Can failure be predicted in methotrexate treatment with the modified parameter?

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 (ß-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 ß-hCG was 1976 in the methotrexate group and 2358 in the surgery group (p < 0.05). The ROC curve determined the effect of BW (ß-hCGxWBC/1000) and BP (ß-hCGx1000/PLT) markers in diagnosing patients who will need surgery in ectopic pregnancy. The areas under the ROC curve for ß-hCG, BW and BP were 0.86, 0.99 and 0.94, respectively (p < 0.05). ß-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 ß-hCG are effective in predicting ectopic pregnancy patients who may undergo surgery.

Diagnostic utility of clinicodemographic, biochemical and metabolite variables to identify viable pregnancies in a symptomatic cohort during early gestation.

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 ß (ß-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 ß-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.

Relationship of Beta-Human Chorionic Gonadotropin to Ectopic Pregnancy Detection and Size.

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 (ß-hCG) level to qualify for diagnostic testing (pelvic ultrasound) can delay diagnosis and treatment. In this study we sought to determine the relationship between ß-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 ß-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 ß-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 ß-hCG levels less than 1,500 mIU/mL. Comparison of size of ectopic pregnancy (based on maximum dimension in millimeters) to ß-hCG levels revealed a very weak correlation (r = 0.144, P < .001), and detection of ectopic pregnancies by ultrasound was independent of ß-hCG levels. Conclusion: Levels of ß-hCG do not correlate with the presence or size of an ectopic pregnancy, indicating need for diagnostic imaging regardless of ß-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.

Evaluation of the parameters in predicting single-dose methotrexate therapy success for ectopic pregnancy.

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 ß-hCG level ratio. METHODS: Retrospective cohort study was conducted within patients diagnosed with tubal ectopic pregnancy. Patients' characteristics, ultrasound findings, laboratory data, and ß-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/m2). 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 ß-hCG levels on admission (1128 and 4125 mIU/mL) and the day 4 to day 1 ß-hCG ratio (0.91 and 1.25). The overall MTX success rate was 79%, reaching 93% and 89% for ß-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 ß-hCG (sensitivity 70.3% and specificity 68.5%) and a day 4 to day 1 ß-hCG ratio of 95.5% (sensitivity 84.7%, specificity 72.5%, positive predictive value 75.4%) for predicting MTX success. CONCLUSION: Establishing a ß-hCG cutoff can reduce hospital stay. The day 4 to day 1 ß-hCG ratio holds promise as a widely applicable predictor for MTX success or for determining MTX administration on day 4.

Evaluating cut-off levels for progesterone, ß human chorionic gonadotropin and ß human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study.

INTRODUCTION: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and ß human chorionic gonadotropin (ßhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, ßhCG, and ßhCG 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 ßhCG 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, ßhCG, and ßhCG ratio. RESULTS: Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for ßhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had ßhCG 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 ßhCG 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 ßhCG ratio. Although the median ßhCG 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 ßhCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation. CONCLUSIONS: Cut-off levels for ßhCG, ßhCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although ßhCG ratio and progesterone have slightly better performance in comparison, single ßhCG used in this manner is highly unreliable.

Ultrasound characteristics, serum biochemistry and outcome of ectopic pregnancies presenting during COVID-19 pandemic.

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.

Management of Cervical Ectopic Pregnancies: A Scoping Review.

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 ß-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 ß-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, ß-hCG level, size of pregnancy, and fetal cardiac activity but may benefit from a planned multimodal approach.

The relationship between serum thiol levels and thiol/disulfide homeostasis in women with tubal ectopic pregnancy.

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.

Ectopic pregnancy: a single-center experience over ten years.

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, ß-human chorionic gonadotropin (ß-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 ß-HCG level and LOS, with a linear regression ß coefficient of 0.01 and a P-value of 0.04. CONCLUSION: EP is a relatively common condition affecting approximately 1% of all pregnancies. ß-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.

Scar Pregnancy and Extrauterine Implants.

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 ß-human chorionic gonadotropin (ß-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.

The diagnostic utility of placental growth factor in ectopic pregnancy.

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.

Cesarean scar pregnancy: Two case report and therapeutic management algorithm.

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.

Lung neoplasm mimicking as ectopic pregnancy due to paraneoplastic secretion of human chorionic gonadotropin: a case report and literature review.

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 ß-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 ß-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.

Combination of conservative treatment and temporary bilateral laparoscopic uterine artery clipping with hysteroscopic transcervical resection for cervical pregnancy: A retrospective study.

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.

Actualización del enfrentamiento y manejo del embarazo ectópico tubario / Update of the confrontation and management of tubal ectopic pregnancy

INTRODUCCÍÓN Y OBJETIVOS: El embarazo ectópico es una condición potencialmente mortal, con una incidencia del 1 al 2%. El 97% se produce en las tubas uterinas, y el 80% de éstos se encuentran en la región ampular. El objetivo de esta revisión es exponer una actualización del enfrentamiento y manejo del embarazo ectópico tubario. MÉTODOS: Mediante el uso de la base de datos Epistemonikos, Scielo, Cochrane y Pubmed, se revisó la literatura existente sobre embarazo ectópico tubario. RESULTADOS: El diagnóstico de embarazo ectópico tubario implica una combinación de síntomas clínicos, serología y ultrasonido. El manejo médico es una opción segura y efectiva en la mayoría de las pacientes hemodinámicamente estables. En caso de fracaso de tratamiento médico, paciente incapaz de mantener seguimiento, embarazo ectópico roto o embarazo heterotópico, debe ser manejado con tratamiento quirúrgico idealmente por laparoscopía. Independiente del tratamiento utilizado, existe gran probabilidad de éxito y escasas complicaciones. CONCLUSIONES: Esta actualización describe la incidencia, factores de riesgo, diagnóstico, y manejo del embarazo ectópico tubario. Es importante un diagnóstico y tratamiento temprano, para reducir complicaciones asociadas a esta patología.

INTRODUCTION AND OBJECTIVES: Ectopic pregnancy is a potencially lethal condition, it has an incidence of 1-2%. 97% occurs in uterine tubes, and 80% in the ampulla. The objetive of this review is to update management of this pathology. METHODS: Existent literature was reviewed in different data base: Epistemonikos, Scielo, Cochrane and Pubmed. RESULTS: Tubal Ectopic Pregnancy Diagnostic implies a combination of clinical features, serology and ultrasound. Medical management is a safe and effective alternative in most of hemodinamically stable patients. When medical treatment fails, or patient is not able to stay in observation, or ectopic/heterotopic pregnancy is diagnosed, surgical management is needed specially by laparoscopy. Regardless of the treatment, there is a high chance of success and low rate of complications. CONCLUSIONS: This update describes incidence, risk factors, diagnostic and management of tubal ectopic pregnancy. An early diagnostic and treatment are crucial to reduce complications due to this pathology.

Predictors and clinical features of methotrexate (MTX) therapy for ectopic pregnancy.

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 (ß-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 ß-hCG concentration less than 4000 IU/L was significantly higher than that of the group with an initial ß-hCG concentration greater than 4000 IU/L. However, the success rate of the group with an initial ß-hCG concentration greater than 4000 IU/L was still relatively high (54.55%). ß-hCG levels were significantly increased on the 4th day in the failed treatment group (P = 0.000). Compared to the initial ß-hCG level, the day-4 ß-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 ß-hCG level or adnexal mass size. The change in the ß-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.

The role of day 0 and day 4 ß-human chorionic gonadotropin values and initial ultrasound findings in predicting the success of methotrexate treatment in ectopic pregnancy.

OBJECTIVES: To determine the role of baseline ultrasound findings and the changes between ß- 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 ß-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 ß-hCG values at the time of admission and D4 and D7 ß-hCG values were compared. RESULTS: The success rate of single-dose methotrexate treatment was 77.2%. In the successful treatment group, the initial ß-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 ß-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.ß-hCG changes between D0-D4 may be advantageous in the clinical management of ectopic pregnancy for earlier evaluation.

Exosomal MicroRNAs in Serum as Potential Biomarkers for 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.

External validation of risk prediction model M4 in an Australian population: Rationalising the management of pregnancies of unknown location.

BACKGROUND: The prediction model M4 can successfully classify pregnancy of unknown location (PUL) into a low- or high-risk group in developing ectopic pregnancy. M4 was validated in UK centres but in very few other countries outside UK. AIM: To validate the M4 model's ability to correctly classify PULs in a cohort of Australian women. MATERIALS AND METHODS: A retrospective analysis of women classified with PUL, attending a Sydney-based teaching hospital between 2006 and 2018. The reference standard was the final characterisation of PUL: failed PUL (FPUL) or intrauterine pregnancy (IUP; low risk) vs ectopic pregnancy (EP) or persistent PUL (PPUL; high risk). Each patient was entered into the M4 model calculator and an estimated risk of FPUL/IUP or EP/PPUL was recorded. Diagnostic accuracy of the M4 model was evaluated. RESULTS: Of 9077 consecutive women who underwent transvaginal sonography, 713 (7.9%) classified with a PUL. Six hundred and seventy-seven (95.0%) had complete study data and were included. Final outcomes were: 422 (62.3%) FPULs, 150 (22.2%) IUPs, 105 (15.5%) EPs and PPULs. The M4 model classified 455 (67.2%) as low-risk PULs of which 434 (95.4%) were FPULs/IUPs and 21 (4.6%) were EPs or PPULs. EPs/PPULs were correctly classified with sensitivity of 80.0% (95% CI 71.1-86.5%), specificity of 75.9% (95% CI 72.2-79.3%), positive predictive value of 37.8% (95% CI 33.8-42.1%) and negative predictive value of 95.3% (95% CI 93.1-96.9%). CONCLUSIONS: We have externally validated the prediction model M4. It classified 67.2% of PULs as low risk, of which 95.4% were later characterised as FPULs or IUPs while still classifying 80.0% of EPs as high risk.

Outcome of cesarean scar pregnancy treated with local methotrexate injection.

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.