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Objective: To investigate the systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) in predicting a successful methotrexate response in tubal ectopic pregnancy (TEP)., Methods: Women treated for TEP at a tertiary hospital between 2017 and 2021 were retrospectively reviewed. A total of 502 (100%) eligible patients who received methotrexate were included and divided into two groups based on whether or not they were successfully treated with methotrexate alone. Inflammatory parameters derived from the patients' hemograms at hospital admission were compared., Results: In total, 434 (86.4%) patients were successfully treated with methotrexate alone (Group 1), while 68 (13.6%) patients underwent surgery after methotrexate failure (Group 2). Median neutrophil count, NLR, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, SII, largest ectopic mass diameter, and β-human chorionic gonadotropin (β-hCG) were significantly lower, whereas median lymphocyte and platelet counts were significantly higher in Group 1. According to the receiver operating characteristic analysis performed for the discriminatory power of NLR, β-hCG, and SII for methotrexate response, the area under the curve values were 0.742, 0.730, and 0.699, respectively., Conclusion: Low NLR and SII are associated with methotrexate success and could be used to refine decision making regarding β-hCG for predicting successful response to methotrexate in patients with TEP., (© 2024 International Federation of Gynecology and Obstetrics.)

Objective: To identify risk factors for readmission following methotrexate treatment for tubal pregnancy., Methods: A retrospective study undertaken in two tertiary medical centers, including all individuals with medically treated tubal pregnancy (N = 511), between December 2009 and June 2021. Individuals with and without readmission following methotrexate treatment were compared. The primary outcome was the readmission rate. Secondary outcomes included the rate of post-discharge gynecological emergency department visits, tubal rupture rate, and the eventual need for surgical treatment., Results: Readmission following methotrexate treatment occurred in 224/511 patients (43.8%). Most readmissions were due to abdominal pain or suspicion of treatment failure. Readmitted individuals were more likely to have a history of pelvic inflammatory disease and pretreatment serum human chorionic gonadotropin (hCG) >2000 mIU/mL. Both factors remained significantly associated with higher readmission rates in a logistic regression analysis (adjusted odds ratio [OR] 6.28, 95% confidence interval [CI] 1.30-30.45, and adjusted OR 2.73, 95% CI 1.83-4.07, respectively) after adjustment for age, endometriosis, tubal pathology, abdominal pain, and presence of yolk sac or embryo at diagnosis. A dose-dependent association was observed between pretreatment serum hCG levels and readmission rate (P < 0.001). Pretreatment hCG levels were also associated with tubal rupture and the eventual need for surgical treatment (P < 0.001 for both). A prediction model using hCG was not sufficiently accurate to predict readmission risk., Conclusion: Readmission following methotrexate treatment for tubal pregnancy was independently associated with previous pelvic inflammatory disease and pretreatment serum hCG levels. The latter was also associated with surgical intervention rate., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy remain controversial. This study investigated the outcomes of ectopic pregnancy after one and two MTX doses and their independent predictors., Methods: Retrospective cross-sectional study of women who consented to MTX treatment in 2017-2018 at our institution ( N  = 317). Of these, patients with Caesarean scar pregnancies were excluded because they require different treatment protocols ( n  = 25). All patients were treated according to our institution's protocol based on international guidelines and standardised across the three hospitals included in the current study. We retrieved patients' demographics, laboratory, ultrasonography, and clinical characteristics from our hospital database. Serum β-human chorionic gonadotropin (β-hCG) was measured using electrochemiluminescence immunoassay; ectopic pregnancy was diagnosed using ultrasonography (transvaginal probe)., Results: Two ninety-two patients were included in the current analysis. Age, pre-treatment β-hCG levels, sonographic presence of yolk sac, presence of foetal cardiac activity, and pelvic pain were significantly different between patients with successful and unsuccessful outcomes. Younger age (adjusted odds ratio [aOR] 2.33, 95% confidence interval (CI) 1.16-4.66, p  = .017), no pelvic pain (aOR 2.65, 95%CI 1.03-6.83, p  = .043), lower initial β-hCG level (aOR 1.32, 95%CI 1.08-1.59, p  = .005), and absence of foetal cardiac activity (aOR 12.63; 95% CI 1.04-153.6; p  = .047) were independently associated with success. Treatment failure odds were >2 folds higher for each 10-year age increase ( p  = .017), 32% higher for each 1000 IU/L increase in initial β-hCG level ( p  = .005), and >2 folds higher in presence of pelvic pain ( p  = .043)., Conclusions: MTX is effective in most patients, averting invasive surgery, which might affect fertility. Pre-treatment β-hCG levels, age, pelvic pain, and foetal cardiac activity was independently associated with outcomes. Research should assess the relationship between the ectopic pregnancy size and treatment outcomes and refine β-hCG titres where treatment would be ineffective.

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: Chronic ectopic pregnancy is a variant of ectopic pregnancy featured with a low or normal serum beta-human chorionic gonadotropin (β-hCG) test. Obscure clinical presentations and non-specific images make chronic ectopic pregnancy a diagnostic dilemma until now., Case Report: A 40-year-old female was misdiagnosed as tubo-ovarian abscess initially due to chronic lower abdominal pain, negative pregnancy test, and a complicated pelvic mass on abdominal CT scan and serial follow-up ultrasonography. Diagnostic laparoscopy was performed because of persistent pelvic mass with abdominal pain and irregular vaginal bleeding. Left tubal salpingectomy was performed and pathology reported a hematocele with inactive trophoblast tissue. Chronic ectopic pregnancy was proved. The symptoms resolved completely after our surgery., Conclusion: An abnormal adnexal mass with a history of recent pregnancy could still be possible for chronic ectopic pregnancy even with a negative pregnancy test. Diagnostic laparoscopy and pathology confirmation could be helpful when the clinical manifestation is confusing., (Copyright © 2024. Published by Elsevier B.V.)

We herein report a rare case of simultaneous intrauterine molar pregnancy and tubal pregnancy. A woman of childbearing age who had never been pregnant underwent an ultrasound examination 70 days after the onset of menopause. She had a history of ovulation induction. The ultrasound findings suggested a partial hydatidiform mole. She was then pathologically confirmed to have a complete hydatidiform mole after uterine suction dilation and curettage. On postoperative day 4, an ultrasound examination before discharge showed an inhomogeneous mass in the left adnexal region with mild lower abdominal pain. On postoperative day 17, the blood human chorionic gonadotropin level did not drop as expected, and a follow-up examination still indicated a mass in the left adnexal region. We were unable to rule out an ectopic hydatidiform mole. Hysteroscopy with laparoscopic exploration of the left adnexal mass and salpingotomy suggested a diagnosis of intrauterine hydatidiform mole combined with left tubal pregnancy., Competing Interests: Declaration of conflicting interestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: The single-dose methotrexate (MTX) regimen is effective and minimizes side effects but an additional second dose is needed in case of failure in an ectopic pregnancy (EP). We aimed to predict the additional MTX dose by evaluating the change in β-hCG values between day 0 and day 4 in EPs with administered single-dose MTX regimen., Method: A total of 454 tubal EPs between 2013 and 2019 were evaluated retrospectively. Cases cured with a single dose of MTX without an additional dose were accepted as the control group, and cases under a single-dose regimen were cured by applying a second dose of MTX on the 7th day were accepted as the study group. Obstetric and demographic characteristics and the change in β-hCG values compared in both groups., Results: Age, body mass index (BMI), gravida, smoking, abdominal surgery, presence of IUDs, initial β-hCG levels (0th day), and EP size were similar in both groups, but the presence of previous EP history was significantly higher in the study group. The change of β-hCG from days 0 and 4 determined that a 20% increase predicts the need for a second dose of MTX with 72.4% sensitivity, and 87.8% negative predictive value (NPV)., Conclusion: The single-dose MTX protocol is successful in 83.3% of convenient cases (as the control group), but an increase of 20% in β-hCG between days 0 and 4 predicts the patients who need to be administered second-dose MTX, and thus, a double-dose MTX protocol will be achieved early., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: We aimed to assess the impact of the coronavirus disease 2019 pandemic on the clinical presentation of tubal ectopic pregnancies., Methods: This retrospective cohort study was conducted at a tertiary center and included 76 cases of tubal ectopic pregnancies. The study period was divided into two groups: the pre-coronavirus disease group (January 2018 to February 2020, Group 1; n=47, 61.8%) and the coronavirus disease group (March 2020 to February 2022, Group 2; n=29, 38.2%). Subgroup analysis was also performed for tubal ruptured ectopic pregnancies as Group 1 (n=15, 62.5%) and Group 2 (n=9, 37.5%)., Results: No statistically significant differences were observed between the pre-coronavirus disease and coronavirus disease groups in terms of demographic characteristics. Although the serum beta-human chorionic gonadotropin level was found to be higher in Group 2, the difference was not statistically significant (p=0.7). The groups appeared to be similar in treatment management, duration of hospitalization, and blood transfusion needs (p=0.3, p=0.6, and p=0.5, respectively). Additionally, no significant difference was observed between the groups in the evaluation of ruptured ectopic pregnancies (p=0.5). In the subgroup analysis of tubal ruptured ectopic pregnancies, no significant difference was observed., Conclusion: To the best of our knowledge, there are few studies evaluating the effect of the pandemic on tubal ectopic pregnancies in the literature. Although we did not report statistically significant differences between groups in our study, given the potential prolonged duration of the pandemic, healthcare professionals should actively prompt their patients to seek necessary medical assistance.

Objective: The objective of this study was to evaluate whether a single measurement of vascular endothelial growth factor could distinguish between intrauterine pregnancy and ectopic pregnancy and to correlate the levels of vascular endothelial growth factor with serum levels of progesterone andβ-human chorionic gonadotropin in each subgroup., Methods: Ninety patients with a positive human chorionic gonadotropin test and either abdominal pain or vaginal bleeding were selected; pregnancies were singletons, spontaneously conceived, 42-56 days of gestational age. All patients had a transvaginal ultrasound examination and were divided into three subgroups: abnormal intrauterine pregnancy, tubal pregnancy, and normal intrauterine pregnancy. Tubal pregnancies were surgically treated and histologically confirmed. Blood samples were collected for the determination of β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor and their concentrations were compared in each subgroup. Receiver operating characteristic curve was calculated by comparing the subgroup of tubal pregnancy to the other groups. A Fisher discriminant function analysis was performed. The level of significance was 5%., Results: One-way analysis of variance revealed a significant correlation between the different subgroups and β-human chorionic gonadotropin, progesterone, and vascular endothelial growth factor serum levels (p<0.001). Vascular endothelial growth factor concentration was significantly higher for patients with tubal pregnancy than for other subgroups (p<0.05). β-Human chorionic gonadotropin and progesterone levels were higher in the subgroup with normal intrauterine pregnancies compared with the subgroups with tubal and abnormal intrauterine pregnancies (p<0.05). Serum vascular endothelial growth factor level >188.7 ng/mL predicted tubal pregnancy with 96.7% sensitivity, 95.0% specificity, 90.6% positive predictive value, and 98.3% negative predictive value., Conclusions: Serum vascular endothelial growth factor could be a marker in discriminating intrauterine pregnancy from tubal pregnancy; its levels are increased in women with ectopic pregnancy compared with women with normal and abnormal intrauterine pregnancies.

Objective: To evaluate serum protein calponin 2 (CNN2) as a candidate biomarker for tubal ectopic pregnancy (EP)., Design: Retrospective study., Setting: Single University affiliated tertiary hospital., Patient(s): Serum samples were obtained from 84 patients with EP, 39 with viable intrauterine pregnancy (vIUP), and 42 with miscarriage. Moreover, 10 fallopian tube and corresponding villous tissue samples from patients with EP, 6 villous tissue samples from patients with vIUP, and 10 villous tissue samples from patients with miscarriage were collected., Intervention(s): Serum CNN2 concentrations were measured using enzyme-linked immunosorbent assay; CNN2 expression in tissues was evaluated via immunohistochemistry and quantitative real-time polymerase chain reaction analysis., Main Outcome Measure(s): The diagnostic performance of serum CNN2 to discriminate an EP from vIUP and miscarriage., Result(s): CNN2 was highly expressed in villous stromal cells isolated from patients with EP, and CNN2 messenger ribonucleic acid expression was upregulated in villous tissues from women with EP compared with that in women with vIUPs and miscarriages. Serum CNN2 concentration was higher in women with EP than that in women with vIUP and miscarriage. The serum CNN2 predicted EP from vIUP and miscarriage with areas under the curve (AUCs) of 0.931 (95% confidence interval: 0.889-0.975). For discriminating EP from miscarriage only, the AUC was 0.906 (95% confidence interval: 0.835-0.977). In contrast, the AUCs for serum human chorionic gonadotropin were 0.809 and 0.637, respectively., Conclusion(s): Our data highlight the possibility of serum CNN2 as a single biomarker for the diagnosis of EP., Clinical Trial Registration Number: ChiCTR 1900020483., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier 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.

We present a case of a tubal ectopic pregnancy (EP) in a patient with an initially undetectable serum β-human chorionic gonadotropin (β-hCG) level. A 33-year-old woman in a same-sex relationship underwent timed donor intrauterine insemination. Her serum β-hCG level was <5 mIU/mL 14 days after the intrauterine insemination. She reported menstrual bleeding 3 days after her negative pregnancy test and returned to the office 10 days later to begin a new treatment cycle. Her serum levels of estradiol, progesterone, and β-hCG were 119 pg/mL, 6.1 ng/mL and 1157 mIU/mL, respectively. Transvaginal ultrasonography did not show an intrauterine pregnancy. Her β-hCG level increased to 1420 mIU/mL the next day. She was diagnosed with a pregnancy of unknown location and treated with methotrexate. Her β-hCG levels continued to increase despite 3 methotrexate doses, necessitating laparoscopy. The diagnostic laparoscopy demonstrated approximately 100 mL of hemoperitoneum in the posterior cul-de-sac with an intact right fallopian tube that was dilated at its distal end by the EP. A total right salpingectomy was performed. Her β-hCG level was <5 mIU/mL 3 weeks later. The current case supports that although rare, an undetectable serum β-hCG level does not completely rule out the diagnosis of an EP., (Copyright © 2020 AAGL. Published by Elsevier Inc. All rights reserved.)

Research Question: What is the time required for complete physical resolution of tubal ectopic pregnancies diagnosed on ultrasound imaging in women undergoing successful expectant management?, Design: A prospective observational cohort study of 177 women who had successful expectant management of tubal ectopic pregnancy, who attended a single Early Pregnancy Unit between January 2014 and December 2018. All participants were monitored until their serum beta-human chorionic gonadotrophin (beta-HCG) dropped to non-pregnant concentrations and with 2-weekly follow-up ultrasound scans until resolution of the pregnancy., Results: A total of 112/177 (63.3%, 95% confidence interval [CI] 55.7-70.4) of tubal ectopic pregnancies were indiscernible on ultrasound 2 weeks after serum beta-HCG had returned to non-pregnant concentrations. In 8/177 (4.5%, 95% CI 2.0-8.7), physical resolution took longer than 78 days. There was a positive correlation between biochemical and physical resolution of tubal ectopic pregnancy (r = 0.21, P = 0.006)., Conclusions: Physical resolution of tubal ectopic pregnancy is often prolonged and is positively correlated with initial and maximum beta-HCG concentrations. Results of this study indicate that beta-HCG resolution cannot be used as the end-point of expectant management of tubal ectopic pregnancy, which should be considered when counselling women and planning for future pregnancies., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to compare the success rate of methotrexate (MTX) treatment in patients with recurrent ectopic pregnancy (REP) and primary EP (PEP). A retrospective cohort study. The study cohort comprised all patients diagnosed with an EP and treated by intention with single-dose regimen of intramuscular MTX in a tertiary medical centre during 2010-2018. Cases (REP) and controls (PEP) were compared.262 patients had PEP and 32 had a REP. Women with REP had significantly higher gravidity order and higher incidence of previous abortions (5 vs. 3, median, p  < .001, 59.3% vs. 32.8%, p  < .001, respectively). Women with REP had a higher proportion of a history of previous surgery in general, and specifically pelvic surgery (46.8% vs. 20.6%, p  < .001, 24.4% vs. 7.2%, p  < .001, respectively). Treatment success was lower in the REP group (40.6% vs. 66.4%, p  = .006, Odds ratio 0.34, 95% confidence interval 0.16, 0.73). In a logistic regression analysis, the only factor found to be independently associated with treatment failure was REP (adjusted odds ratio 0.30, 95% confidence interval 0.12, 0.77, p  = .01). Our study suggests that medical treatment success with a single-dose regimen of MTX is lower than expected among REP cases, suggesting that different treatment approach should be considered in this setting.Impact statement What is already known on this subject ? There is paucity of data regarding success rate of methotrexate treatment for a recurrent ectopic pregnancy (REP). What do the results of this study add? Medical treatment success with a single-dose regimen of MTX in patients with a REP is lower than expected What are the implications of these findings for future clinical practice and/or further research? As medical treatment success with a single-dose regimen of MTX for women with a REP is lower than expected, different treatment approach should be considered. Further and prospective studies with a larger sample size are needed to confirm our findings.

Objective: To evaluate if a decreasing human chorionic gonadotropin (hCG) between day (D) 1 and D7 is an equal or better predictor of tubal ectopic pregnancy (EP) resolution following methotrexate (MTX) treatment than the current standard of care., Study Design: This was a retrospective cohort prognostic accuracy study of women with a transvaginal ultrasound (TVS)-confirmed tubal EP (November 2006-December 2015). After single-dose MTX treatment, D4/7 hCG ratios were compared with that of D1/D7 in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to predict EP resolution., Results: Tubal EP was diagnosed in 301/7350 (4.1%) women who underwent TVS for early pregnancy-related complaints. The patients were managed accordingly: expectant, 84/301 (27.9%); MTX, 65/301 (21.6%); surgery, 152/301 (50.5%). A D1/D7 hCG ratio ≤0.85 predicted successful resolution of tubal EPs (P < 0.001) treated with MTX with sensitivity 0.84 [95% confidence interval (CI), 0.69-0.94]), specificity 0.71 [95%CI, 0.48-0.89], PPV 0.84 [95%CI, 0.69-0.94], NPV 0.84 [95%CI, 0.69-0.94], which is comparable to the prognostic performance of the D4/7 protocol., Conclusion: In patients with tubal EP carefully selected for and treated with MTX, it may be reasonable to eliminate the D4 hCG in the follow-up algorithm., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Blood flow in the corpus luteum is associated with luteal function. However, the impact of luteal blood flow on methotrexate (MTX) treatment in women with unruptured tubal pregnancy has not been reported. The aim of the present study was to observe the impact of luteal blood flow on the therapeutic effect of MTX in women with unruptured tubal pregnancy., Methods: A prospective observational study recruited 129 women with unruptured tubal pregnancy in the First Affiliated Hospital of Xi'an Jiaotong University from September 2016 to June 2018. One hundred and fifteen women were treated successfully with MTX, and women were divided into 2 groups according to luteal blood flow: the poor luteal blood flow group and the abundant luteal blood flow group. The therapeutic effects were compared between the two groups., Results: Women in the abundant luteal blood flow group had a significantly higher serum β-human chorionic gonadotropin (β-hCG) level 4 days, 1 week and 2 weeks after MTX treatment compared with women in the poor luteal blood flow group (P < 0.05). The average diameter of the ectopic mass 1 week, 2 weeks and 3 weeks after MTX treatment in women with abundant luteal blood flow was significantly larger (P < 0.05), and the time of serum β-hCG clearance and ectopic mass disappearance were significantly longer compared with those in women in the poor luteal blood flow group (P < 0.05)., Conclusions: Luteal blood flow might be a predictive factor for MTX treatment outcomes in women with unruptured tubal pregnancy, and those with abundant luteal blood flow need a longer recovery time.

Bilateral tubal ectopic pregnancy is a very rare form of ectopic pregnancy. The incidence is higher in women undergoing assisted reproductive techniques or ovulation induction. We report the case of bilateral tubal ectopic pregnancy. The patient was 30 years old and had a 3-year history of infertility; she was referred to the in-vitro fertilization (IVF) program because of tubal factor infertility. A pregnancy resulted from the transfer of two embryos during an artificial cycle. Despite the increase in β-hCG values during the follow-up, 22 days after the embryo transfer, the β-hCG levels were 2,408 U/L and the serum progesterone (P4) level was 10.53 ng/ml. After application with methotrexate, β-hCG levels did not decrease effectively. Moreover, the sonographic screening revealed a suspicious bilateral tubal focus for ectopic pregnancy. A mini-laparotomy was performed and a bilateral tubal pregnancy was found. In the case of unilateral tubal pregnancy after the transfer of two embryos, the situation of the other tube should be systematically checked and β-hCG levels should be monitored., Competing Interests: The authors have no conflict of interests to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Expectant management of tubal ectopic pregnancies is a feasible and possibly preferable method of management in asymptomatic women with low serum β-human chorionic gonadotropin (hCG). This involves serial monitoring of β-hCG until negative, after which it is deemed as spontaneously resolved ectopic pregnancy. We describe a case of tubal ectopic pregnancy which was expectantly managed with an initial β-hCG of 585 mIU/mL until undetectable. This patient presented with ruptured ectopic pregnancy 8 weeks after the original diagnosis, at the level of 5 mIU/mL. This highlights the importance of close monitoring in the expectant management of tubal ectopic pregnancies, with the incorporation of imaging, even when serial β-hCG shows a persistently reducing trend., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tubal pregnancy is recognized as one of the most common ectopic pregnancy types. Salpingitis may result in tubal pregnancy by causing fallopian tube occlusion and hydrosalpinx. B cell activation factor (BAFF) is a proinflammatory cytokine that helps regulate both innate and adaptive immune responses. Our previous study firstly showed that BAFF immunostaining appeared on the cellular membrane and in the cytoplasm of tubal epithelial cells, and both BAFF protein and mRNA in human inflamed fallopian tubes had higher expression levels than those in normal fallopian tubes. This study aimed to elucidate the association between the expression of BAFF gene and the inflammation in the human fallopian tube leading to tubal pregnancy., Methods: We examined 70 patients undergoing salpingectomy for salpingitis (n = 35) and tubal pregnancy (n = 35). Twenty patients with benign uterine diseases undergoing complete hysterectomy and salpingectomy were recruited into control group. BAFF mRNA and protein in tissue samples were detected by qPCR and Western blotting methods. Furthermore, serum levels of BAFF, tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were measured using ELISA kits., Results: We found statistically significantly elevated expressions of BAFF mRNA or protein in whole tissue samples, and serum levels of BAFF, TNF-α and IL-6 in whole blood samples from patients with salpingitis and tubal pregnancy, in comparison to the control group., Conclusion: Based on the results, high expression of BAFF gene might induce inflammation in the human fallopian tube, suggesting its possible role in the tubal pregnancy process.

Objective: To investigate the clinical results and prognostic factors of multiple dose methotrexate (Mtx) treatment of ectopic pregnancy patients with high initial serum (human chorionic gonadotropin [hCG])., Design: Retrospective cohort study., Patients: Twenty-six ectopic pregnancy patients with serum (βhCG) > 5,000 mIU/mL who received multiple doses of Mtx (1 mg/kg) with folinic acid rescue on the alternating days., Results: Success rate was 88.5%. All failures were tubal ruptures in those who underwent surgery. Median initial hCG values of the success and the failure patients were 8,582 (5,058-31,114) and 5,280 (5,042-13,563) mIU/mL respectively (p > 0.05). Side effects were seen in 18 patients (69.2%, one bone marrow suppression and 17 minor side effects). The number of Mtx injections (7.04 ± 1.71), Mtx dose (71.35 ± 13.16 mg) and follow-up period (42.04 ± 23.77 days) did not differ between groups. Body mass index (BMI), Mtx dose, number of Mtx and change in βhCG levels between the initials and the levels measured 2 days after the 3rd, 4th, and 5th Mtx injections were found to be highly predictive for tubal rupture., Conclusions: Multiple-dose Mtx treatment of ectopic pregnancies with high initial hCG is safe and effective. BMI, Mtx dose, number of Mtx injections and the decrement of βhCG levels were found as highly predictive for the success of the treatment., (© 2018 S. Karger AG, Basel.)

Background: Consecutive measurements of β-hCG levels and sonographic evaluation of adnexae are critical for choosing the optimal management in ampullar tubal ectopic pregnancies (EP). To select suitable patients for conservative approach, there is a need for an affordable and reliable marker for determining rupture risk. Evaluation of systemic inflammatory markers in combination with serum β-hCG levels and ultrasound might help to decide the appropriate treatment option., Objective: The purpose of the present study was to evaluate the diagnostic value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in determining the rupture risk in ampullar tubal EPs and to compare with intraoperative findings., Methods: A total of 142 patients who underwent surgery for tubal EP were included. Seventy-two patients were in the intraoperatively diagnosed tubal rupture group and 70 patients without rupture findings were included in the control group. Both groups were compared for inflammation markers, β-hCG levels, and sonographic findings., Results: Both NLR and PLR levels were found to be significantly higher in the tubal rupture group (4.62 ± 3.13 vs. 2.67 ± 1.43, 162.94 ± 63.61 vs. 115.84 ± 41.15, p < 0.01, respectively). According to the receiver operating characteristic analysis performed for the diagnostic performance of tubal diameter measurement, β-hCG, NLR, and PLR levels were significantly associated with histopathologically confirmed tubal rupture (p < 0.01)., Conclusion: Systemic inflammatory markers are feasible and affordable tools for predicting tubal rupture risk in ampullar EPs and might be useful for determining surgery decision especially in low resource settings., (© 2019 S. Karger AG, Basel.)

Background: Unilateral twin tubal pregnancy is an extremely rare condition, occurring in 1/20.000-250.000 pregnancies and represents a major health risk for reproductive-aged women, leading to even life-threatening complications., Aim: We present a case of a 31-year-old woman with unilateral twin tubal pregnancy, treated with methotrexate and then surgically because of failure, followed by review of the literature., Methods: Researches for relevant data were conducted utilizing multiple databases, including PubMed and Ovid., Results: The most common type of twin ectopic pregnancy is the heterotopic (1/7000 pregnancies) in which in which both ectopic and intrauterine pregnancy occur simultaneously. Expectant, medical and surgical therapy have similar success rates in correctly selected patients. Two prospective randomized trials did not identify any statistically significant differences between groups receiving MTX as a single dose or in multiple doses. Among the 106 cases reported in literature, methotrexate was tried just in 4 patients (3 unilateral and 1 bilateral) before ours. Details are reported in the table 1., Conclusion: The recent shift in the treatment of singleton ectopic pregnancies to the less invasive medical therapy might apply even in the case of twin implants.

Objective: Methotrexate is an alternative treatment for tubal pregnancy. However, despite initial treatment, ∼15% of women eventually require surgery. This study aimed to identify the risk factors for medical treatment failure in tubal pregnancy and apply them to a risk prediction model., Study Design: This single-center retrospective cohort study included 123 participants initially treated medically for tubal pregnancy between January 2006 and December 2015. Logistic regression analysis was used to construct a risk prediction model (visually presented as a nomogram) for medical treatment failure. Model performance was assessed using discrimination and calibration. The medical treatment failure rate was 36.6%. The prediction model integrated the presence of a gestational sac, ectopic mass size, and follow-up β-human chorionic gonadotropin levels above cut-off values on days 4 and 7. The model used the following cut-off values: increased β-human chorionic gonadotropin levels by 1028.6 mIU/mL, 1.0457-fold higher than baseline level on day 4; and increased β-human chorionic gonadotropin levels by 1233 mIU/mL, 1.3025-fold higher than baseline level on day 7., Results: The corresponding areas under the receiver-operating characteristic curves were 0.8135 (95% confidence interval, 0.733-0.893) for the day 4 model and 0.8600 for the day 7 model (95% confidence interval, 0.788-0.932). Comparison of the day 4 and 7 models revealed no significant difference in their predictive abilities (P = 0.4318)., Conclusions: This model identified a substantial proportion of the participants who experienced medical treatment failure for tubal pregnancy. It was visualized as a nomogram, facilitating clinical application., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The purpose of this study was to evaluate the application of ultrasound elastography in the assessment of methotrexate (MTX) treatment for tubal pregnancy and the association with the elasticity score and human chorionic gonadotropin (hCG) concentration., Methods: A total of 73 cases of unruptured tubal pregnancy were diagnosed and treated systemically with MTX. The sonographic characters of conventional transvaginal sonography and elastography and serum hCG concentrations before and after MTX therapy were retrospectively reviewed and analyzed., Results: The mean elasticity score was statistically significantly lower for the ectopic tubal masses of the success group (mean ± SD, 2.58 ± 0.68) than for the failure group (3.33 ± 0.47) on day 7 (P < .001) and similar on day 0. The median elasticity score for the success group on day 7 was 3, and for the failure group, it was 4. When elasticity scores of 3 and 2 were used for the criterion of successful MTX treatment, the elastography had 94.5% sensitivity, 61.1% specificity, 88.1% positive predictive value, and 78.6% negative predictive value. Elastography of the ectopic masses and subsequent hCG concentration at 1 week after the MTX injection in the success group had a strong relationship., Conclusions: Our results suggest that transvaginal elastography was a useful tool in the evaluation of tubal pregnancy after pharmacologic management., (© 2017 by the American Institute of Ultrasound in Medicine.)

Objectives: This study identified patients who would benefit from an earlier additional medical intervention and/or continuing close surveillance even if commonly used parameters indicated sufficient medical treatment to determine markers of treatment failure., Materials and Methods: A retrospective analysis of patients with a preliminary diagnosis of ectopic pregnancy treated with the single-dose methotrexate protocol. Group 1: cases cured with a single dose of methotrexate; Group 2: cases who required more than one dose of methotrexate or surgery following the first dose. Demographics, clinical/sonographic findings, observation period, and β-human chorionic gonadotropin (hCG) levels were compared among the two groups. Thresholds were defined and a regression analysis was performed to define independent predictors of failure., Results: Data from 120 patients were analyzed: Group 1 (n = 92); Group 2 (n = 28). β-hCG levels measured at all time points, and day (0-4) and day (4-7) changes, presence of adnexial masses, and infertility were significantly different among the two groups. Only the day (0-4) and day (4-7) changes in β-hCG levels were independent predictors of failure., Conclusion: Day (0-4) thresholds or newly defined day (4-7) thresholds were not more sensitive than the conventional day (4-7) criteria. Day (0-4) β-hCG levels increased by more than 9.7% in half the patients who required additional methotrexate doses or surgery despite fulfillment of the conventional day (4-7) criteria. In contrast, no cases of treatment failure were observed if the day (0-4) decrease was >26.6%., (Copyright © 2017. Published by Elsevier B.V.)

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.

Objectives: Ectopic pregnancies are among the leading causes of maternal morbidity and mortality in both developed and emerging nations, but tests for early, accurate, and convenient detection are lacking., Study Design: Between January 2013 and February 2015, 504 women with tubal pregnancy were prospectively recruited, and their clinical characteristics were recorded. Samples of peritoneal fluid were collected by culdocentesis, and venous blood was drawn from the antecubital vein. In samples from each source, levels of the following biochemical markers were measured: cancer antigen 125 (CA125), human chorionic gonadotropin (hCG), progesterone, vascular endothelial growth factor, and creatine kinase., Results: The ratios of biochemical markers in the peritoneal fluid and in the blood (R p/v ) were calculated. The median of R p/v -CA125 and R p/v -hCG were significantly lower in the ruptured ectopic pregnancy group than in the unruptured group. The optimal cutoff value to detect ectopic pregnancy rupture was 401.5U/mL as the upper limit for peritoneal CA125, with a sensitivity of 93.5% and specificity of 74.2%. The optimal cutoff value was 18.7 as the upper limit in the peritoneal fluid/blood ratio (R p/v ) of CA125, with a sensitivity of 77.5% and specificity of 68.4%., Conclusions: In countries with poor access to laparoscopy, culdocentesis is useful. In this study, culdocentesis provided additional information for management of abdominal pain when laparoscopy is not available. The authors propose R p/v cutoff values that can be used conveniently and quickly to diagnose ruptured ectopic pregnancies and bleeding, enabling rapid and appropriate therapeutic responses., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Tubal abortion is characterized by the extrusion of an ectopic product of conception implanted in the fallopian tube through the abdominal ostium into the peritoneal cavity. It can be either complete or incomplete and may lead to severe bleeding. Recognition of a complete tubal abortion may be challenging but is essential because it allows conservative management which make possible preservation of tubal function and fertility without the need for further cytostatic therapy. A case of a 30 years-old woman admitted for lower abdominal pain is reported.The level of hCG was 659.2 mU/mL and transvaginal ultrasound reveled a fluid collection in the pouch of Douglas. Laparoscopy was subsequently performed for the suspicion of ectopic pregnancy with hemoperitoneum. Corroborating the hCG dynamics with the laparoscopic findings, the diagnosis of complete tubal abortion was established. The histopathological examination confirmed the presence of intermediate trophoblastic cells in the tissue collected during laparoscopy. Ultrasound examination helps recognition of hemoperitoneum but adds little value to the diagnosis of tubal abortion. Laparoscopic findings alone are only suggestive for complete tubal abortion but in combination with hCG dynamics, the diagnosis can be established. Conservative management might be sufficient in complete tubal abortion and ensures preservation of tubal function and fertility., (Celsius.)

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.)

Objective:: To evaluate the association between the depth of trophoblastic infiltration and serum vascular endothelial growth factorconcentration in patients with an ampullary pregnancy., Methods:: This prospective cross-sectionalstudy involved 34 patients with an ampullary ectopic pregnancy who underwent salpingectomy between 2012 and 2013. Maternal serum vascular endothelial growth factor concentrations were measured using Luminex technology. Trophoblastic invasion was classified histologically as follows: stage I, limited to the tubal mucosa; stage II, reaching the muscle layer; and stage III,involving the full thickness. The qualitative data were compared using Fisher's exact test. The nonparametric Kruskal-Wallis and Mann-Whitney tests were used to evaluate differences in serum vascular endothelial growth factor among the degrees of trophoblastic invasion. ROC curves were constructed to determine vascular endothelial growth factor cut-off values that predict the degree of tubal invasion based on the best sensitivity and specificity., Results:: Eight patients had stage I trophoblastic invasion, seven had stage II, and 19 had stage III. The median serum vascular endothelial growth factorconcentration was 69.88 pg/mL for stage I, 14.53 pg/mL for stage II and 9.08 pg/mL for stage III, with a significant difference between stages I and III. Based on the ROC curve, a serum vascular endothelial growth factor concentration of 25.9 pg/mL best differentiated stage I from stages II and III with asensitivity of 75.0%, specificity of 76.9%, and area under the curve of 0.798., Conclusions:: The depth of trophoblastic penetration into the tubal wall isassociated with serum vascular endothelial growth factor concentration in ampullary pregnancies., Competing Interests: No potential conflict of interest was reported.

Background: Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success., Objective: This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol., Study Design: A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol., Results: In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P = .011, P < .001, and P = .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P = .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution., Conclusion: In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication., (Copyright © 2016 Elsevier Inc. All rights reserved.)

As there are no specific non-invasive markers for the diagnosis of tubal ectopic pregnancy, our objective in the present study was to explore the role of inflammatory cytokines IL-6 and IL-8 in the diagnosis of ruptured tubal ectopic pregnancy. Twenty-eight women with tubal ectopic pregnancy, 31 patients with intrauterine abortion and 29 gestational age matched women having normal intrauterine pregnancy were included in the study. Five millilitre of blood was collected at the time of admission, serum was separated and stored at -70 °C for subsequent analysis of β hCG, IL-6 and IL-8 levels. The level of IL-6 was a significant increase in the women with tubal ectopic pregnancy compared to intrauterine abortion and normal pregnancy. IL-8 levels decrease significantly in the tubal ectopic pregnancy and in intrauterine abortion patients when compared with the normal pregnancy group. At the cutoff of 26.48 pg/ml IL-6 level predicted the tubal ectopic pregnancy with moderate accuracy. Therefore, it can be concluded that measurement of IL-6 may have relevance in the diagnosis of ectopic pregnancy as a novel inflammatory serum biomarkers.

Objective: The purpose of this study was to compare clinical outcomes of conventional laparoscopic surgery and laparoendoscopic single-site surgery (LESS) in the surgical treatment of tubal ectopic pregnancy., Material and Methods: A total of 156 patients were diagnosed with ectopic pregnancies by ultrasonography and serum β-human chorionic gonadotrophin (β-hCG) levels at Pusan National University Yangsan Hospital from January 2009 through December 2013. We excluded 28 patients who only received medical treatment, 15 patients who underwent surgery by laparotomy for severe hypovolemic shock, and 30 patients who presented with less than 1 L of hemoperitoneum. Of the 83 patients with massive hemoperitoneum, 38 patients had LESS performed while the remaining 45 patients underwent conventional laparoscopic surgery., Results: In this study, there were no statistically significant differences in clinical outcomes in either surgical method except for operative time. Operative time of LESS was significantly shorter than conventional surgery for patients with more than 500 mL of hemoperitoneum., Conclusion: LESS is a safe and feasible surgical approach in the treatment of tubal ectopic pregnancy. At the same time, LESS has been shown to be more effective than conventional laparoscopic surgery in handling massive hemoperitoneum of more than 1 L, which is a common complication of ectopic pregnancy., (Copyright © 2016. Published by Elsevier B.V.)

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.

The present authors analyzed patients' backgrounds and pre-surgical findings to clarify the risk factors of rupture of fallopian tubal pregnancy. The surgical findings 113 cases were clearly diagnosed as fallopian tubal pregnancy with or without rupture. Twenty-six cases of fallopian tubal pregnancy were ruptured and 87 cases were not ruptured at the time of operation. The risk factors of fallopian tubal rupture were assessed by Chi-square for independence test and multiple regression analysis. Obesity (BMI over 26), prior birth history, social welfare entitlement, ultrasonography findings of fetal heart movement, and pre-surgical serum beta-hCG level more than 3,000 mIU/ml patient were significantly higher risk in fallopian tubal rupture. Fertility treatment patient were at significantly lower risk for fallopian tubal rupture. Higher beta-hCG levels, especially >3,000 mIU/ml is associated with increased risk of fallopian tubal rupture in ectopic pregnancy.

Objective: To establish clearance curves for serum β -hCG in women with successfully expectantly managed tubal ectopic pregnancies., Design: Retrospective cohort study. Non- viable tubal ectopic pregnancy was diagnosed on transvaginal ultrasound. If initial serum β hCG was less than 5000 IU/L and patients were asymptomatic, expectant management was offered. Patients underwent serial β hCG measurements until serum β hCG was less than 20 IU/l, or the urine pregnancy test was negative., Setting: Early Pregnancy and Gynaecology Assessment Unit, Kings College Hospital, London (December 1998 to July 2006)., Patients: We included 161 women with diagnosed non-viable tubal ectopic pregnancy who underwent successful expectant management., Main Outcome Measure: Serum β hCG level., Results: Mean initial serum β- hCG was 488 IU/L (41 - 4883) and median serum β hCG clearance time was 19 days (5 - 82). The average half-life of β hCG clearance was 82.5 hours (±SD 50.2) in patients with steadily declining serum β- hCG levels compared to 106.7 hours (±SD 72.0) in patients with primarily plateauing β-hCG levels in the declining phase. However, these differences were not significant (p>0.05)., Conclusion: We identified a median follow-up of 19 days until serum β hCG clearance in women with tubal ectopic pregnancy and successful expectant management. Although non- significant, women with initially plateauing serum β hCG showed a longer follow-up time until clearance compared to women with steadily declining β hCG levels. This information may serve as a guideline enabling clinicians to predict the length of follow-up for women with tubal ectopic pregnancy and expectant management.

A total of 81 patients with an ampullary ectopic pregnancy undergoing salpingectomy were enrolled in the study. The ampullary pregnancies were classified according to the depth of trophoblastic infiltration into tubal wall as follows: Stage I, limited to mucosa; Stage II, extension to the tubal muscularis; Stage III, complete tubal wall infiltration up to the serosa. An association was observed between serum β-human chorionic gonadotropin (β-hCG) levels and the depth of trophoblastic infiltration. Significantly higher severe ischemic changes and rupture of tubal wall were observed in patients with stage III infiltration compared with the other groups. A significant association was found between the absolute depth of trophoblastic invasion and severe ischemic changes, and also rupture of serosa. In conclusion, serum β-hCG levels are associated with depth of trophoblastic invasion into the tubal wall, severe ischemic changes, and rupture of the tubal wall., (© The Author(s) 2015.)

Background: A subset of women with a tubal ectopic pregnancy can be safely managed expectantly. Expectant management involves a degree of disruption with hospital visits to determine serum β-hCG (β-human chorionic gonadotrophin) concentration until the pregnancy test becomes negative and expectant management is considered complete. The length of time required for the pregnancy test to become negative and the parameters that influence this interval have not been described. Information on the likely length of follow up would be useful for women considering expectant management of their tubal ectopic pregnancy., Methods: This was a retrospective study at a tertiary referral center in an inner city London Hospital. We included women who were diagnosed with a tubal ectopic pregnancy by transvaginal ultrasound between March 2009 and March 2014. During the study period 474 women were diagnosed with a tubal ectopic pregnancy and 256 (54 %) of them fulfilled our management criteria for expectant management. A total of 158 (33 %) women had successful expectant management and in those cases we recorded the diameter of the ectopic pregnancy (mm), the maximum serum β-hCG (IU/L) and levels during follow up until resolution as well as the interval to resolution (days)., Results: The median interval from maximum serum β-hCG concentration to resolution was 18.0 days (IQR 11.0-28.0). The maximum serum β-hCG concentration and the rate of decline of β-hCG were independently associated with the length of follow up. Women's age and size of ectopic pregnancy did not have significant effects on the length of follow up., Conclusion: Women undergoing expectant management of ectopic pregnancy can be informed that the likely length of follow up is under 3 weeks and that it positively correlates with initial β-hCG level at the time of diagnosis.

Purpose: To compare the effectiveness of expectant management versus methotrexate in selected cases of tubal ectopic pregnancy., Methods: A double-blind randomized trial included 23 selected patients with a confirmed diagnosis of tubal pregnancy who met the inclusion criteria (hemodynamic stability, initial serum β-hCG concentration <2,000 mIU/mL, declining titers of β-hCG 48 h prior to treatment, visible tubal pregnancy on transvaginal ultrasound, a tubal mass <5.0 cm and fertility desire). The patients were divided into two groups: 10 patients in the methotrexate group (MTX 50 mg/m(2) administered as a single intramuscular dose) and 13 patients in the placebo group (saline solution administered in a single intramuscular dose). Quantitative variables were expressed as means ± standard deviations and compared by Student's t test or Mann-Whitney test. Dichotomous variables (success/treatment failure) were presented as proportions and compared by the Fisher exact test., Results: Successful treatment with negative titers of β-hCG occurred in 9 cases (90.0%) of the methotrexate group and in 12 (92.3%) of the placebo group (p > 0.999). The β-hCG values became undetectable at 22 ± 15.4 days in the methotrexate group and 20.6 ± 8.4 days in the placebo group (p = 0.80)., Conclusion: This study showed no statistically significant difference between the treatment with methotrexate and placebo, with similar success rates and similar time interval for β-hCG to become undetectable.

Objective: To assess the association between ultrasound images and serum concentrations of vascular endothelial growth factor (VEGF) in ampullary pregnancies., Design: Prospective study., Setting: University hospital., Patient(s): Fifty patients with ampullary pregnancy., Intervention(s): Criteria for inclusion in the study were: singleton pregnancy from spontaneous conception; diagnosis of tubal pregnancy in the ampullary region; radical surgical treatment (salpingectomy); and measurement of serum VEGF, human chorionic gonadotropin, and progesterone on the day of surgery. An additional criterion was description of an ectopic mass by transvaginal ultrasound, as follows: [1] ectopic gestational sac containing an embryo with cardiac activity; and [2] tubal ring: a paraovarian formation similar to a gestational sac, not containing a viable embryo (an anechoic structure surrounded by a peripheral hyperechogenic halo); an empty ectopic gestational sac; a sac containing an embryo without cardiac activity; or a vitelline vesicle., Main Outcome Measure(s): Association between ultrasound images and serum concentrations of VEGF., Result(s): An association was found between ultrasonographic images and VEGF serum concentrations. Ectopic embryos with cardiac activity were associated with higher levels of serum VEGF., Conclusion(s): In ampullary pregnancy, higher serum levels of VEGF are associated with the finding of an embryo with cardiac activity on transvaginal ultrasound. Greater production of VEGF likely creates development conditions more conducive to ectopic embryos., (Copyright © 2015. Published by Elsevier Inc.)

Galectin-1 and galectin-3 are abundantly expressed at implantation sites in the uterus, suggesting their involvement in the establishment of pregnancy. In this study, we examined the expression and localization of galectin-1 and galectin-3 in fallopian tubes from nonpregnant women, and in those presenting with tubal ectopic pregnancy. There was no significant difference in the expression of either galectin-1 (LGALS1) or galectin-3 (LGALS3) transcripts in the fallopian tube across the menstrual cycle. Their expressions in the fallopian tube were inversely correlated to each other (r = -0.5134, p < 0.0001) and differentially localized. Galectin-1 protein was abundant in the stroma of nonpregnant fallopian tubes, whereas galectin-3 was mainly localized to the epithelium, notably to the cilia of ciliated cells and the apical cytoplasm of secretory cells. In ectopic pregnancies, LGALS3 expression was significantly reduced (p < 0.0001), but LGALS1 expression did not change when compared to nonpregnant fallopian tubes collected during the mid-secretory phase. The percentage of fallopian tube epithelial cells expressing galectin-3 in cilia tended to be reduced (p = 0.0685), with an accompanying loss of a normal ciliary structure, while nuclear galectin-3 increased (p < 0.05) in ectopic pregnancies. Epithelial immunostaining for galectin-1 tended to be elevated in fallopian tubes from women with ectopic pregnancy. Coculture of human trophoblast origin SW71 cells significantly increased LGALS1 expression in human fallopian tube epithelial OE-E6/E7 cells, suggesting that trophoblast-derived products regulate LGALS1 expression in the oviductal epithelium. These findings imply a differential contribution of galectin-1 and galectin-3 in the homeostasis of human fallopian tubes and in the pathophysiology of ectopic pregnancy., (© 2015 S. Karger AG, Basel.)

Objective: Ectopic pregnancy (EP) is the major cause of maternal morbidity and is responsible for maternal mortality in the first trimester. In order to reduce undesirable results, it is necessary to find rapid and accurate, non-surgical diagnostic tests for ER The goal of the study was to investigate the differences in complete blood count parameters between tubal EPs and healthy pregnancies in be used in the diagnosis of ectopic pregnancy., Study Design: White blood cell (WBC), neutrophil, monocyte, lymphocyte, platelet (PLT) counts, mean PLT volume (MPV) and PLT distribution width (PDW) levels in the complete blood count samples have been obtained from subjects with diagnosed tubal EP (n=78; study group) and women with healthy intrauterine gestations (n=79; control group). Statistical comparisons between groups were performed using the t test., Results: PDW levels were found to be significantly higher in the control group than EP (p<0.001). However no differences between the study and control groups with regard to PLT and MPV levels were observed. WBC levels were found to be significantly higher in the EP group as compared to controls (p<0.001). When leukocyte differentials were compared, monocyte counts in the EP group were significantly higher than in controls (p=0.005). No statistically significant differences in neutrophil and lymphocyte values were observed in either group., Conclusion: PDW as an indicator of PLT activation is lower in tubal EP than intrauterine pregnancy so, possibly endometrial invasion in the intrauterine pregnancy needs more PLT activation. Monocyte counts are higher in tubal EP, indicating that monocyte activation in the pathophysiology of EP could be effective in the formation of tubal motility and microenvironment regulation.

Background: In ectopic pregnancy (EP) management, failure of βhCG to fall more than 15% between Days 4 and 7 after methotrexate administration indicates the need for a second dose. Regimens preferring a 25% fall in βhCG between methotrexate administration and Day 7 have been proposed., Aims: Our study analysed these and other regimens' performance in predicting treatment success. Secondarily, we investigated how each regimen guided the prescription of additional methotrexate doses., Methods: Medical files of 88 women with ultrasound confirmed tubal EP and pretreatment βhCG <6000 IU/L, unsuitable for expectant management, were retrospectively analysed. The βhCG monitoring regimens studied were (i) 15% fall Day 4-7, (ii) 25% fall Day 0/1-7, (iii) any fall Day 0/1-7, (iv) any fall Day 0/1-4 and (v) 20% fall Day 0/1-4. Treatment success was defined if the EP resolved without surgical intervention. Statistical analysis was performed using McNemar's test., Results: Overall, treatment success with methotrexate was 92% (n = 81/88). Predicting success of methotrexate (PPV 98-100%) and detecting those needing surgery (specificity 86-100%) were equivalent across all monitoring regimens. However, the 25% Day 0/1-7 fall (and the Day 0/1-4 regimens) over-selected women for a second dose of methotrexate (P < 0.05)., Conclusion: The performance of each regimen is equivalent to the traditional 15% fall Day 4-7 regimen in predicting treatment success. However, a regimen aiming for a 25% fall in βhCG Day 0/1-7 over-selects patients for a second methotrexate dose. In comparison, any drop in βhCG Day 0/1-7 does not over-select women and eliminates Day 4 testing., (© 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Objective: To evaluate the depth of trophoblastic infiltration in tubal wall in ectopic pregnancy (EP) assessed by histopathology and their correlation with initial values of β-hCG., Methods: A prospective study including 27 patients with diagnosis of EP was realized. The tubal pregnancies were histologically classified according to the depth of infiltration of trophoblastic tissue on the wall of the tube (stage I: limited to mucosa; stage II: reaching the muscularis layer; stage III: complete infiltration of the tubal wall). The comparison between groups for numeric variables was performed by ANOVA. The receiver operating characteristic (ROC) curve was performed to obtain the cutoff value of β-hCG associated with the degree of trophoblast invasion into the wall of the tube evaluated by histology., Results: The mean β-hCG in patients evaluated by histopathology as stage I + II was 2868 mIU/ml and stage III was 11 202 mIU/ml (p = 0.017). β-hCG levels that best predicted for stage III was 2906 mIU/ml, with a sensitivity of 85.7% and a specificity of 69.2%., Conclusion: There is a direct correlation between serum β-hCG and the depth of trophoblast infiltration of the tube wall at histopathology.

Objectives: To determine whether the distribution of transvaginal sonographic findings of ectopic pregnancy has changed since the studies done 20 years ago and to explore the correlation of tubal rupture with transvaginal sonographic findings and human chorionic gonadotropin (hCG) levels., Methods: Patients with ectopic pregnancy who underwent transvaginal sonography before treatment were included. Sonograms and medical records were retrospectively reviewed. The presence of a tubal ring, the presence of a yolk sac, embryonic cardiac activity, the degree of vascularity on color Doppler imaging, hCG levels, and results of surgery were recorded., Results: Our study included 231 ectopic pregnancies. A positive sonographic adnexal finding was present in 219 cases (94.8%): adnexal mass in 218 (94.4%) and a moderate-to-large amount of free fluid in 84 (36.4%). The adnexal masses were graded as follows: 1, nonspecific mass (125 cases [54.1% of total]); 2, tubal ring without a yolk sac or embryo (57 [24.7%]); 3, yolk sac but no embryonic heartbeat (19 [8.3%]); and 4, embryo with cardiac activity (17 [7.4%]). The mean hCG level increased as the grade ascended from 1 to 4. Thirty-six patients had tubal rupture at surgery within 24 hours of the sonogram. A moderate-to-large amount of free fluid was significantly associated with tubal rupture (P < .05) but had low sensitivity, specificity, and positive predictive value for rupture. Other sonographic findings and hCG levels were not significantly related to tubal rupture., Conclusions: Transvaginal sonography showed an adnexal abnormality in nearly 95% of our patients with ectopic pregnancy, most commonly a nonspecific adnexal mass. Embryonic cardiac activity was seen in fewer than 10%. Neither sonographic findings nor hCG levels were useful predictors of tubal rupture.

Aim: The objective of this study was to review our experience with ectopic pregnancy management and to evaluate major predictive factors for failure of conservative linear salpingostomy., Methods: Seven hundred and ninety-seven cases that were treated for ectopic pregnancy in our clinic between October 2005 and September 2011 were analyzed retrospectively for incidence and treatment options. We defined failure as rising or plateauing postoperative serum β-hCG levels that required additional medical or surgical treatment after initial removal of the ectopic pregnancy by laparoscopy or by laparotomy. We examined the risk factors consisting of preoperative β-hCG, size and location of ectopic lesions, the presence of fetal heart beat and tubal condition that can influence the failure or success of conservative salpingostomy., Results: In total, 403 patients were treated conservatively. These conservative managements consist of 334 salpingostomies performed by laparoscopy and 69 by laparotomy. Because of persistent ectopic pregnancy, 16 patients underwent medical treatment. In total, 387 patients were treated successfully with conservative management and 16 patients were treated unsuccessfully with conservative management. When variables of P < 0.05 were subjected to multivariate analysis, size of the ectopic pregnancy of 33.5 mm or greater and fimbrial and isthmic region ectopic pregnancies were significantly associated with the failure rate., Conclusions: The size of the ectopic pregnancy and fimbrial and isthmic region ectopic pregnancies were determinant of failure of conservative surgery. Our success rate in the ruptured group is not an underestimated value to dissuade patients wishing to maintain fertility by undergoing salpingectomy. So, the conservative approach to ectopic pregnancy should be undertaken after careful patient evaluation., (© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.)