with any other IVF outcome (15.8-55.3 pg/mL and 14.8-75.5 pg/mL, respectively). At cycle day 24 the IL-1β-to-IL-1RA ratio was 0.18 in the ectopic group versus 0.01-0.09 in the other groups., Conclusion(s): Elevated IL-1β levels and IL-1β-to-IL-1RA ratio as early as 4 days before the first pregnancy test are associated with an EP. If confirmed by prospective studies, clinical application of these findings could potentially improve EP detection., (Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the safety and effectiveness of conservative management for cervical ectopic pregnancies., Methods: We conducted a retrospective review of all cases of cervical ectopic pregnancy diagnosed at our tertiary care academic centre between January 2002 and July 2014. The diagnosis of cervical ectopic pregnancy was made using transvaginal ultrasound according to published criteria. Management decisions were made by individual clinicians., Results: Cervical ectopic pregnancy was diagnosed in 27 women with a median age of 34 years. Two thirds of them were nulliparous, and 44% (12/27) reported infertility. The mean gestational age at diagnosis was seven weeks. The median serum human chorionic gonadotropin level was 11 300 IU/L (range 610 to 163 700). Fetal cardiac activity was present in 19 pregnancies (70%). Vaginal bleeding was the most common presentation, occurring in 23 cases (85%). Three women presented with acute life-threatening hemorrhage. All cases were successfully managed conservatively, allowing uterine preservation. Systemic methotrexate (single or multi-dose protocol) was the mainstay of therapy. Other minimally invasive interventions included ultrasound-guided injection of potassium chloride into the pregnancy, uterine artery embolization, vaginal ligation of cervical branches of the uterine arteries, and dilatation and curettage, with or without dilute vasopressin cervical infiltration and Foley catheter tamponade., Conclusion: Systemic methotrexate alone or in combination with other minimally invasive techniques can be effective conservative treatment for cervical pregnancies. A fertility-sparing approach is the optimal treatment for this patient population, which has high rates of infertility and nulliparity. We present a management algorithm based on our results to aid in standardizing the management of cervical ectopic pregnancies.

Since being introduced more than 30 years ago, endovaginal ultrasonography (US) and quantitative testing of serum levels of the beta subunit of human chorionic gonadotropin have become the standard means of establishing the presence of normal intrauterine pregnancy (IUP), failed IUP, and ectopic pregnancy. Appropriate use of these powerful tools requires clear, standardized interpretations based on conservative criteria to protect both the pregnancy and the mother. Since diagnoses are assigned earlier and available medical treatments for ectopic pregnancy and failed IUP are expanding, emphasis must carefully shift toward watchful waiting when the mother is clinically stable and a definitive location for the pregnancy cannot be established with US. To this end and to prevent inadvertent harm to early normal pregnancies, the Society of Radiologists in Ultrasound convened a consensus panel of radiologists, obstetricians, and emergency medicine physicians in 2012 with the goal of reviewing current literature and clinical practices and formulating modern criteria and terminology for the various first-trimester outcomes., ((©)RSNA, 2015.)

Objective: To analyze the plasmatic ADM level in early pregnancy and to investigate the diagnostic value of ADM in early ectopic pregnancy (EP)., Methods: 70 patients with EP who had menopause for 5~8 weeks were included as study group, while 155 women with normal intrauterine pregnancy were also included as control group. The correlation between ADM level and menopause weeks was statistically analyzed and ROC curve was used to identify the diagnostic value of ADM., Results: (1) In 155 cases of normal intrauterine pregnancy, the plasmatic ADM level was increased with menopause weeks in linear relationship, and the correlation coefficient (R) was 0.991 (P<0.05). In 70 patients with EP, no significant increase was found with menopause weeks and no linear relationship can be found between ADM level and menopause weeks in EP group. The correlation coefficient (R) was 0.744 (P>0.05). (2) The multiple of median of plasmatic ADM level in EP group of menopause for 8 weeks was obviously lower than the intrauterine control group (P<0.01). (3) ROC curve was used to analyze the cut-off value of ADM level in the diagnosis of EP, and the area under the ROC curve was 0.523 (P>0.05) regardless of menopause weeks, however, the area under the ROC curve was 0.702 (P<0.05) at 8 weeks after menopause with sensitivity of 53.50% and specificity of 85.00%., Conclusions: Different from normal intrauterine pregnancy, plasmatic ADM level in early EP was relatively lower and no significant increase was found with menopause weeks; further studies are still needed for plasmatic ADM level as an indicator in the early diagnosis of EP.

Objective: To find out the outcome of a cohort of women with pregnancy of unknown location presenting to a tertiary care hospital., Methods: The prospective study was conducted from January to December, 2011, at Early Pregnancy Assessment Unit, King Faisal Military Hospital, Khamis Mushait, Saudi Arabia. Data was collected for women with early pregnancy or with history of amenorrhoea, bleeding or pain. These women were investigated with serum beta-human chorionic gonadotrophin levels twice weekly and transvaginal ultrasonography weekly. Expectant management was done for failing pregnancy of unknown location while medical or surgical management was considered for persistent pregnancy of unknown location and ectopic pregnancy., Results: During study period, 7215 patients were admitted, and, of them, 2212(30.6%) were patients with early pregnancy. Meeting the inclusion criteria were 183(2.53%) patients who formed the study sample. There were 131(71.6%) patients presenting with amenorrhoea, 90(49.2%) had bleeding and 93(50.8%) presented with pain. Outcome of 100(54.6%) patients was failing pregnancy of unknown location, 58(31.7%) had intrauterine pregnancy, 14(7.7%) converted to ectopic pregnancy, while 11(6%) had persistent pregnancy of unknown location. All patients with persistent pregnancy of unknown location and 5(36%) patients with ectopic pregnancy were medically treated. Five (36%) patients having ectopic pregnancy were managed surgically., Conclusions: Management of choice for asymptomatic patients having pregnancy of unknown location is expectant management. Most of the patients suspected to have Most of the patients with persistent pregnancy of unknown location and ectopic pregnancy can be managed medically.

In this case-control study, we investigated the seroprevalence and molecular evidence of Chlamydia trachomatis and Waddlia chondrophila in ectopic pregnancies (EP) and uneventful control pregnancies in 343 women from Vietnam. Whereas presence of C. trachomatis IgG was strongly associated with EP [adjusted odds ratio (aOR) 5·41, 95% confidence interval (CI) 2·58-11·32], its DNA remained undetected in all tubal lesions. We confirmed an independent association between antibodies against Waddlia and previous miscarriage (aOR 1·87, 95% CI 1·02-3·42). Further investigations are needed to understand the clinical significance of Waddlia's high seroprevalence (25·9% in control pregnancies) in this urban population.