Combination of gefitinib and methotrexate to treat tubal ectopic pregnancy (GEM3): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Tubal ectopic pregnancies can cause substantial morbidity or even death. Current treatment is with methotrexate or surgery. Methotrexate treatment fails in approximately 30% of women who subsequently require rescue surgery. Gefitinib, an epidermal growth factor receptor inhibitor, might improve the effects of methotrexate. We assessed the efficacy of oral gefitinib with methotrexate, versus methotrexate alone, to treat tubal ectopic pregnancy. METHODS: We performed a multicentre, randomised, double-blind, placebo-controlled trial across 50 UK hospitals. Participants diagnosed with tubal ectopic pregnancy were administered a single dose of intramuscular methotrexate (50 mg/m2) and randomised (1:1 ratio) to 7 days of additional oral gefitinib (250 mg daily) or placebo. The primary outcome, analysed by intention to treat, was surgical intervention to resolve the ectopic pregnancy. Secondary outcomes included time to resolution of ectopic pregnancy and serious adverse events. This trial is registered at the ISRCTN registry, ISCRTN 67795930. FINDINGS: Between Nov 2, 2016, and Oct 6, 2021, 328 participants were allocated to methotrexate and gefitinib (n=165) or methotrexate and placebo (n=163). Three participants in the placebo group withdrew. Surgical intervention occurred in 50 (30%) of 165 participants in the gefitinib group and in 47 (29%) of 160 participants in the placebo group (adjusted risk ratio 1·15, 95% CI 0·85 to 1·58; adjusted risk difference -0·01, 95% CI -0·10 to 0·09; p=0·37). Without surgical intervention, median time to resolution was 28·0 days in the gefitinib group and 28·0 days in the placebo group (subdistribution hazard ratio 1·03, 95% CI 0·75 to 1·40). Serious adverse events occurred in five (3%) of 165 participants in the gefitinib group and in six (4%) of 162 participants in the placebo group. Diarrhoea and rash were more common in the gefitinib group. INTERPRETATION: In women with a tubal ectopic pregnancy, adding oral gefitinib to parenteral methotrexate does not offer clinical benefit over methotrexate and increases minor adverse reactions. FUNDING: National Institute of Health Research.

Safety of methotrexate administration in women with pregnancy of unknown location at high risk of ectopic pregnancy.

OBJECTIVES: To evaluate the safety of current guidelines on methotrexate (MTX) administration in women with pregnancy of unknown location (PUL) who are considered to have a high risk of underlying ectopic pregnancy (EP), and to investigate whether implementation of these guidelines would result in inadvertent exposure to MTX of viable intrauterine pregnancies (IUPs). METHODS: This was a retrospective observational study of consecutive clinically stable women who were classified with PUL at the early pregnancy unit of Nepean Hospital, Sydney, Australia, between 2007 and 2021. PUL was defined as a positive pregnancy test in the absence of signs of IUP or EP on transvaginal ultrasound. Patients with a PUL that behaved biochemically like an EP, but for which the location of pregnancy was not confirmed on ultrasound, were eligible for MTX to minimize the risk of subsequent tubal rupture. Criteria discussed in the guidelines of the American College of Obstetricians and Gynecologists (ACOG), American Society for Reproductive Medicine (ASRM), Royal College of Obstetricians and Gynaecologists (RCOG) and National Institute for Health and Care Excellence (NICE) were applied to the PUL database. The number of patients eligible to receive MTX and the number with an underlying viable IUP who would be inadvertently prescribed MTX were calculated. RESULTS: A total of 816 women with PUL were reviewed, of whom 724 had complete data and were included in the final analysis. Six patients had persistent PUL and the remaining 718 had a diagnosis of viable IUP, non-viable IUP, EP or failed PUL. According to the ACOG, ASRM, RCOG and NICE guidelines, the rate of MTX administration among patients with PUL would have been 2.76%, 4.56%, 0.41% and 35.36%, respectively. However, no persistent PUL would have received MTX according to the ACOG, ASRM and RCOG protocols (the NICE protocol identified patients with persistent PUL with a sensitivity of 100%), and the majority of MTX treatments were unnecessary because those patients were later classified as having non-viable IUP or failed PUL. Application of ACOG and ASRM guidance could result theoretically in inadvertent MTX administration to women with an underlying viable IUP at a rate of 4.1/1000 (3/724). CONCLUSIONS: Current guidelines used to predict high risk of EP in the PUL population lead to inadvertent MTX administration to women with an underlying viable IUP. These guidelines should be used wisely to ensure that no wanted pregnancy is exposed to MTX. Women with PUL should be monitored carefully, and MTX should be used judiciously when the location of pregnancy is yet to be confirmed. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A rare case of fundal intramural ectopic pregnancy associated with previous B-Lynch sutures.

BACKGROUND: Intramural ectopic pregnancy is a rare form of ectopic pregnancy that occurs within the myometrium. It is challenging to diagnose it early because of its nonspecific clinical presentation, and there is no consensus or guideline on the optimal management among gynecologists. CASE PRESENTATION: We report a case of a 34-year-old woman who developed fundal intramural ectopic pregnancy after a previous caesarean section with B-Lynch suture. The B-Lynch suture was performed at 38 weeks of gestation for postpartum hemorrhage caused by refractory uterine atony about 8 years ago. Since then, the patient had oligomenorrhea. The diagnosis of intramural ectopic pregnancy was not confirmed by magnetic resonance imaging or ultrasound. An exploratory laparoscopy and hysteroscopy was performed to remove the gestational sac without significant bleeding. The surgery was successful and the patient recovered well. The patient was advised to monitor her ß-HCG levels regularly until they returned to normal, and a follow-up pelvic ultrasound showed no complications. However, she has not been able to conceive or have an ectopic pregnancy so far. CONCLUSIONS: This case illustrates the difficulty of diagnosing intramural ectopic pregnancy, especially when it is associated with previous uterine surgery and B-Lynch suture. It also demonstrates the feasibility and safety of laparoscopic surgery for treating complete IUP, especially when the gestational sac is located close to the uterine serosa. However, the risk of uterine rupture and hemorrhage should be considered, and the patient should be informed of the possible complications and alternatives. Gynecologists should be familiar with various management strategies and customize the treatment plan according to the patient's clinical situation and preferences.

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.

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.

Evaluation of a scoring system to predict treatment success with single-dose methotrexate in ectopic pregnancy.

PURPOSE: This study sought to assess the efficacy of a newly developed scoring system in predicting treatment outcomes for ectopic pregnancy among patients undergoing single-dose methotrexate therapy. The primary research question centered on the reliability and predictive accuracy of objective parameters in determining methotrexate therapy success. METHODS: Conducted as a retrospective single-center cohort study, data from 172 ectopic pregnancy patients treated with methotrexate between January 2021 and January 2023 were analyzed. Parameters including adnexal mass size, peritoneal fluid presence, yolk sac identification, endometrial thickness, ectopic pregnancy location, and initial B-hCG levels were meticulously evaluated for their association with treatment outcomes. RESULTS: Following the exclusion of 21 emergency surgery cases, the final analysis comprised 151 patients. Notable associations were observed between specific parameters (fetal cardiac activity, adnexal mass size > 3.5 cm, peritoneal fluid presence, yolk sac identification, endometrial thickness > 10 mm, and initial B-hCG levels) and treatment outcomes (p < 0.001). Additionally, the novel scoring system demonstrated promising predictive performance. At a cutoff of 2.50, it achieved a sensitivity of 91.7% and a specificity of 59.7%. Increasing the cutoff to 3.50 resulted in a sensitivity of 94.0%, with a specificity of 46.3%. CONCLUSION: Objective parameters, particularly those integrated into the developed scoring system, exhibited substantial associations with methotrexate therapy outcomes in ectopic pregnancy. These findings underscore the potential of an objective scoring model to significantly influence clinical decision-making in therapy, offering avenues for enhanced prognostication and patient care in treatment outcomes.

Methotrexate vs expectant management for treatment of tubal ectopic pregnancy: An individual participant data meta-analysis.

INTRODUCTION: Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment. MATERIAL AND METHODS: We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times. TRIAL REGISTRATION NUMBER: PROSPERO: CRD42021214093. RESULTS: 1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group. CONCLUSIONS: Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.

Intra-amniotic and systemic administration of methotrexate with concomitant surgical evacuation of 11 + 5 weeks cervical ectopic pregnancy: a case report.

BACKGROUND: Cervical pregnancy is a rare type of ectopic pregnancy. The management of cervical pregnancy is challenging because of the rarity of the condition, late presentation, which is associated with increased risk of failed medical treatment, and excessive post-evacuation bleeding that may require hysterectomy. There is no good evidence in the literature regarding the pharmacological management of living cervical ectopic pregnancy of more than 9 + 0 weeks of gestation, and there is no standard protocol on methotrexate doses in these cases. CASE PRESENTATION: We present this case to describe a concomitant medical and surgical management of a living 11 + 5 weeks cervical pregnancy. The initial beta-human chorionic gonadotropins (ß-hCG) serum level was 108,730 IU/L. The patient received 60 mg of methotrexate intra-amniotically followed by another dose of 60 mg of methotrexate intramuscularly 24 h later. Fetal heartbeats stopped on day 03. On day 07, the ß-hCG was 37,397 IU/L. On day 13, the patient had evacuation of the remaining products of conception with the insertion of an intracervical Foley catheter to minimize the bleeding. On day 34, the ß-hCG was negative. CONCLUSION: The concomitant use of methotrexate to induce fetal demise along with surgical evacuation may be considered in the management of advanced cervical pregnancy to avoid excessive blood loss, and ultimately hysterectomy.

Rectal Ectopic Pregnancy Managed Successfully by Minimally Invasive Treatment Using Local Methotrexate Injection and Systemic Methotrexate Administration: An Extremely Rare Case at Tu Du Hospital in Vietnam and Literature Review.

Rectal ectopic pregnancy (REP) is one of the most extremely rare forms of ectopic pregnancy that strongly leads to maternal mortality higher than common types. An early diagnosis of unruptured REP remains a challenge and its management ought to be individualized depending on the clinical scenario. Currently, owing to the paucity of data, there are no practical guidelines for an appropriate treatment until today. We hereby present a very unusual case at our maternity care center. A 30-year-old pregnant woman (gravidity: 2, parity: 2) complained with abdominal pain and retard menstrual cycle. After serum beta-human chorionic gonadotropin (ß-hCG) levels and ultrasonic examinations, a diagnosis of ovarian ectopic pregnancy was established. Thus, the patient underwent explanatory laparoscopy for confirming the diagnosis and for the treatment. However, on the 5th day postoperative course, her ß-hCG level continued to increase every 48 hours. By magnetic resonance imaging and pelvic ultrasonography, a gestational sac adherent to the rectal wall was clearly detected. After counseling with multidisciplinary team, a minimally invasive laparoscopy followed by a local injection of methotrexate under ultrasound guidance for gestational sac access and a systemic multidose methotrexate regimen were indicated. In result, her serum ß-hCG declined substantially. Although it is very rare, extrauterine pregnancy involving the rectum may be presented. Early diagnosis helps in avoiding the fatal complications and a proper management should be counseled carefully. Conservative treatment with minimally surgical intervention could be an alternative option in appropriate condition. Further data are required to summarize this occult entity.

The Application Value of Contrast-Enhanced Ultrasonography in Assessing the Efficacy of Ultrasound-Guided Lauromacrogol Injections in Cesarean Scar Pregnancies.

OBJECTIVE: To investigate the application value of contrast-enhanced ultrasonography (CEUS) in ultrasound-guided lauromacrogol injections in patients with cesarean scar pregnancies (CSP). METHODS: A total of 31 patients diagnosed with CSP, who underwent an ultrasound-guided lauromacrogol injection + curettage in our hospital between February 2019 and December 2020 and had a complete recovery confirmed by a postoperative ultrasound review and serum ß-human chorionic gonadotropin (ß-hCG) assay, were enrolled as the study subjects. According to the volume of intraoperative blood loss and the duration of postoperative vaginal bleeding, the patients were divided into two groups, with 19 in the significantly effective group (Group A) and 12 in the effective group (Group B). The recorded clinical data, including age, duration of amenorrhea, number of pregnancies, number of deliveries, time since last cesarean delivery, number of cesarean deliveries, and preoperative serum ß-hCG levels, were retrospectively analyzed. The morphological indicators in CEUS before the lauromacrogol injection, as well as immediately and 12-24 hours after the injection, were compared between the groups. RESULTS: In Group A, the post-injection CEUS showed no enhancement, single strip enhancement, and sparse punctate enhancement, while in Group B, it showed a more irregular ring and local patch enhancement. In addition, the number of cases where the CEUS showed no enhancement 12-24 hours after the injection was more than that of the immediate CEUS after the injection. In Group A, four (21.1%) cases showed a single strip-like blood flow on the immediate postoperative CEUS, four (21.1%) cases showed a sparsely dotted blood flow on the immediate postoperative CEUS, and three cases turned into no enhancement 12-24 hours after the injection. A total of four cases in Group B showed that the contrast enhancement range 12-24 hours after the injection was reduced compared with that of the immediate contrast after the injection. CONCLUSION: Contrast-enhanced ultrasonography can guide the location selection of the lauromacrogol injection in patients with CSP, and its postoperative morphological indicators can adequately predict the therapeutic effect after curettage and guide clinical management.

The indication and treatment outcome predictors of mifepristone treating ectopic pregnancy.

OBJECTIVE: Ectopic pregnancy is a life-threatening disease and is an important cause of pregnancy-related mortality. MTX is the primary conservative treatment medicine of ectopic pregnancy, and mifepristone is also a promising medicine. Through studying the ectopic cases at the third affiliated hospital of Sun Yat-Sen University, the study aims to analyze the indication and treatment outcome predictors of mifepristone. METHODS: The data of 269 ectopic pregnancy cases treated with mifepristone during the year 2011-2019 were retrospectively collected. Logistic-regression analysis was used to analyze the factors affiliated with the treatment outcome of mifepristone. Then ROC curve was used to analyze the indication and predictors. RESULTS: Through logistic-regression analysis, HCG is the only factor related to the treatment outcome of mifepristone. The AUC of ROC curve predicting treatment outcome with pre-treatment HCG is 0.715, and the cutoff value of ROC curve is 372.66 (sensitivity 0.752, specificity 0.619). The AUC of 0/4 ratio predicting the treatment outcome is 0.886, and the cutoff value is 0.3283 (sensitivity 0.967, specificity 0.683). The AUC of 0/7 ratio is 0.947, and the cutoff value is 0.3609 (sensitivity 1, specificity 0.828). CONCLUSIONS: Mifepristone can be used to treat ectopic pregnancy. HCG is the only factor related to the treatment outcome of mifepristone. Patients with HCG less than 372.66 U/L can be treated by mifepristone. If HCG descends more than 67.18% on the 4th day or 63.91% on the 7th day, it is more likely to have a successful treatment outcome. It is more precise to retest on the 7th day.

Analysis of risk factors for patients with cesarean scar pregnancy treated with methotrexate combined with suction curettage.

PURPOSE: To analyze the predictive value of clinical and ultrasound parameters for treatment failure after administration of methotrexate (MTX) in combination with suction curettage (SC) in treatment of cesarean scar pregnancy (CSP) in the early first trimester. METHODS: In this retrospective cohort study, electronic medical records of patients diagnosed with CSP and initially treated between 2015 and 2022 with MTX combined with SC were reviewed and outcome data were collected. RESULTS: 127 patients met inclusion criteria. 25 (19.69%) required additional treatment. Logistic regression analysis indicated that factors independently associated with the need for additional treatment included progesterone level > 25 mIU/mL (OR: 1.97; 95% CI: 0.98-2.87, P = 0.039), abundant blood flow (OR: 5.19; 95% CI: 2.44-16.31, P = 0.011), gestational sac size > 3 cm (OR: 2.54; 95% CI: 1.12-6.87, P = 0.029), and the myometrial thickness between the bladder and gestational sac < 2.5 mm (OR: 3.48; 95% CI: 1.91-6.98, P = 0.015). CONCLUSIONS: Our study identified several factors which increase the need for additional treatment following the initial treatment of CSP with MTX and SC. Alternative therapy should be considered if these factors are present.

Early prediction of the failure of methotrexate treatment by Days 1-4 serum ß-hCG change and 48-hour pre-treatment increment inß-hCG.

To determine whether the change of serum ß-hCG levels between Days 1 and 4 and 48-h pre-treatment increment in ß-hCG can early predict treatment failure of single-dose methotrexate (MTX) in tubal ectopic pregnancies (EP), a retrospective study of 1120 ectopic pregnancies treated with a regimen of a single dose of MTX was conducted in the Department of Obstetrics and Gynaecology, Shanghai First Maternity and Infant Hospital. Treatment failure was defined by an obligation to proceed to surgery or have an additional doses of methotrexate.1350 files were reviewed, with 1120 included for final analysis .64% (722/1120) had ß-hCG levels increase on Day 4 after MTX treatment, while 36% (398/1120) had ß-hCG levels fall. In this cohort, the treatment failure rate with a single dose of MTX was 15.7% (113/722), and the significant features in the logistic regression model of diagnosing the results of MTX treatment were the ratio of Day 1 to Day 48-h pre-treatment ß-hCG values (Odds Ratio (OR) 1.221, 95% Confidence interval (CI) 1.159-1.294), the ratio of Day 4 to Day 1 ß-hCG serum values (OR 1.098, 95% CI 1.014-1.226), and ß-hCG values on Day 1 (OR 1.070, 95% CI 1.016-1.156). The decision tree model was developed by using increment of ß-hCG in 48 h before treatment > =19%, the ratio of Day 4 to Day 1 ß-hCG serum values > =36%, and ß-hCG values on Day 1> =728 mIU/L to predict the failure of MTX treatment. The diagnostic accuracy, sensitivity and specificity in the test group were 97.22%, 100%, and 96.9%, respectively.IMPACT STATEMENTWhat is already known on this subject? A decrease of 15% ß-hCG levels between Days 4 and 7 is a common protocol for predicting the success of a single-dose methotrexate therapy of an ectopic pregnancy.What do the results of this study add? This clinical study offers the cut-off values points for prediction of single-dose methotrexate treatment failure.What are the implications of these findings for clinical practice and/or further research? We identified the importance of ß-hCG increase between Days 1 and 4 and ß-hCG increment in 48 h pre-treatment for predicting the failure of single-dose methotrexate therapy. It can be used to aid the clinician to optimise the selection of the most appropriate treatment methods during a follow-up evaluation after MTX treatment.

Treatment of Cesarean Scar and Cervical Pregnancies Using the Ovum Aspiration Set for Intrachorial Methotrexate Injection as a Conservative, Fertility-Preserving Procedure.

Background and Objectives: Cesarean scar and cervical pregnancies are rare forms of ectopic pregnancies, occurring in 1 in 2000 and 1 in 9000 pregnancies, respectively. Both entities are medically challenging due to their high morbidity and mortality potential. Materials and Methods: In this retrospective study, we analyzed all cesarean scar and cervical pregnancies from 2010 to 2019 in the Department of Gynecology and Obstetrics of the University Hospital Freiburg, treated with both intrachorial (using the ovum aspiration set) and systemic methotrexate application. Results: We identified seven patients with a cesarean scar and four patients with cervical pregnancies. At diagnosis, the median gestational age was 7 + 1 (range: 5 + 5-9 + 5) weeks and the mean value of ß-hCG was 43,536 (range: 5132-87842) mlU/mL. On average, one dose of intrachorial and two doses of systemic methotrexate were administered per patient. The efficacy rate was 72.7% with three patients (27.3%) needing an additional surgical or interventional procedure. The uterus was preserved in 100% of the patients. Out of the eight patients with follow-up data, five reported subsequent pregnancies (62.5%) that resulted in six live births. None had recurrent cesarean scars or cervical pregnancies. In the subgroup analyses, when comparing cesarean scar pregnancies to cervical pregnancies, patient characteristics, treatment modality, and the outcome did not differ significantly, except for parity (2 versus 0, p = 0.02) and the duration since the last pregnancy (3 vs. 0.75 years, p = 0.048). When comparing cases with successful and failed methotrexate-only treatments, the maternal age was significantly higher in the successful group (34 vs. 27 years, p = 0.02). Localization of the gestation, gestational and maternal age, ß-hCG, and history of preceding pregnancies were non-predictive for the efficacy of the treatment. Conclusions: The combined application of intrachorial and systemic methotrexate for the treatment of cesarean scar and cervical pregnancies has been proven effective, well-tolerated, organ- and fertility-conserving with a low complication rate.

[Management of tubal ectopic pregnancies with methotrexate : is it an effective treatment ?] / La prise en charge des grossesses extra-utérines tubaires par méthotrexate : un traitement efficace ?

Ectopic pregnancy is a gynecological emergency. The hCG level, the clinical presentation and the ultrasound remain the key steps for the diagnosis. The criteria tend to be more and more codified to decide on the optimal treatment, however, there is no consensus. The aim of this study was to evaluate the impact of applying a mathematical formula to predict the failure rate of metho-trexate for tubal ectopic pregnancy. A retrospective, monocentric study was conducted on a cohort of 193 patients for whom the formula could be calculated. Regarding our professional practice, the success rate of first-line metho-trexate is 93 %. It would increase to 96 % if the formula had been applied. The use of the formula would also reduce the rate of first-line surgery by 12 %.

La grossesse extra-utérine est une urgence gynécologique. Le taux d'hCG, la clinique et l'échographie restent les examens clé pour le diagnostic. Les critères tendent à être de plus en plus codifiés pour décider du traitement optimal. Cependant, il n'existe aucun consensus. Le but de cette étude était d'évaluer l'impact de l'application d'une formule mathématique permettant de prédire le taux d'échec du méthotrexate pour une grossesse extra-utérine tubaire. Une étude rétrospective et monocentrique a été menée sur une cohorte de 193 patientes pour lesquelles la formule a pu être calculée. Concernant notre pratique professionnelle, le taux de réussite du méthotrexate en 1ère intention est de 93 %. Il passerait à 96 % si la formule avait été appliquée. L'emploi de la formule permettrait également de diminuer de 12 % le taux de chirurgie réalisée en première intention.

Efficacy of In Situ Methotrexate Injection in the Treatment of Nontubal Ectopic Pregnancies: A Retrospective Multicenter Study.

STUDY OBJECTIVE: Evaluation of the efficacy of different injection sites of methotrexate in the treatment of nontubal ectopic pregnancies. DESIGN: Retrospective multicenter study. SETTING: Multicenter, including 3 teaching hospitals, an intercommunal hospital, and a clinic. PATIENTS: A total of 106 patients with nontubal ectopic pregnancies, including 59 interstitial, 39 cesarean scar, and 8 cervical or isthmic. INTERVENTIONS: Overall, 58 patients received methotrexate via intramuscular injection (IM group), 35 received methotrexate via in situ injection (IS group), and 13 received a combination of both in situ and intramuscular injections of methotrexate (IS + IM group). MEASUREMENTS AND MAIN RESULTS: The main end point of this study was measured via the primary success rate (defined as a negative ß-human chorionic gonadotropin level without recourse to any additional treatment) of treatment with methotrexate according to injection site. The primary success rate was 46.55% in the IM group, 60% in the IS group, and 61.54% in the IS + IM group, respectively. In the multivariate analysis, the primary success rate of treatment was significantly correlated to the in situ injection of methotrexate, either solely or in conjunction with an intramuscular injection of methotrexate administered the following day, (odds ratio = 2.7; 95% confidence interval, 1.03-7.14). CONCLUSION: Solely an intramuscular injection of methotrexate is a less efficient first-line treatment strategy for the conservative management of nontubular ectopic pregnancy. The use of an in situ injection of methotrexate should therefore be preferred.

Methotrexate versus expectant management in ectopic pregnancy: a meta-analysis.

BACKGROUND: Ectopic pregnancy (EP) affects 1-2% of all pregnant females'(Barnhart et al., Expert Opin Pharmacother 2(3):409-417, 2001) that can require emergent surgical intervention. Noninvasive diagnostic tests like transvaginal ultrasound (TVUS), and serial ß-hCG levels have enabled early diagnosis and allowed medical therapy to be tried. Methotrexate (MTX) versus expectant management, both have been considered safe but superiority of one over the other is lacking. METHODS: We searched for RCT that have shown efficacy of MTX versus expectant management in hemodynamically stable patients. Our primary outcome was whether one modality is superior to the other. RESULTS: Four RCT were included in the meta-analysis after review. Our pooled analysis when comparing MTX and expectant management showed us that the difference between the uneventful decline in ß-hCG levels (treatment success) was statistically insignificant (RR = 1.06, 95% CI 0.93-1.21) with no significant heterogeneity between trials (I2 = 0.0%, P = 0.578). The difference between need for surgical intervention between methotrexate and expectant management was also statistically insignificant (RR = 0.77, 95% CI 0.43-1.40) with no significant heterogeneity between trials (I2 = 0.0%, P = 0.552). CONCLUSION: We conclude that expectant management is not inferior to MTX in hemodynamically stable patients with ectopic pregnancy that have declining or low ß-hCG levels.

Endovascular treatment of cesarean scar pregnancy: a retrospective multicentric study.

PURPOSE: To assess the role of Uterine Artery Embolization (UAE) to treat cesarean scar pregnancy (CSP) using different embolic materials, focusing on its clinical and technical success rates; the association of UAE with methotrexate (MTX) and/or dilatation & curettage (D&C) was evaluated also. MATERIALS AND METHODS: A retrospective analysis 33 patients (mean age 35 years) affected by CSP and treated with UAE from March 2012 to 2020 was performed. Dynamic levels of serum ß-HCG have been collected until they decreased to normal values after procedures. For the statistical analysis the sample was divided into 2 groups: UAE versus UAE + MTX. RESULTS: The gestational sac age ranged between 5 and 13 weeks (mean 7 weeks). According to operator's preference, 11 patients (33.33%) were treated with sponge injection, 2 patients (6.06%) with a combination of sponge and microsphere the remaining 20 patients (60.60%) with microspheres alone. No major complications occurred after UAE and D&C, neither side effects related to the MTX administration. Technical and clinical success rates were 97% and 85%, respectively. Mean percentage of ß-HCG reduction was 90% (range - 99.92 to + 7.98%). Statistical analysis with linear regression shows a R2 value of 0.9624 in UAE group while a R2 value of 0.9440 in UAE + MTX group with statistical significance (p < 0.0001). No significative differences were found between the two groups about clinical success rate and embolic material adopted. CONCLUSION: In this series UAE has been found to be safe and effective for the treatment of CSP.

Conservative management of a viable cervical ectopic pregnancy with systemic and multiple local methotrexate injections. A case report.

PURPOSE: Cervical ectopic pregnancy is rare and has serious haemodynamic implications, usually requiring a hysterectomy. However, the patient's haemodynamic profile and reproductive history may warrant medical management with methotrexate. We present a case report of a 33-year-old primigravida managed conservatively (patient insisted) for cervical ectopic pregnancy. MATERIALS AND METHODS: A 10-weeks pregnant lady suffered from cervical pregnancy as confirmed by ultrasonography with initial ß-HCG titre = 65,928 mIU/mL. She received a methotrexate IM-injection followed by multiple transabdominal-ultrasound-guided local doses. Serial sonography to monitor gestational sac size and ß-HCG levels were done weekly. RESULTS: ß-HCG levels declined satisfactorily over 4 weeks: 19,166 mIU/mL, 6900 mIU/mL and 1104 mIU/mL on days 14, 21 and 28, respectively. She remained haemodynamically stable throughout admission. On day-35, ß-hCG titre reached 400 mIU/mL, and products of conception seen on ultrasound (20 × 25 mm), that were later complicated by secondary infection, necessitated evacuation curettage. ß-HCG titre was 2 mIU/mL by 48th day. CONCLUSIONS: Live cervical ectopic pregnancy with high ß-hCG titres can be conservatively managed with multidose methotrexate injection administered systemically and locally. However, the efficacy of the applied dose of 25 mg or using higher doses should be evaluated to avoid occurrence of residual lesion.

Perspectives of health care providers regarding the levonorgestrel-releasing intrauterine system.

OBJECTIVES: The aims of the study were to assess the number of insertions per month of the 52 mg levonorgestrel-releasing intrauterine system (LNG-IUS) and gauge the knowledge and opinions of health care providers with regard to some of its characteristics and the reasons why women liked using the method. METHODS: An online questionnaire survey was conducted between January and July 2021 at the University of Campinas, Brazil. The survey comprised physicians and nurses from centres that had requested and received donated devices. RESULTS: A total of 65 health care providers answered the questionnaire (41 physicians and 24 nurses). The main misconceptions were related to insertion after an ectopic pregnancy: 60/65 (92.3%) answered that users with previous ectopic pregnancy must have frequent follow-up. Wrong answers were also given on the occurrence of acne (37/65, 56.9%) and depression (32/65, 49.2%). Participants reported that the LNG-IUS was highly effective (100%), long-acting (93.9%) and an appropriate method for controlling uterine bleeding (90.8%) and that it had few side effects (86.2%). CONCLUSION: Our study suggests that health care providers from centres that requested and received LNG-IUS donations, even though they reported adequate knowledge about the device, still had misconceptions with regard to its clinical management.