Search

Purpose: This study was presented to investigate the clinical-pathological characteristics of gestational trophoblastic neoplasia (GTN) following non-molar pregnancy and differentiated with ectopic pregnancy (EP)., Methods: The clinical data of 83 patients who were admitted for suspected GTN after non-molar pregnancy at the Women's Hospital School of Medicine Zhejiang University from January 2015 to September 2022 were selected for analysis., Results: In total, 41 cases were confirmed non-molar GTN, including 31 choriocarcinoma, 9 PSTT (placental site trophoblastic tumor), and 1 ETT (epithelioid trophoblastic tumor), while 42 cases were confirmed EP. Compared with ectopic pregnancy, non-molar GTN patients had lower levels of serum progesterone compared with EP (3.81 nmol/L vs 17.70 nmol/L, P = 0.001). Based on the ultrasound, the thickness of the endometrium was thinner in patients with non-molar GTN compared with EP (0.565 cm vs 0.70 cm, P = 0.018). By histopathologic examination, the endothelium of non-molar GTN showed less decidual-like changes compared with EP (64.3% vs 14.6%, P = 0.001)., Conclusion: A combination of serum progesterone levels, endometrium thickness, and histopathologic features of the endometrium can help to differentiate non-molar GTN and EP. Surgeries including hysteroscopy with curettage and/or laparoscopy are needed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: This study's aim is to investigate whether the rise in β-hCG levels between days 0 and 4 in patients with tubal ectopic pregnancy who have received a single dose of methotrexate has prognostic value in treatment success, and to investigate whether administering a second dose on day 4 enhances treatment success., Material and Methods: Patients diagnosed with ectopic pregnancy and experiencing an increase in β- hCG levels on day 4 after initiation of methotrexate treatment were included in our study. Patients treated with a single dose Methotrexate (MTX) protocol until December 2019 were retrospectively screened from January 2018 to December 2019. Patients receiving a second dose on day 4 until September 2021 were prospectively enrolled from January 2020 to September 2021. A decrease of over 15 % in the β-hCG value after the 4th dose was considered as treatment success., Results: Treatment success rates were compared between these two groups. 115 patients with ectopic pregnancy were included in the study. A single dose methotrexate protocol was applied in 67 of the patients (Group 1), while an additional dose methotrexate was applied in 48 (Group 2). The treatment was successful in 40 patients (59.7 %) in Group 1 and in 39 patients (81.3 %) in Group 2. The success rate of the treatment was significantly higher in patients who received an additional dose methotrexate protocol (p = 0.014)., Discussion: This study shows that; it is possible to increase success rates by applying an additional MTX dose on the 4th day in cases with an increase in β-hCG on the 4th day., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Problem: Cesarean scar pregnancy (CSP) is characterized by a gestational sac fully or partially implanted in the scar from a previous cesarean section. Systemic immune-inflammation indices (SIIs) have recently been discussed as additional diagnostic markers in placenta accreta and preeclampsia. CSP shares a similar pathogenesis with these diseases, suggesting that assessing the SIIs and neutrophil-to-lymphocyte ratio (NLR) could enhance additional predictability in diagnosing CSP., Method of Study: In this study, we analyzed the complete blood counts between 264 women who were confirmed with CSP by ultrasound and 295 women who underwent elective termination., Results: The mean counts of total white cells and neutrophils were significantly higher, whereas the counts of monocytes, lymphocytes, and platelets were significantly lower in the CSP group compared to the control group (p < 0.001). Additionally, the SII, systemic inflammation response index (SIRI), or NLR was significantly higher in the CSP group compared to the control group (p < 0.0001). Given the limited effect of SII and SIRI on the increased risk of developing CSP, the optimal cut-off value for NLR in predicting CSP was 2.87 (area under the curve [AUC] 0.656, 68% sensitivity). The optimal cut-off value for NLR in predicting type 2 CSP was 2.91 (AUC 0.690, 71% sensitivity)., Conclusions: Although ultrasound or magnetic resonance imaging images are a gold standard for visualizing the gestational sac's location in the diagnosis of CSP, assessing peripheral blood tests is cost-effective, and NLR may provide additional diagnosis value for CSP., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate combinations of candidate biomarkers to develop a multiplexed prediction model for identifying the viability and location of an early pregnancy. In this study, we assessed 24 biomarkers with multiple machine learning-based methodologies to assess if multiplexed biomarkers may improve the diagnosis of normal and abnormal early pregnancies., Design: A nested case-control design evaluated the predictive ability and discrimination of biomarkers in patients at risk of early pregnancy failure in the first trimester to classify viability and location., Setting: Three university hospitals., Patients: A total of 218 individuals with pain and/or bleeding in early pregnancy: 75 had an ongoing intrauterine gestation; 68 had ectopic pregnancies (EPs); and 75 had miscarriages., Interventions: Serum levels of 24 biomarkers were assessed in the same patients. Multiple machine learning-based methodologies to evaluate combinations of these top candidates to develop a multiplexed prediction model for the identification of a nonviable pregnancy (ongoing intrauterine pregnancy vs. miscarriage or EP) and an EP (EP vs. ongoing intrauterine pregnancy or miscarriage)., Main Outcome Measures: The predicted classification using each model was compared with the actual diagnosis, and sensitivity, specificity, positive predictive value, negative predictive value, conclusive classification, and accuracy were calculated., Results: Models using classification regression tree analysis using 3 (pregnancy-specific beta-1-glycoprotein 3 [PSG3], chorionic gonadotropin-alpha subunit, and pregnancy-associated plasma protein-A) biomarkers were able to predict a maximum sensitivity of 93.3% and a maximum specificity of 98.6%. The model with the highest accuracy was 97.4% (with 70.2% receiving classification). Models using an overlapping group of 3 (soluble fms-like tyrosine kinase-1, PSG3, and tissue factor pathway inhibitor 2) biomarkers achieved a maximum sensitivity of 98.5% and a maximum specificity of 95.3%. The model with the highest accuracy was 94.4% (with 65.6% receiving classification). When the models were used simultaneously, the conclusive classification increased to 72.7% with an accuracy of 95.9%. The predictive ability of the biomarkers in the random forest produced similar test characteristics when using 11 predictive biomarkers., Conclusion: We have demonstrated a pool of biomarkers from divergent biological pathways that can be used to classify individuals with potential early pregnancy loss. The biomarkers choriogonadotropin alpha, pregnancy-associated plasma protein-A, and PSG3 can be used to predict viability, and soluble fms-like tyrosine kinase-1, tissue factor pathway inhibitor 2, and PSG3 can be used to predict pregnancy location., Competing Interests: Declaration of Interests K.T.B. reports funding from NIH R01HD076279 and NIH ROI HD 110448 for the submitted work; funding from NIH ROI HD 110448 and NIH R01HD076279; patent pending outside the submitted work. K.J.B. has nothing to disclose. S.S. reports funding from National Institutes of Health, AbbVie, and Burroughs Wellcome Fund; Society for Assisted Reproductive Technology Research Committee Chair; Oncofertility Consortium Practice Committee outside the submitted work. P.T. reports funding from NIH ROI HD 110448 for the submitted work. J.C.R. has nothing to disclose. D.J.H. has nothing to disclose. L.A.B. has nothing to disclose. R.F.S. has nothing to disclose. N.C.K. has nothing to disclose. D.W.S. has nothing to disclose. J.C. has nothing to disclose. J.B. has nothing to disclose. Z.W. has nothing to disclose. Y.F. has nothing to disclose. M.K. reports funding from National research foundation of Korea; honorarium from Catholic university of Korea. S.M. reports funding from National Institutes of Health (UG3-OD035537) and PCORI (BPS-2022C3-30268); travel support from Society for Epidemiologic Research; Society for Epidemiologic Research Member at Large of the Executive Committee outside the submitted work. L.S. reports funding from R01 HD110448 for the submitted work; funding from IIS 1837964 RF1 AG063481 R01 LM013463 U01 AG068057 R01 AG058854 R01 AG071470 RF1 AG068191 U01 AG066833 R01 AG066833 P30 AG073105 R01 LM011176 - 09 R01 LM011176 - 09S1 R01 LM011176 - 09S2 R00 HG010905 R01 HD110448 U19 AG074879 LillyLRAP P30AG073105-03S2 outside the submitted work. P.G. has nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To evaluate the efficacy of two different regimens of Letrozole, an aromatase inhibitor, in the management of ectopic pregnancy compared to methotrexate., Study Design: This randomized controlled trial was conducted on 88 women diagnosed with ectopic pregnancy with a baseline level of serum beta-human chorionic gonadotropin under 3000 mIU/mL between June 30, 2023, and December 30, 2023, at the Department of Obstetrics and Gynecology of the Vali-e-Asr Hospital affiliated with Tehran University of Medical Sciences. Participants were allocated into either methotrexate (n = 43), 5-day course Letrozole (n = 24), or 10-day course Letrozole (n = 21) treatments. The methotrexate group received a single dose of 50 mg/m 2 dosage intramuscular methotrexate. The 5-day Letrozole group received a 2.5 mg Letrozole tablet three times daily for 5 days, whereas the 10-day Letrozole group received a 2.5 mg Letrozole tablet twice daily for 10 days. The primary outcome was the treatment response, defined as the achievement of a negative serum beta-human chorionic level without the need for additional methotrexate treatment or surgery. The secondary outcomes were the need for additional methotrexate dose or laparoscopic surgery intervention. The trial protocol was prospectively registered in ClinicalTrials.gov with code NCT05918718., Results: The treatment response rates in methotrexate, 5-day Letrozole, and 10-day Letrozole groups were 76.7 %, 75.0 %, and 90.5 %, respectively, with no significant differences between the groups (P-value = 0.358). A total of 10 (23.3 %) patients from the methotrexate group, 3 (12.5 %) from the 5-day Letrozole group, and 2 (9.5 %) from the 10-day Letrozole group required an additional methotrexate dose, with no significant differences between the groups (P-value = 0.307). Furthermore, only 3 (12.5 %) patients, all from the 5-day Letrozole group, were suspected of tubal rupture and underwent surgery (P-value = 0.016)., Conclusion: Our findings suggest Letrozole as a safe alternative to methotrexate in treating stable ectopic pregnancies, with a favorable treatment response rate. However, there is still a need for future larger studies to determine the applicability of Letrozole in the EP management. Also, the non-significant higher effectiveness of the 10-day Letrozole regimen than the 5-day Letrozole group underscores the need for future research to determine the optimal Letrozole regimen for the management of ectopic pregnancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: This work aimed to explore the relationship between epidermal growth factor (EGF) and β-human chorionic gonadotropin (β-HCG) and ectopic pregnancy types and impact on prognosis., Methods: Twenty women with normal pregnancies (NPs) were recruited as control group, and twenty women each with tubal pregnancy (TP) and cervical pregnancy (CP) were recruited. Blood samples were collected to detect EGF and β-HCG. Data on length of hospital stay and incidence of complications were collected. The differences in serum EGF and β-HCG levels were compared among groups and within various types of ectopic pregnancy using analysis of variance and Pearson correlation analysis., Results: Serum EGF and β-HCG were notably lower in TP and CP group vs. controls (P < 0.05). In subgroup analysis within the types of ectopic pregnancy, serum EGF levels were drastically higher in TP group vs. CP group (P < 0.05). Serum EGF levels were negatively correlated with pregnancy outcomes and incidence of complications (P < 0.05). In patients with TP and CP, serum EGF and β-HCG recovery time and hospital stay differed drastically (P < 0.05). Serum EGF and β-HCG levels showed optimal cutoff values identified at 2.65 μg/L and 11,745.35 IU/L, respectively. The corresponding area under the curve (AUC) values were 0.885 and 0.841., Conclusion: Elevated levels of EGF may be associated with the occurrence of ectopic pregnancy and may impact the type of ectopic pregnancy, pregnancy outcomes, and the incidence of complications. Further clinical research is warranted to investigate these findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the association of the Systemic Immune-Inflammation Index (SII), Systemic Immune-Response Index (SIRI), and Neutrophil-to-Lymphocyte Ratio (NLR) with Cesarean Scar Pregnancy (CSP) METHODS: This prospective case-control study was conducted in Ankara City Hospital perinatology clinic between 2022 and 2023. The diagnosis of CSP was made by transabdominal and transvaginal ultrasound. NLR, SII, and SIRI values were compared between those diagnosed with CSP (n=23) and healthy pregnancies (n=126) at the time of first admission., Results: The study group had significantly higher NLR, SII, and SIRI values compared to the controls. Optimal cut-off values were 3.79 (69 % sensitivity, 78.2 % specificity), 1180.6 (76.7 % sensitivity, 72.7 % specificity), and, 1.9 (83.3 % sensitivity, 72.7 % specificity) for NLR, SII, and SIRI, respectively. When NLR, SII and SIRI values were compared between CSP cases and pregnant women who had previous history of cesarean section but did not have CSP, significantly higher SII values were observed in the CSP group. The optimal cut-off value of SII was found to be 804.4 in predicting CSP among cases with previous history of cesarean delivery (73.9 % sensitivity, 66.2 % specificity)., Conclusion: SII, SIRI, and NLR may be useful in predicting cesarean scar pregnancy in pregnant women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: The objective of the study was to increase the prediction of success of single-dose methotrexate therapy in ectopic pregnancy patients with modified parameters obtained from complete blood count and beta-human chorionic gonadotropin (β-hCG) parameters. In this way, it was aimed to predict patients whose methotrexate treatment may fail and rupture, to avoid unnecessary methotrexate treatment, to shorten the duration of hospital stay and to reduce patient mortality., Materials and Methods: 233 patients diagnosed with ectopic pregnancy between January 1, 2017, and March 01, 2022, in the obstetrics and gynecology service of a tertiary center were included in the study., Results: The mean of β-hCG was 1976 in the methotrexate group and 2358 in the surgery group (p < 0.05). The ROC curve determined the effect of BW (β-hCGxWBC/1000) and BP (β-hCGx1000/PLT) markers in diagnosing patients who will need surgery in ectopic pregnancy. The areas under the ROC curve for β-hCG, BW and BP were 0.86, 0.99 and 0.94, respectively (p < 0.05). β-hCG > 2139.03, BW > 30.96 and BP > 10.17 values were significantly associated with the need for surgery in ectopic pregnancy patients (p < 0.05). Logistic regression analysis revealed that a 1-unit increase in BP caused a statistically significant 1.77-fold increase in surgical need in patients with ectopic pregnancy. In contrast, a 1-unit increase in BW caused a 2.34-fold increase in surgical need (p < 0.05)., Conclusion: The study results showed that BW and BP values together with β-hCG are effective in predicting ectopic pregnancy patients who may undergo surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A significant number of pregnancies are lost in the first trimester and 1-2% are ectopic pregnancies (EPs). Early pregnancy loss in general can cause significant morbidity with bleeding or infection, while EPs are the leading cause of maternal mortality in the first trimester. Symptoms of pregnancy loss and EP are very similar (including pain and bleeding); however, these symptoms are also common in live normally sited pregnancies (LNSP). To date, no biomarkers have been identified to differentiate LNSP from pregnancies that will not progress beyond early gestation (non-viable or EPs), defined together as combined adverse outcomes (CAO). In this study, we present a novel machine learning pipeline to create prediction models that identify a composite biomarker to differentiate LNSP from CAO in symptomatic women. This prospective cohort study included 370 participants. A single blood sample was prospectively collected from participants on first emergency presentation prior to final clinical diagnosis of pregnancy outcome: LNSP, miscarriage, pregnancy of unknown location (PUL) or tubal EP (tEP). Miscarriage, PUL and tEP were grouped together into a CAO group. Human chorionic gonadotrophin β (β-hCG) and progesterone concentrations were measured in plasma. Serum samples were subjected to untargeted metabolomic profiling. The cohort was randomly split into train and validation data sets, with the train data set subjected to variable selection. Nine metabolite signals were identified as key discriminators of LNSP versus CAO. Random forest models were constructed using stable metabolite signals alone, or in combination with plasma hormone concentrations and demographic data. When comparing LNSP with CAO, a model with stable metabolite signals only demonstrated a modest predictive accuracy (0.68), which was comparable to a model of β-hCG and progesterone (0.71). The best model for LNSP prediction comprised stable metabolite signals and hormone concentrations (accuracy = 0.79). In conclusion, serum metabolite levels and biochemical markers from a single blood sample possess modest predictive utility in differentiating LNSP from CAO pregnancies upon first presentation, which is improved by variable selection and combination using machine learning. A diagnostic test to confirm LNSP and thus exclude pregnancies affecting maternal morbidity and potentially life-threatening outcomes would be invaluable in emergency situations., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Aim: Methotrexate has demonstrated efficacy in treating ectopic pregnancies. This study explores factors influencing treatment success, focusing on laboratory and ultrasonographic findings, particularly the day 4 to day 1 β-hCG level ratio., Methods: Retrospective cohort study was conducted within patients diagnosed with tubal ectopic pregnancy. Patients' characteristics, ultrasound findings, laboratory data, and β-hCG levels (days 1, 4, 7), and operation findings were reviewed. Women's characteristics were investigated who were treated with single dose of MTX (50 mg/m 2 ). Patients who were performed surgery after MTX treatment were identified as MTX treatment failure., Results: Among 439 women, 259 underwent surgery due to acute symptoms. Of those treated with MTX, 143 experienced treatment success, while 37 underwent surgery after MTX (MTX failure). Comparative analysis revealed significant differences in β-hCG levels on admission (1128 and 4125 mIU/mL) and the day 4 to day 1 β-hCG ratio (0.91 and 1.25). The overall MTX success rate was 79%, reaching 93% and 89% for β-hCG levels <1000 mIU/mL and <2000 mIU/mL, respectively. Success dropped to 50% with levels exceeding 5000 mIU/mL. ROC analysis identified a crucial 2255 mIU/mL cut-off for β-hCG (sensitivity 70.3% and specificity 68.5%) and a day 4 to day 1 β-hCG ratio of 95.5% (sensitivity 84.7%, specificity 72.5%, positive predictive value 75.4%) for predicting MTX success., Conclusion: Establishing a β-hCG cutoff can reduce hospital stay. The day 4 to day 1 β-hCG ratio holds promise as a widely applicable predictor for MTX success or for determining MTX administration on day 4., (© 2024 Japan Society of Obstetrics and Gynecology.)

Introduction: Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic gonadotropin (β-hCG) level to qualify for diagnostic testing (pelvic ultrasound) can delay diagnosis and treatment. In this study we sought to determine the relationship between β-hCG level and the size of ectopic pregnancy with associated outcomes., Methods: We performed a retrospective case review of patients diagnosed with ectopic pregnancy in an urban, academic emergency department specializing in obstetrical care, from January 1, 2015-December 31, 2017. Variables extracted included presentation, treatment, adverse outcomes, and rates of rupture., Results: We identified 519 unique ectopic pregnancies. Of those ectopic pregnancies, 22.9% presented with evidence of rupture on ultrasound, and 14.4% showed evidence of hemodynamic instability (pulse >100 beats per minute; systolic blood pressure <90 millimeters of mercury; or evidence of significant blood loss) on presentation. Medical management outcomes were as follows: of 177 patients who received single-dose methotrexate, 14.7% failed medical management and required surgical intervention; of 46 who received multi-dose methotrexate, 36.9% failed medical management and required surgical intervention. Ultimately, 55.7% of patients required operative management of their ectopic pregnancy. Mean β-hCG level at initial presentation was 7,096 milli-international units per milliliter (mIU/mL) (SD 88,872 mIU/mL) with a median of 1,289 mIU/mL; 50.4% of ectopic pregnancies presented with β-hCG levels less than the standard discriminatory zone of 1,500 mIU/mL. Additionally, 44% of the patients who presented with evidence of rupture had β-hCG levels less than 1,500 mIU/mL. Comparison of size of ectopic pregnancy (based on maximum dimension in millimeters) to β-hCG levels revealed a very weak correlation (r = 0.144, P  < .001 ), and detection of ectopic pregnancies by ultrasound was independent of β-hCG levels., Conclusion: Levels of β-hCG do not correlate with the presence or size of an ectopic pregnancy, indicating need for diagnostic imaging regardless of β-hCG level in patients with clinical suspicion for ectopic pregnancy. Almost one-sixth of patients presented with evidence of hemodynamic instability, and approximately one quarter of patients presented with evidence of rupture requiring emergent operative management. Ultimately, more than half of patients required an operative procedure to definitively manage their ectopic pregnancy., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.

Introduction: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and β human chorionic gonadotropin (βhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, βhCG, and βhCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location., Material and Methods: This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial βhCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, βhCG, and βhCG ratio., Results: Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for βhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had βhCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single βhCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the βhCG ratio. Although the median βhCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2 nmol/L and βhCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation., Conclusions: Cut-off levels for βhCG, βhCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although βhCG ratio and progesterone have slightly better performance in comparison, single βhCG used in this manner is highly unreliable., (© 2021 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To describe and compare the characteristics of ectopic pregnancies (EPs) in the year prior to vs during the coronavirus disease 2019 (COVID-19) pandemic., Methods: This was a retrospective analysis of women diagnosed with an EP on transvaginal sonography conducted at a center in London, UK, providing early-pregnancy assessment, between 1 January 2019 and 31 December 2020. Women were identified via the Astraia ultrasound reporting system using coded and non-coded outcomes of EP or pregnancy outside the uterine cavity. Data related to predefined outcomes were collected using Astraia and Cerner electronic reporting systems. Main outcome measures included clinical, ultrasound and biochemical features of EP, in addition to reported complications and management., Results: There were 22 683 consultations over the 2-year period. Following consultation, a similar number and proportion of EPs were diagnosed in 2019 (141/12 657 (1%)) and 2020 (134/10 026 (1%)). Both cohorts were comparable in age, ethnicity, weight and method of conception. Gestational age at the first transvaginal sonography scan and at diagnosis were similar, and no difference in location, size or morphology of EP was found between the two cohorts. Serum human chorionic gonadotropin (hCG) levels at the time of EP diagnosis were higher in 2020 than in 2019 (1005 IU/L vs 665 IU/L; P = 0.03). The proportions of women according to type of final EP management were similar, but the rate of failed first-line management was higher during vs before the pandemic (16% vs 6%; P = 0.01). The rates of blood detected in the pelvis (hemoperitoneum) on ultrasound (23% vs 26%; P = 0.58) and of ruptured EP confirmed surgically (9% vs 3%; P = 0.07) were similar in 2019 vs 2020., Conclusions: No difference was observed in the location, size, morphology or gestational age at the first ultrasound examination or at diagnosis of EP between women diagnosed before vs during the COVID-19 pandemic. Complication rates and final management strategy were also unchanged. However, hCG levels and the failure rate of first-line conservative management measures were higher during the pandemic. Our findings suggest that women continued to access appropriate care for EP during the COVID-19 pandemic, with no evidence of diagnostic delay or an increase in adverse outcome in our population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: The aim of this study was to investigate the thiol/disulfide homeostasis in tubal ectopic pregnancies in terms of early diagnosis of the disease., Design: A prospective case-control study was carried out between June 2017-February 2018 in the Gynaecology Department of Umraniye Medical and Research Hospital., Materials and Methods: A total of 42 women with ectopic pregnancy were compared with 44 healthy women who have intrauterine first trimester pregnancies. The thiol/disulfide homeostasis is evaluated with the spectrophotometric measurement method that was recently developed by Erel&Neselioglu., Results: Disulfide/native thiol and disulfide/total thiol ratios were increased (p = 0.018 and p = 0.023 respectively), while native thiol/total thiol ratios and native thiol levels were decreased in tubal ectopic pregnancy group according to control group (p = 0.023). Between control and tubal ectopic pregnancy groups no differences were measured in disulfide levels (p = 0.350). The area under curve for native thiol and total thiol were 0.937 and 0.927, respectively. The optimum cut off value for native thiol was 379.95 μmol/l with a sensitivity of 90% and specificity of 81%. The optimum cut off value for total thiol was 432.5 μmol/l had 92% sensitivity and 79% specificity., Limitations: In the study, whether intrauterine pregnancies resulted in miscarriage or delivery can be examined., Conclusion: Increased disulfide/native thiol levels, disulfide/total-thiol ratio and decreased native/total thiol ratio were found to be significantly associated with the presence of tubal ectopic pregnancy which can be useful for the early diagnosis of the disease., Competing Interests: Conflict of Interest Statement The authors have nothing to declare., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Purpose: Ectopic pregnancy is a condition of enormous gynaecological priority. It occurs when fertilized ovum implants outside the uterine cavity. Ectopic pregnancy is estimated to be 1-2% of all-natural conception. This study aims to evaluate the role of the placental growth factor in the diagnosis of ectopic pregnancy., Methods: A case-control study was conducted in (Baghdad) teaching hospital in (Baghdad, Iraq) over one year. The study includes 240 women: 120 women with first trimester (5-10) weeks viable intrauterine pregnancy, and 120 women with ectopic pregnancy., Results: There is a significant association observed in the placental growth factor mean (PLGF), which is lower in ectopic pregnancy than in intrauterine pregnancy. The range of PLGF was less than 50 pg/mL in ectopic pregnancy, while it was up to 800 pg/mL in intrauterine pregnancy. In an ectopic pregnancy with a cut-off PLGF level of ≤ 15.5 pg/mL, the PLGF had a sensitivity of (92.5%), a specificity of (82.5%), a positive predictive value of (91.8%), a negative predictive value of (83.5%), and an accuracy of (90%). Different factors can affect PLGF, like the parity and body mass index., Conclusion: The serum level of the placental growth factor seems to be a promising biomarker for diagnosing ectopic pregnancy because a highly significant difference was found between healthy and ectopic pregnancy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To investigate published cases of cervical ectopic pregnancy between 2000 and 2018 and compare management strategies and treatment success rates based on initial patient characteristics., Methods: PubMed, EMBASE, and Web of Science were searched to capture peer-reviewed citations published between 2000 and 2018. Cases reporting either β-hCG level, crown-rump length, or gestational sac diameter for each individual patient were included. Data regarding the article information, patient characteristics, treatment used, and outcomes were collected. Initial success was defined as resolution of the cervical ectopic pregnancy with the predefined treatment plan. Initial failure was defined as the requirement of additional unplanned interventions due to the predefined treatment plan not being successful. End success was defined as resolution of the cervical ectopic pregnancy without hysterectomy., Results: A total of 204 articles from 44 countries comprising 454 cases were reviewed. The initial β-hCG level ranged from 9 to 286,500, with a median of 14,773, and gestational age ranged from 4 to 18 weeks, with an average of 7 4/7 weeks (±2 0/7 weeks). In looking at initial success, compared with methotrexate alone, dilation, and curettage (odds ratio [OR] 2.26; 95% CI 2.64-10.45), dilation and curettage combined with uterine artery embolization (OR 4.85; 95% CI 2.06-11.44) and uterine artery embolization (OR 5.17; 95% CI 1.14-23.53) were more effective options. More than half of patients (50.2%) required multiple interventions, and 41 (9%) resulted in hysterectomy., Conclusions: Management of cervical ectopic pregnancies should be guided by patient stability, β-hCG level, size of pregnancy, and fetal cardiac activity but may benefit from a planned multimodal approach., Competing Interests: Financial Disclosure Katharine White reports that money was paid to her institution by Bayer and Merck. She received funds from Fitbit Inc. and Mithra Pharmaceuticals (grant support to the institution). The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to investigate characteristics associated with ectopic pregnancy (EP) that could be utilized for predicting morbidity or mortality., Methods: This was a retrospective analysis of pregnancy-related records from a tertiary center over a period of ten years. Data on age, gravidity, parity, EP risk, amenorrhea duration, abdominal pain presence and location, β-human chorionic gonadotropin (β-HCG) level, ultrasound findings, therapeutic intervention, exact EP implantation site and length of hospital stay (LOS) were obtained from the database. The LOS was used as a proxy for morbidity and was tested for an association with all variables. All statistical analyses were conducted with Stata® (ver. 16.1, Texas, USA)., Results: The incidence of EP in a cohort of 30,247 pregnancies over a ten-year period was 1.05%. Patients presented with lower abdominal pain in 87.9% of cases, and the likelihood of experiencing pain was tenfold higher if fluid was detectable in the pouch of Douglas. Only 5.1% of patients had a detectable embryonic heartbeat, and 18.15% had one or more risk factors for EP. While most EPs were tubal, 2% were ovarian. The LOS was 1.9 days, and laparoscopic intervention was the main management procedure. The cohort included one genetically proven dizygotic heterotopic pregnancy (incidence, 3.3 × 10 - 5 ) that was diagnosed in the 7th gestational week. The only association found was between the β-HCG level and LOS, with a linear regression β coefficient of 0.01 and a P-value of 0.04., Conclusion: EP is a relatively common condition affecting approximately 1% of all pregnancies. β-HCG correlates with EP-related morbidity, but the overall morbidity rate of EP is low regardless of the implantation site. Laparoscopic surgery is an effective therapeutic procedure that is safe for managing EP, even in cases of heterotopic pregnancy.

Introduction: We investigated whether temporary bilateral laparoscopic uterine artery clipping with hysteroscopic transcervical resection (LUA clipping-TCR) is an effective minimally invasive treatment for the management of cervical pregnancy., Materials and Methods: This study is a retrospective clinical case series conducted at Teine Keijinkai Hospital from January 2014 to June 2019. Nine cervical pregnancies among 164 ectopic pregnancies were retrospectively examined. The intervention involved performing LUA clipping-TCR on villous tissue. Information on patient characteristics, clinical data, and surgical details was collected from medical records and surgical videos., Results: The mean (range) age of the patients was 33 years (29-41 years); and mean gestational sac diameter, 12.8 mm (5-24 mm). Five patients had a history of intrauterine procedures. Three patients had a positive fetal heartbeat. The mean (range) preoperative serum hCG level (mIU/mL), surgical time (min), uterine artery blocking time (min), and amount of surgical blood loss (ml) were 14,040 (2880-41,367), 82 (62-120), 42 (21-68), and 57 (10-200), respectively. The mean decrease in serum hCG level (second postoperative day) and duration until resumption of menstruation were 79.7 % (70-86.7 %) and 46 days (35-80 days), respectively. The hospitalization period was 2-3 days, with no evidence of persistent ectopic pregnancy. Live birth was achieved in four cases., Discussion: Our results confirm previous findings and provide new evidence that LUA clipping-TCR is effective for cervical pregnancy management and fertility preservation, respectively. Future large-scale prospective studies to compare different cervical pregnancy management methods are required., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: We aimed to present two cases of cesarean scar pregnancy (CSP) and a literature review to discuss their management., Cases: We reported two cases of cesarean scar pregnancy (CSP) treated in Strasbourg's University Hospital between 2016 and 2018 and carried out an updated literature review concerning their treatment., Results: The first case is a superficial implantation CSP managed by methotrexate (MTX) then ligation of the uterine arteries and echo-guided aspiration. The second case is a deep implantation CSP managed by MTX and then laparoscopic excision with clamping of the uterine arteries. In the literature, the most commonly used treatments are: MTX, echo-guided aspiration, and the combination of uterine artery embolization followed by echo-guided aspiration., Conclusion: We established an algorithm in which CSP treatment by MTX can be considered alone if criteria are met. If not, surgery, chosen according to the depth of implantation, will be associated with MTX with a preventive hemostasis procedure by embolization or ligation of the uterine arteries., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Purpose: The present systematic review aimed to examine the relationship between lung neoplasm and human chorionic gonadotropin (HCG). Especially, women with lung neoplasm mimicking as ectopic pregnancy were explored., Methods: A rare case of lung neoplasm with high serum β-HCG, which was initially thought to be ectopic pregnancy, was reported. A literature search was performed of the US National Library of Medicine (MEDLINE), EMBASE, PubMed, and the Cochrane Database of Systematic Reviews using appropriate keywords and subject headings to February 2020., Results: Studies assessed lung neoplasm patients with positive HCG were included. Twenty studies, including 24 patients, were included. These cases illustrate the importance of considering the possibility of paraneoplastic secretion of β-HCG in patients who have a positive pregnancy test. This may prevent a delay in the diagnosis and treatment of malignancy in young women. Of the 24 cases, only 7 (29.17%) were managed surgically; others were managed conservatively or with chemotherapy or radiation., Conclusion: The present systematic review shows the need to re-awaken awareness and high index of suspicion to lung neoplasm diagnosis in patients with positive pregnancy test.

Cesarean scar pregnancy (CSP) is a rare occurrence consisting in the implantation of the embryo within the myometrium of a prior cesarean delivery scar. The CSP could be a dangerous condition for women because of the related complications such as placenta previa or accreta, uterine rupture, and hemorrhage. Therefore, early diagnosis and rapid treatment are crucial. Extrauterine implants or ectopic pregnancy (EP) consists in the implantation of an embryo in a site other than the endometrium of the uterine cavity. It occurs in 1%-2% of all reported pregnancies. The most common extrauterine location is the fallopian tube, which represents 96% of cases. The diagnosis of CSP and EP is based on history, clinical examination, levels of serum β-human chorionic gonadotropin (β-hCG), and ultrasonography findings. In last 20 years, new treatments were developed, varying from medical management, minimally invasive surgical approach and local treatment including systemic or local infusion of metotrexate (MTX), and uterine artery embolization (UAE). UAE has been used widely to control hemorrhage and preserve the uterus and it is considered an affective adjuvant treatment of CSP and EP, especially associated with other therapies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Ectopic pregnancy is a major life- and fertility-threatening women's health concern. As a result of advances in examination technology, an increasing number of ectopic pregnancies can be diagnosed early and treated with medical methods instead of surgery. The aim of this study was to summarize the clinical features and identify the predictors of success of methotrexate (MTX) treatment of ectopic pregnancy., Methods: This was a retrospective study of 238 ectopic pregnancies treated with MTX in the Department of Gynecology of Shaanxi Provincial People's Hospital from January 2017 to December 2017., Results: Patients were divided into two groups: the successful treatment group (n = 166) and the failed treatment group (n = 72). The overall success rate of MTX therapy for ectopic pregnancy was 69.75%. The mean initial beta-human chorionic gonadotropin (β-hCG) level was significantly lower in the successful treatment group than in the failed treatment group (2538.08 IU/L versus 3533.17 IU/L, P = 0.000). The treatment success rate of the group with an initial β-hCG concentration less than 4000 IU/L was significantly higher than that of the group with an initial β-hCG concentration greater than 4000 IU/L. However, the success rate of the group with an initial β-hCG concentration greater than 4000 IU/L was still relatively high (54.55%). β-hCG levels were significantly increased on the 4th day in the failed treatment group (P = 0.000). Compared to the initial β-hCG level, the day-4 β-hCG level increased by more than 8.21%, indicating that the treatment was effective. The diagnostic sensitivity was 88.6%, the specificity was 74.5%, and the area under the receiver operating characteristic (ROC) curve was 0.863 (95% confidence interval (CI): 0.805-0.920)., Conclusions: MTX therapy as a treatment option is safe and effective for asymptomatic, hemodynamically stable patients with ectopic pregnancies who are interested in conservative treatment, regardless of the serum β-hCG level or adnexal mass size. The change in the β-hCG level between the initial day and the 4th day is an effective and early predictive tool for the success of MTX therapy for ectopic pregnancy.

Coronavirus disease 2019 (COVID-19) is a novel type of highly contagious pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the strong efforts taken to control the epidemic, hundreds of thousands of people were infected worldwide by 11 March, and the situation was characterized as a pandemic by the World Health Organization. Pregnant women are more susceptible to viral infection due to immune and anatomic alteration, though hospital visits may increase the chance of infection, the lack of medical care during pregnancy may do more harm. Hence, a well-managed system that allows pregnant women to access maternal health care with minimum exposure risk is desired during the outbreak. Here, we present the managing processes of three pregnant women who had fever during hospitalization in the gynecology or obstetrics department, and then, we further summarize and demonstrate our maternal health care management strategies including antenatal care planning, patient triage based on the risk level, admission control, and measures counteracting emergencies and newly discovered high-risk cases at in-patient department. In the meantime, we will explain the alterations we have done throughout different stages of the epidemic and also review relative articles in both Chinese and English to compare our strategies with those of other areas. Although tens of COVID-19 cases were confirmed in our hospital, no nosocomial infection has occurred and none of the pregnant women registered in our hospital was reported to be infected., (© 2020 Wiley Periodicals, Inc.)

Objective: To evaluate the role of β-HCG level changes between days 0 and 1 as an early predictor of methotrexate success in cases of tubal ectopic pregnancy. Methods: A retrospective study included 86 tubal ectopic pregnancies treated with a single-dose methotrexate protocol of 50 mg/m 2 of body surface. β-HCG measurements were taken on days 0, 1, 4 and 7 where day 0 is the day of methotrexate injection. Day 0 β-HCG and the percentage change in β-HCG level between days 0 and 1 (HCG index) were calculated and compared between patients who were successfully or unsuccessfully treated. Receiver operator characteristics (ROC) curves were plotted to identify the best cutoff levels. Results: The average level of β-HCG (1416.8 versus 2502.5 IU/L, p =.001) and its increment after 24 hours (12.9 versus 27.1%, p =.001) were significantly lower in the successful treatment group. ROC curves for β-HCG level and its relative increment revealed that cutoff values of ≤1550 IU/L and ≤13% increment showed a sensitivity of 90 and 70% respectively for successful methotrexate treatment. Conclusion: Day 0 β-HCG level ≤1550 IU/L and an increment of ≤13% after 24 hours are early predictors of successful methotrexate treatment for tubal ectopic pregnancy.

Design: From July 2016 to June 2018, 36 women with symptomatic early pregnancy around 4-8 weeks of gestation were recruited into the study. Among them, there were 16 women with viable intrauterine pregnancy (VIP), 9 women with spontaneous abortion (SA), and 11 women of EP. Serum exosomal miRNAs were extracted and measured at the first prenatal visit. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP., Results: Concentrations of miR-378d in serum exosomes were significantly higher in EP than in VIP and also SA group. As a single marker, miR-378d had the highest specificity of 64% at the sensitivity of 89.1%. Comparatively, both combined panels of hCG, progesterone, miR-100-5p and hCG, progesterone, and miR-215-5P yielded the specificity of 96%. Panels for all markers achieved the highest specificity of 80% at the sensitivity of 91%., Conclusions: Although further validation in large-scale prospective studies is necessary, our results suggest that serum exosomal miR-378d, miR-100-5p, and miR-215-5P are promising biomarkers for early EP., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jianhua Sun et al.)

Aim: Cervical pregnancy (CP) and cesarean scar pregnancy (CSP), defined as low-lying-implantation ectopic pregnancy (LLIEP), are rare conditions of aberrant implantation around the lowest portion of the uterus. This study aimed to illustrate the serum β-human chorionic gonadotropin (β-hCG) profile of LLIEP and to explore its implications with the clinical characteristics., Methods: Women with LLIEP during the first trimester were retrospectively evaluated at a tertiary referral center from August 1999 to July 2016. Demographic and clinical data were recorded, including maternal age, gestational age (GA), serum β-hCG level, maximal diameter of the gestational mass/sac (MDM/MDS) by ultrasonography and CSP implantation types. The serum β-hCG level was measured on the day of ultrasound imaging. The significance of pretreatment the serum β-hCG level and its correlations with the clinical characteristics were analyzed., Results: A total of 88 LLIEP with 64 CSP and 24 CP was included. The mean GA at the time of diagnosis was 7 weeks (range, 5-12 weeks). The β-hCG concentrations rapidly increased from GA 5 to 9 weeks and fluctuated thereafter. The β-hCG levels correlated positively with GA and ultrasound MDM/MDS. In the CSP group, there was no difference in the β-hCG level between superficial and deep implantation types. β-hCG levels demonstrated no significant differences among simple and complicated LLIEP., Conclusion: This study established the serum β-hCG profile in LLIEP in the first trimester. The exponential increase of β-hCG levels was similar to that of normal intrauterine pregnancies. The β-hCG levels were not associated with placentation complexity of CSP. Higher β-hCG levels did not implicate less success in conservative surgical management., (© 2020 Japan Society of Obstetrics and Gynecology.)

A circulating biomarker of early pregnancy outcome independent of ultrasonography and gestational age is a coveted goal. This study evaluated soluble urokinase plasminogen activator receptor (suPAR), a well-described marker of inflammation and immunological activation, for this purpose, and compared it with established early pregnancy biomarkers of the luteoplacental phase: progesterone, estradiol and hCG. We merged data from two prospective first trimester cohorts to conduct a case-control study comparing these analytes in women who had either a live birth, a miscarriage or an ectopic pregnancy. The ability to predict pregnancy location and viability was assessed by areas under the receiver operating characteristic curves (AUC). Comparing women irrespective of gestational age with a live birth, miscarriage or ectopic pregnancy showed significantly lower suPAR values in the latter group (2.4 vs. 2.4 vs. 2.0 μg/L, p = 0.032, respectively), as were all other analytes. Before 6 weeks' gestation, suPAR was significantly inferior to progesterone, estradiol and hCG in pregnancy location and viability prediction (in 124 pregnancies, suPAR AUC location = 0.69 [CI: 0.54-0.83] and AUC viability = 0.58 [CI: 0.48-0.69], while progesterone AUC location = 0.95 [CI: 0.87-1.00] and AUC viability = 0.84 [CI: 0.75-0.92]). After 6 weeks' gestation, suPAR prediction improved but was inferior to hCG, progesterone and estradiol (in 188 pregnanices, suPAR AUC location = 0.71 [CI: 0.63-0.78] and AUC viability = 0.70 [CI: 0.63-0.78] compared with hCG AUC location = 0.96 [CI: 0.93-0.99] and AUC viability = 0.96 [CI: 0.93-0.98]). Collectively, suPAR is less useful as a predictor of early pregnancy outcome than hCG, progesterone and estradol., Competing Interests: Declaration of Competing Interest Outside the submitted work Anders Nyboe Andersen reports grants and personal fees from Ferring, MSD and Gedeon-Richter and personal fees and honoraria from Merck Serono, MSD, Novo-Nordisk and Abbott. All other authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Local injection of methotrexate (MTX) has been widely used for caesarean scar pregnancy (CSP), but the optimal candidate remains undetermined. The aim of this study is to determine the risk factors associated with treatment failure among patients who received a single dose of local MTX. This is a retrospective cohort study. Clinical information was compared between treatment success vs. failure groups. Risk factors related to treatment failure were also investigated with multivariate analysis. Of 47 patients diagnosed with CSP, 30 received local MTX injection. The initial serum ß- human chorionic gonadotropin (hCG) level in the failure group was significantly higher than in the success group (p = 0.048), and the cut-off value was 47,000 mIU/ml. The rate of type 2 position of the gestational sac in the failure group was significantly higher than in the treatment success group (p = 0.031). A high initial serum ß-hCG level (≥ 47,000 mIU/ml) was identified as the independent risk factor for treatment failure (adjusted odds ratio = 21.9; 95% confidence interval = 1.3-383.1). Type 2 gestational sac position and a higher level of ß-hCG at diagnosis appear to be associated with poor outcomes after local injection of a single dose of MTX., Competing Interests: The authors have no conflicts of interest to declare.

Objectives: To determine the role of baseline ultrasound findings and the changes between β- human chorionic gonadotropin (hCG) values on day 0 to day 4 in patients receiving single-dose methotrexate (MTX) therapy for tubal ectopic pregnancy., Material and Methods: One hundred fourteen patients who were hospitalized with a diagnosis of ectopic pregnancy and treated with single-dose methotrexate were included in this retrospective study. The successful treatment group (n = 88) comprised patients in whom serum β-hCG levels were resolved with single-dose methotrexate treatment, and the failed treatment group (n = 26) included patients who received second dose methotrexate and/or surgery. Ultrasound findings, laboratory findings, and serum β-hCG values at the time of admission and D4 and D7 β-hCG values were compared., Results: The success rate of single-dose methotrexate treatment was 77.2%. In the successful treatment group, the initial β-hCG values of the patients were lower than the unsuccessful treatment group (1479.14 ± 1253.49, 4442.88 ± 3392.58, respectively) (p = 0.0001). A decrease of more than 35% between D0-D4 increased the probability of successful treatment (p = 0.017). Although ectopic focus size and abdominal free fluid showed no significant difference between the two groups, endometrial stripe thickness was significantly higher in the unsuccessful treatment group (12.61 ± 5.79, 9.28 ± 3.53) (p = 0.002)., Conclusions: In addition to the basal β-hCG value, endometrial stripe thickness of ultrasound findings should also be considered in determining patients with a high chance of success in single-dose MTX treatment.β-hCG changes between D0-D4 may be advantageous in the clinical management of ectopic pregnancy for earlier evaluation.

Objective: The M6 risk-prediction model was published as part of a two-step protocol using an initial progesterone level of ≤ 2 nmol/L to identify probable failing pregnancies (Step 1) followed by the M6 model (Step 2). The M6 model has been shown to have good triage performance for stratifying women with a pregnancy of unknown location (PUL) as being at low or high risk of harboring an ectopic pregnancy (EP). This study validated the triage performance of the two-step protocol in clinical practice by evaluating the number of protocol-related adverse events and how effectively patients were triaged., Methods: This was a prospective multicenter interventional study of 3272 women with a PUL, carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the UK. The final pregnancy outcome was defined as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an EP (including persistent PUL (PPUL)). FPUL and IUP were grouped as low-risk and EP/PPUL as high-risk PUL. Serum progesterone and human chorionic gonadotropin (hCG) levels were measured at presentation in all patients. If the initial progesterone level was ≤ 2 nmol/L, patients were discharged and were asked to have a follow-up urine pregnancy test in 2 weeks to confirm a negative result. If the progesterone level was > 2 nmol/L or a measurement had not been taken, hCG level was measured again at 48 h and results were entered into the M6 model. Patients were managed according to the outcome predicted by the protocol. Those classified as 'low risk, probable FPUL' were advised to perform a urine pregnancy test in 2 weeks and those classified as 'low risk, probable IUP' were invited for a scan a week later. When a woman with a PUL was classified as high risk (i.e. risk of EP ≥ 5%) she was reviewed clinically within 48 h. One center used a progesterone cut-off of ≤ 10 nmol/L and its data were analyzed separately. If the recommended management protocol was not adhered to, this was recorded as a protocol deviation and classified as: unscheduled visit for clinician reason, unscheduled visit for patient reason or incorrect timing of blood test or ultrasound scan. The classifications outlined in the UK Good Clinical Practice (GCP) guidelines were used to evaluate the incidence of adverse events. Data were analyzed using descriptive statistics., Results: Of the 3272 women with a PUL, 2625 were included in the final analysis (317 met the exclusion criteria or were lost to follow-up, while 330 were evaluated using a progesterone cut-off of ≤ 10 nmol/L). Initial progesterone results were available for 2392 (91.1%) patients. In Step 1, 407 (15.5%) patients were classified as low risk (progesterone ≤ 2 nmol/L), of whom seven (1.7%) were ultimately diagnosed with an EP. In 279 of the remaining 2218 women with a PUL, the M6 model was not applied owing to protocol deviation or because the outcome was already known (usually on the basis of an ultrasound scan) before a second hCG reading was taken; of these patients, 30 were diagnosed with an EP. In Step 2, 1038 women with a PUL were classified as low risk, of whom eight (0.8%) had a final outcome of EP. Of 901 women classified as high risk at Step 2, 275 (30.5%) had an EP. Therefore, 275/320 (85.9%) EPs were correctly classified as high risk. Overall, 1445/2625 PUL (55.0%) were classified as low risk, of which 15 (1.0%) were EP. None of these cases resulted in a ruptured EP or significant clinical harm. Sixty-two women participating in the study had an adverse event, but no woman had a serious adverse event as defined in the UK GCP guidelines., Conclusions: This study has shown that the two-step protocol incorporating the M6 model effectively triaged the majority of women with a PUL as being at low risk of an EP, minimizing the follow-up required for these patients after just two visits. There were few misclassified EPs and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two-step protocol incorporating the M6 model is an effective and clinically safe way of rationalizing the management of women with a PUL. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Methotrexate (MTX) is the prior drug in ectopic pregnancy (EP). However, approximately 10% of patients suffer from failure by MTX therapy. Reduced folate carrier 1 (RFC1), methylene tetrahydrofolate reductase (MTHFR), and dihydrofolate reductase (DHFR) are involved in the transport and effects of MTX in vivo. In the present study, we aim to investigate the relationship between the genetic polymorphisms of RFC1, MTHFR, and DHFR and the clinical efficacy of MTX in tubal pregnancies., Methods: 100 patients of EP were enrolled in this study. Polymorphisms of RFC1 G80A, MTHFR C677T, and DHFR A-317G were genotyped. β-hCG level was detected in day 0, 4, and 7 after MTX injection. Association of MTX efficacy and genetic polymorphisms was analyzed., Results: Methylene tetrahydrofolate reductase C677T was associated with MTX treatment (P = .017). The success rate of first MTX injection was superior in patients with harboring mutation allele of MTHFR gene than that in patients with wild-type gene (P = .001). However, there was no significant association between the polymorphisms of RFC1 G80A, DHFR A-317G, and surgical treatment (P = .709 and .476, respectively). In addition, β-hCG level decrement was not significantly changed by MTX injection with different polymorphisms of RFC1, MTHFR, and DHFR on either day 4 (P = .214, 0.197 and 0.270, respectively) or day 7 (P = .172, .554, and .726, respectively)., Conclusion: Our results suggested that the reliable indicator was polymorphism of MTHFR C677T in failure by MTX injection., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Background: The diagnosis of ectopic pregnancy (EP) is challenging and 40-50% of patients are initially misdiagnosed., Methods: This prospective case-control study measured activin-A, activin-B, activin-AB and follistatin for the diagnosis of EP, spontaneous abortion (SAB) and normal intrauterine pregnancy (IUP). Sera were collected from 120 women with symptoms suggesting early pregnancy failure and who were clinically diagnosed as IUP, SAB or EP (n = 40/group). The markers were measured by ELISA and their area under the curve (AUC), cut-off value, sensitivity and specificity were determined by receiver-operating characteristic curve. The results were compared with serum β-human chorionic gonadotropin and progesterone., Results: Activin-A and activin-B decreased significantly, while activin-AB and follistatin increased, in the EP and SAB groups than the IUP group. Activin-AB (AUC = 0.961) and progesterone (AUC = 0.973) were the best markers for EP and SAB, respectively. Activin-AB (≥61.5 pg/mL) showed 92.5% sensitivity, 85% specificity, 75.5% positive predictive value (PPV) and 95.8% negative predictive value (NPV) for EP. Progesterone (≤6.3 ng/mL) had 100% sensitivity, 86.2% specificity, 78.4% PPV and 100% NPV for SAB., Conclusions: Serum activins and follistatin were significantly altered with EP and activin-AB could be a promising marker for the diagnosis of EP., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ectopic pregnancy occurs when a fertilized ovum attaches outside the uterus. As a complication in approximately 1‑2% of all pregnancies, ectopic pregnancies may cause catastrophic hemorrhage as a result of invading maternal blood vessels. Therefore, early diagnosis and timely treatment are crucial for women with ectopic pregnancy. In this study, we aimed to identify and determine the efficacy of serum biomarkers for the prompt diagnosis of ectopic pregnancy. For this purpose, the serum concentrations of progesterone, β human chorionic gonadotropin (β‑hCG) and cancer antigen‑125 (CA125) were detected by solid‑phase, competitive binding chemiluminescent enzyme immunoassays. Flow cytometry was used to analyze the percentage of CD3+ T cells in women with ectopic pregnancy. Pathological analysis of tubal and villus tissues was performed by hematoxylin and eosin (H&E) staining. After receiving an injection of methotrexate (MTX), patients were examined by transvaginal ultrasound to detect the size of the echogenic mass. The results revealed that the serum levels of progesterone, β‑HCG and CA125 were significantly decreased in women with ectopic pregnancy, whereas the percentage of CD3+ T cells was increased in women with ectopic pregnancy. Histopathological examination revealed blood clots with small tissue fragments of a tubal‑type epithelium and incomplete pile structures. Five days after the MTX injection, an echogenic mass was found with a size of 1.7x1.2x1.6 cm that contained a gestational sac‑like structure and a yolk sac. On the whole, the findings of this study indicate the at the joint detection of progesterone, β‑HCG, CA125 serum levels and the CD3+ T cell percentage could be applied as a reliable indicator for the early diagnosis of ectopic pregnancy. MTX administration was determined to be an efficacious approach for the treatment of ectopic pregnancy.

We investigated various monitoring protocols on the success of methotrexate therapy in patients with tubal ectopic pregnancy. The data from patients who received single-dose methotrexate therapy as their first-line treatment was reviewed. The Beta-human chorionic gonadotropin (BhCG) days 1-4 and days 1-7 follow-up protocols were compared with the BhCG day 4-7 follow-up protocol, in terms of the treatment. Cut-off values were determined for the reduction of BhCG between the days 1-4 and days 1-7. There were no significant differences between the groups in terms of the demographic data, except for BhCG fourth- and seventh-day values. There was a 21% decrease in BhCG between days 1 and 4 and a 32% decrease for BhCG between days 1 and 7 as good predictors for treatment success. These follow-up protocols allow earlier and more cost-effective methods than the protocol based on a 15% reduction in BhCG levels between days 4 and 7. Impact statement What is already known on this subject? A decrease of 15% BhCG levels between days 4 and 7 is a common protocol for predicting the success of a single-dose methotrexate therapy of an ectopic pregnancy. What do the results of this study add? This clinical study offers the cut-off values for the various BhCG follow-up protocols recently found in the literature for single-dose methotrexate therapy for the treatment of ectopic pregnancy. What are the implications of these findings for clinical practice and/or further research? We identified the importance of fourth-day BhCG for measuring the success of single-dose methotrexate therapy. Therefore, after randomised, multicentre, prospective clinical trials, the most common follow-up protocol can be changed to a single-dose methotrexate therapy for ectopic pregnancy.

Research Question: Several studies have tried to identify early markers of treatment outcome after methotrexate (MTX) treatment for ectopic pregnancy, including pretreatment and day 4 human chorionic gonadotrophin (HCG) concentrations and their corresponding changes, and the increment in HCG during the initial 24 h after treatment. There have, however, been conflicting results. This study aimed to re-evaluate the role of these markers in the earlier identification of treatment success in a large cohort of women., Design: This was a retrospective cohort study including women diagnosed with an ectopic pregnancy and treated with a regimen of a single dose of MTX. A comparison of maternal and gestation characteristics was made between groups in whom treatment was successful or failed., Results: A total of 292 women treated with single-dose intramuscular MTX for ectopic pregnancy were included in this study. In the overall cohort, the treatment success rate with a single dose of MTX was 62.7% (183/292). Only two independent determinants were significantly associated with treatment success: the initial 24-h percentage increase in HCG (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] 1.26-2.63; P < 0.001) and the percentage change in HCG from day 1 to day 4 (adjusted OR 1.12, 95% CI 1.04-1.21; P < 0.001). The optimal cut-off points for prediction of treatment success were an increment of less than 17% in the 24 h before treatment and a decrease of more than 22% between the day 1 and day 4 HCG concentrations., Conclusions: A small increase in HCG concentration 24 h before treatment with MTX, alongside a decline in HCG concentration from day 1 to day 4, may predict the success of medical treatment for an ectopic pregnancy., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Ectopic pregnancies constitute about 2% of all pregnancies which are the leading cause of pregnancy-related deaths and a considerable cause of maternal morbidity. Oxidative stress can lead to a number of pregnancy related diseases including miscarriage, eclampsia and preterm labor. Ischemia modified albumin (IMA) which reflects the oxidative stress may be used as a marker for ectopic pregnancy. Our aim was to compare the levels of IMA and total antioxidant status (TAS) in ectopic and normal pregnancies and to understand if IMA can be used as a marker to diagnose ectopic pregnancy., Materials and Methods: Our case-control study consisted of 38 women with ectopic and 42 women with normal pregnancy. IMA and TAS levels were determined in serum samples with an albumin-cobalt binding test and by commercially available kits, respectively. IMA levels were adjusted according to serum albumin levels. Index of oxidation (IOS) was calculated by dividing adjusted IMA (A-IMA) levels with TAS. A receiver operating characteristics (ROC) curve analysis was made and cut-off values for the biomarkers were investigated in SPSS 21.0 program (SPSS, Chicago, IL). Data were presented as mean ± standard deviation and a p value < .05 was accepted as statistically significant., Results: There was a statistically significant difference in IMA, A-IMA, and IOS levels between ectopic and normal pregnancies. Although TAS level was not different statistically, it was lower in ectopic pregnancy. According to ROC curve analysis, IOS had the largest area under curve. A cut-off value of 0.545 for IOS had 81.6% sensitivity and 59.5% specificity., Conclusions: According to our study, oxidative stress plays an important role in ectopic pregnancy and either A-IMA or IOS can be evaluated as a marker of ectopic pregnancy after further studies.

Objective: To report clinical experience with methotrexate (MTX) treatment for suspected but not definite ectopic pregnancy (EP)., Methods: This was a retrospective cohort study. All patients treated with MTX for presumed EP between 2000 and 2016 were included. Demographic, clinical, sonographic, and outcome data were collected and analyzed., Results: A total of 820 patients were treated with MTX, 692 (84.4%) of which were lacking definitive features of EP; 155 (22.4%) failed to follow up until complete resolution and were excluded. Retrospective sonographic categorization was applied to 537 patients; of those patients, 393 (73.2%) were categorized as probable EPs, 136 (25.3%) pregnancies of unknown location (PULs), and 8 (1.5%) probable intrauterine pregnancies (IUPs). Sixteen were eventually diagnosed with IUP: 6 from the probable EPs, 9 from the PULs, and 1 from the probable IUP group. Patients with final diagnosis of IUP had higher values of β-human chorionic gonadotropin as well as lower prevalence of adnexal mass (38% versus 74%; P = .003), higher prevalence of intracavitary fluid (44% versus 9%; P = .0004) and thicker endometrium (17.1 ± 11.8 versus 9.7 ± 5.6; P = .04). None of the sonographic parameters were able to distinguish patients with IUP. One patient of the 16 with IUP was diagnosed with a viable pregnancy, and 7 additional patients had a possible viable pregnancy. None of them elected to continue the pregnancy., Conclusions: Most patients with suspected EP who are eligible for medical treatment lack definitive sonographic features of EP. Treatment with MTX in such cases should be delayed, as clinically reasonable, to improve the diagnosis and prevent inadvertent administration of MTX to patients with a viable IUP., (© 2018 by the American Institute of Ultrasound in Medicine.)

Early diagnosis of an extrauterine pregnancy is important for safe and effective management. However, a pregnancy's location often cannot be easily determined with abnormal implantations or prior to 5-6 weeks' gestation. Multiple testing strategies exist to diagnose an abnormal pregnancy when location is unknown, but caution needs to be used to avoid a false diagnosis. Medical treatment is optimal when an abnormal pregnancy is diagnosed early. Because most of these pregnancies are intrauterine, additional testing to localize the pregnancy will allow the correct choice of therapy and avoids unnecessary exposure to a toxic therapy. This testing strategy should be reserved for patients with significant concern for ectopic pregnancy, based on either risk factors or clinical findings. Overuse of this approach can lead to interruption of normal pregnancies., (Copyright © 2018. Published by Elsevier Inc.)

Background: There is no international consensus on how to manage women with a pregnancy of unknown location (PUL)., Objectives: To present a systematic quantitative review summarising the evidence related to management protocols for PUL., Search Strategy: MEDLINE, COCHRANE and DARE databases were searched from 1 January 1984 to 31 January 2017. The primary outcome was accurate risk prediction of women initially diagnosed with a PUL having an ectopic pregnancy (high risk) as opposed to either a failed PUL or intrauterine pregnancy (low risk)., Selection Criteria: All studies written in the English language, which were not case reports or series that assessed women classified as having a PUL at initial ultrasound., Data Collection and Analysis: Forty-three studies were included. QUADAS-2 criteria were used to assess the risk of bias. We used a novel, linear mixed-effects model and constructed summary receiver operating characteristic curves for the thresholds of interest., Main Results: There was a high risk of differential verification bias in most studies. Meta-analyses of accuracy were performed on (i) single human chorionic gonadotrophin (hCG) cut-off levels, (ii) hCG ratio (hCG at 48 hours/initial hCG), (iii) single progesterone cut-off levels and (iv) the 'M4 model' (a logistic regression model based on the initial hCG and hCG ratio). For predicting an ectopic pregnancy, the areas under the curves (95% CI) for these four management protocols were as follows: (i) 0.42 (0.00-0.99), (ii) 0.69 (0.57-0.78), (iii) 0.69 (0.54-0.81) and (iv) 0.87 (0.83-0.91), respectively., Conclusions: The M4 model was the best available method for predicting a final outcome of ectopic pregnancy. Developing and validating risk prediction models may optimise the management of PUL., Tweetable Abstract: Pregnancy of unknown location meta-analysis: M4 model has best test performance to predict ectopic pregnancy., (© 2018 Royal College of Obstetricians and Gynaecologists.)

This retrospective cohort study investigates the risk factors and beta-human chorionic gonadotropin (β-hCG) trends in patients with ruptured tubal ectopic pregnancies (EPs) despite methotrexate (MTX) treatment. All patients receiving MTX for sonographically confirmed tubal EPs at our fertility center between 2004 and 2014 were included. Baseline demographics and β-hCG trends of patients with EP rupture after MTX were compared to patients with resolved EPs after MTX. One-hundred-thirty-seven patients with EPs were treated with MTX during the study duration; 27 experienced EP rupture and 110 EP resolution. There was no difference in the baseline demographics or β-hCG levels on the day of MTX between the groups. Patients with ruptured EPs after MTX had higher β-hCG levels on day-4 (1223.9 ± 243.5 vs. 1111.2 ± 179.7 mIU/mL; p < .001) and day-7 (1156.9 ± 206.2 vs. 872.4 ± 690.2 mIU/mL; p < .001). The odds of EP rupture compared to EP resolution was 6.2 (95% CI 2.1-19.1), 13.7 (95% CI 4.8-38.9), and 3.0 (95% CI 1.2-7.2) times higher when the change in β-hCG levels was <5% between day-7 vs. day of MTX, day-7 vs. day-4, and day-4 vs. day of MTX, respectively. Our results demonstrate that ruptured tubal EPs despite MTX have <5% change in β-hCG levels between the day of MTX and day-4 or day-7 after MTX.

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., (© 2018 by the American Institute of Ultrasound in Medicine.)

Objective: To determine the association between early increase in the serum hCG levels (days 0-4) and treatment success rates following methotrexate therapy in ectopic pregnancy patients., Study Design: A level II-2 case-control study of involving 140 patients treated with methotrexate for ectopic pregnancy at the gynecology department in a tertiary care hospital., Results: A logistic regression model for the "failure of treatment" was fitted with serum hCG levels change between day 0 and day 4, patient age, pregnancy age at day-0, and day-0 β-hCG level as predictors. The logistic regression analysis indicated that having more than 50% increase in the β-hCG levels between days 0 and 4 significantly (P = 0.011) increases the risk of MTX treatment failure., Conclusion: The results of this study indicate that >50% increase in β-hCG levels between days 0 and 4 significantly increases the risk of methotrexate treatment failure. This novel information could assist patients and physicians in making decisions regarding ectopic pregnancy treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Research Question: Does salpingectomy for ectopic pregnancy affect the ovarian reserve measured by changes in pre- and post-operative levels of anti-Müllerian hormone (AMH)?, Design: This is a prospective observational multicentre study of 64 women treated with salpingectomy for an ectopic pregnancy. AMH was measured in serum samples collected at admission before salpingectomy and at follow-up (median time to follow-up [interquartile range] was 3 [3-4] months). Changes in serum AMH levels were investigated using Wilcoxon signed-rank test and the relationship between changes in AMH and age, time to follow-up, and pre-operative serum AMH level was investigated using linear regression analysis. The biological variation of AMH was also calculated., Results: Serum AMH levels did not differ significantly before and after salpingectomy (median ∆AMH [follow-up value minus admission value] 0.40 pmol/l, interquartile range -2.0 to 4.0 pmol/l). ΔAMH was independent of age, time to follow-up and pre-operative serum AMH level. The intra-individual biological variation for AMH ranged from 12.1% to 26.3%, depending on time between the two samples., Conclusions: This is the first paired study to investigate serum AMH values before and after salpingectomy in an unselected population of women presenting with an ectopic pregnancy, including both patients who conceived naturally and following fertility treatment. It was found that salpingectomy for ectopic pregnancy had no short-term effect on serum AMH levels, and changes in AMH levels were independent of age, time to follow-up, and pre-operative serum AMH level. Furthermore, the study demonstrated a 6-month biological variation of AMH of less than 30%., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: Pregnancy of unknown location (PUL) is not a diagnosis but a transient state used to classify a woman when she has a positive pregnancy test without definitive evidence of an intra-uterine or extra-uterine pregnancy on transvaginal ultrasonography. Management of a persisting PUL varies substantially, including expectant or active management. Active management can include uterine cavity evacuation or systemic administration of methotrexate. To date, no consensus has been reached on whether either management strategy is superior or non-inferior to the other., Design: Randomized controlled trial., Setting: Academic medical centers., Patients: We plan to randomize 276 persisting PUL-diagnosed women who are 18 years or older from Reproductive Medicine Network clinics and additional interested sites, all patients will be followed for 2 years for fertility and patient satisfaction outcomes., Interventions: Randomization will be 1:1:1 ratio between expectant management, uterine evacuation and empiric use of methotrexate. After randomization to initial management plan, all patients will be followed by their clinicians until resolution of the PUL. The clinician will determine whether there is a change in management, based on clinical symptoms, and/or serial human chorionic gonadotropin (hCG) concentrations and/or additional ultrasonography., Main Outcome: The primary outcome measure in each of the 3 treatment arms is the uneventful clinical resolution of a persistent PUL without change from the initial management strategy. Secondary outcome measures include: number of ruptured ectopic pregnancies, number and type of re-interventions (additional methotrexate injections or surgical procedures), treatment complications, adverse events, number of visits, time to resolution, patient satisfaction, and future fertility., Conclusion: This multicenter randomized controlled trial will provide guidance for evidence-based management for women who have persisting pregnancy of unknown location., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The purpose of this study is to investigate the relationship between the blood level of cadmium and the occurrence of ectopic pregnancy. Forty-one (41) case patients with ectopic pregnancy and 41 uncomplicated intrauterine pregnant patients as controls were recruited. The concentrations of cadmium (Cd) were measured from blood samples using atomic absorption spectrometry. The cases and controls were similar in age, body mass index, and smoking habits. The median blood level of Cd was 0.32 μg/l (interquartile range [IQR] 0.00-0.71) in the women with ectopic pregnancies and 0.34 μg/l (IQR 0.09-0.59) in the controls. There was no significant association between blood cadmium levels and ectopic pregnancy.