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.

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 treatment for peritoneal trophoblastic implants after laparoscopic salpingectomy and secondary laparoscopic excision of ectopic pregnancy.

Ectopic pregnancy is a one of the primary causes of maternal mortality in first trimester. The most common site of ectopic pregnancy is the fallopian tube. Surgical management of tubal ectopic pregnancy includes salpingotomy or salpingectomy. Persistent ectopic pregnancy can happen after salpingotomy due to incomplete removal of ectopic tissue. However, it is very rare after salpingectomy. In our case, the patient had right-sided salpingectomy and histology confirmed right-sided tubal ectopic pregnancy. She presented 19 days' later with abdominal pain, haemoperitoneum and persistent high beta-HCG (B-HCG). A second laparoscopy was done and tissue implants were removed from the surface of the right ovary and the omentum, which were confirmed to be products of conception on histology. The pain settled postoperative. However, B-HCG remained high postoperative. Subsequently, methotrexate treatment was given leading to full resolution of the pregnancy with one dose.

Day 4 and day 0 neutrophil-to-lymphocyte ratios as predictors of treatment failure with single-dose methotrexate for ectopic pregnancies.

OBJECTIVE: To evaluate changes in the neutrophil-to-lymphocyte ratio (NLR) between day 4 and day 0 in ectopic pregnancy (EP) patients treated with single-dose methotrexate (MTX) and investigate its predictive value for treatment outcome. METHODS: A total of 406 EP patients receiving single-dose MTX therapy at Shanghai First Maternity and Infant Hospital from January 10, 2013 to September 30, 2019 were studied. A multivariate model was constructed to predict treatment outcome. RESULTS: Among the 406 patients, 281 were treated successfully. Treatment success declined significantly when NLR decreased by less than 23% (74.8% vs 58.5%, P = 0.004). Multivariate regression analysis identified NLR reduction of less than 23% on day 4 (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.27-3.44), a human chorionic gonadotropin (hCG) decrease of 15% or less (OR 3.17, 95% CI 1.62-6.34), and an hCG increase of more than 15% on day 4 (OR 5.47, 95% CI 3.05-10.22) as independent risk factors for single-dose MTX treatment failure. The final predictive model had a sensitivity of 0.768 and a specificity of 0.569, using a cut-off value of 3. The area under the receiver operating characteristic curve was 0.712. Patients with a predictive score of ≥3 were more likely to fail single-dose MTX therapy. CONCLUSION: The present study concluded that an NLR decrease of less than 23% on day 4, a plateau or increase in serum hCG on day 4, and an hCG value greater than 1000 mIU/mL on day 0 were predictors of single-dose MTX treatment failure in EP patients.

[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.

Ectopic pregnancy adjacent to iliac vessels managed successfully by minimally invasive treatment using local methotrexate injection: An extremely rare case and literature review.

A case report of successfully treated retroperitoneal ectopic pregnancy (REP) is presented. A 36-year-old woman, gravida 3, para 2, was admitted to hospital for suspected ectopic pregnancy with light vaginal bleeding and mild abdominal pain for 3 days at 45 days of gestation by the last menstrual period.Multiple transvaginal ultrasonography and two times laparoscopic probes led to the diagnosis of REP located to the iliac blood vessels closely. Eventually the patient was cured with the treatment using local methotrexate injection under real-time ultrasound guidance and systemic methotrexate administration. We also summarized another 31 cases of REP to further understand this disease, sharing them to arouse clinical attention for the diagnosis and treatment of REP timely.

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.

Risk factors and prediction of ectopic pregnancy rupture following methotrexate treatment: A retrospective cohort study.

OBJECTIVE: Ectopic pregnancy (EP) rupture after methotrexate (MTX) treatment can have severe consequences. We examined clinical characteristics and beta-hCG trends that may predict EP rupture after MTX treatment. STUDY DESIGN: In this 10-year retrospective study of 277 women with an EP, we compared clinical, sonographic and beta-hCG trends, before and after MTX treatment, between those who did and did not have an EP rupture after MTX treatment. RESULTS: EP rupture was diagnosed in 41 women (15.1%) within 25 days of MTX treatment, and was correlated with higher parity and advanced pregnancy age: 2(0-5) vs. 1(0-6), P = 0.027 and 6.6(4.2-9.8) vs. 6.1(4-9.5), P = 0.045. EP rupture was also correlated with higher beta-hCG levels on days 0, 4 and 7 of MTX treatment: (2063 vs. 920 mIU/ml), (3221 vs. 921 mIU/ml) and (2368 vs. 703 mIU/ml), respectively, P < 0.001, for all. An increase of beta-hCG by>14% during days 0-4 showed a sensitivity of 71.4% CI 95% [55.4%-84.3%] and a specificity of 67.5% CI 95% [61.1%-73.6%] for predicting EP rupture after MTX treatment. Beta-hCG > 910 mIU/ml on day 0 showed a sensitivity of 80.9% CI 95% [66.7%-90.8%] and a specificity of 70.4% CI 95% [64.1%-76.3%] for predicting EP rupture after MTX treatment. A beta-hCG increase by>14% during days 0-4, and a beta-hCG value > 910 mUI/mL on day 0 were associated with increased risks of EP rupture after MTX treatment; the odds ratios were 6.4 and 10.5, respectively. Odds ratios were 8.06 [CI 95% (3.70-17.56)], P < 0.001 for every percent rise in beta-hCG during days 0-4; 1.37 [CI 95% (1.06-1.86)], P = 0.046 for every week change in gestational age; and 1.001 [CI 95% (1.000-1.001)], P < 0.001 for every unit rise in beta-hCG at day 0. CONCLUSION: Beta-hCG > 910 mIU/ml at day 0, a rise in beta-hCG by>14% during days 0-4, and more advanced gestational age were associated with EP rupture after MTX treatment.

Evidence-based complementary and alternative medicine conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility: A systematic review and meta-analysis.

BACKGROUND: Chinese medicinal retention enemas have gradually attracted the attention of clinicians as an alternative approach for tubal obstructive infertility. The purpose of this study was to investigate the efficacy and safety of conventional surgery combined with traditional Chinese medicinal retention enemas for the treatment of tubal obstructive infertility. MATERIALS AND METHODS: Eight electronic databases were searched from their inception to November 30, 2022. To assess the efficacy and safety of different treatments, following outcomes were measured: clinical pregnancy rate, clinical total effective rate, incidence of ectopic pregnancy, the improvement of Traditional Chinese Medicinal (TCM) symptoms, the improvement of the signs of obstructive tubal infertility and side effects. RESULTS: A total of 23 Randomized Controlled Trials (RCTs) with 1909 patients met the inclusion criteria. The pooled results showed a higher pregnancy rate in the experimental group than in the control group (RR 1.75, 95% CI [1.58, 1.94], Z = 10.55, P<0.00001). The clinical total effective rate in the experimental group was higher than that in the control group (RR 1.28, 95% CI [1.23, 1.34], Z = 11.07, P<0.00001). The incidence of ectopic pregnancy in the experimental group was lower than that in the control group (RR 0.40, 95% CI [0.20, 0.77], Z = -2.73, P = 0.01). CONCLUSION: Based on current evidence, we concluded that conventional surgery combined with traditional Chinese medicinal retention enema for tubal obstructive infertility was superior to conventional surgery alone in improving the clinical pregnancy rate, improving clinical total effective rate, improving TCM symptoms, improving the signs of obstructive tubal infertility and lowering the incidence of ectopic pregnancy. However, further clinical trials with high-quality methodologies need to be conducted.

Subsequent pregnancy outcomes among women with tubal ectopic pregnancy treated with methotrexate.

Lay summary: An ectopic pregnancy occurs when an embryo implants outside of the uterus, usually in a fallopian tube. When detected early, treatment is often with a medication called methotrexate. When methotrexate does not work, surgery is required. A recent clinical trial of ectopic pregnancy treatment (called GEM3) found that adding a drug called gefitinib to methotrexate did not reduce the need for surgery. We have used data from the GEM3 trial, combined with data collected 12 months after the trial finished, to investigate post-methotrexate pregnancy outcomes. We found no difference in pregnancy rates, pregnancy loss rates and recurrent ectopic pregnancy rates between those treated medically only and those who subsequently also needed surgery. The surgical technique used also did not affect pregnancy rates. This research provides reassurance that women with ectopic pregnancies treated medically who need surgery have similar post-treatment pregnancy outcomes to those treated successfully medically.

Low-dose methotrexate-induced renal failure in a patient with ectopic pregnancy: a case report.

BACKGROUND: Methotrexate is an anticancer drug from the antimetabolite class. It is also used in gynecology and obstetrics for the medical treatment of ectopic pregnancies. Low-dose methotrexate-induced adverse toxic effects are rare. We report a case of toxic effect associated with severe renal insufficiency induced by LD-MTX (Low-Dose Methotrexate) for ectopic pregnancy. CASE PRESENTATION: A 46-year-old Chinese woman was in an operation for an ectopic pregnancy of tubal interstitial pregnancy. The embryo villus was so little that we were not sure if it was evacuated, then it was followed with 50 mg methotrexate injection of intramuscular adjacent the uterine horn in the operation. 48 hour later after injection the patient presented with renal failure. The personalized genetic testing showed that MTHFR (677C > T) and ABCB1 (3435T > C) were detected. Gradually, the symptoms improved after calcium leucovorin (CF) rescue, continuous renal replacement therapy (CRRT), promoting blood system regeneration, and multiple supportive treatments. CONCLUSIONS: When toxic effects are suspected, detecting the polymorphisms of an MTHFR gene and monitoring MTX concentration in blood could assist us to formulate individualized and active treatments. The management should be multidisciplinary and as much as possible within an intensive care unit.

Reproductive outcomes of ectopic pregnancy with conservative and surgical treatment: A systematic review and meta-analysis.

BACKGROUND: Ectopic pregnancy (EP), one of the most common gynecological emergencies, is the major cause of maternal death in the first trimester and increases the incidence of infertility and repeat ectopic pregnancy (REP). The aim of this study was to compare the effects of different treatment methods for tubal EP on natural pregnancy outcomes. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Clinical Trials for observational studies on EP (published until October 30,2022 in English) comparing methotrexate (MTX) versus surgery, MTX versus salpingostomy, MTX versus salpingectomy, salpingostomy versus salpingectomy, and MTX versus expectant treatment. Our main endpoints included subsequent natural intrauterine pregnancy (IUP) and REP. We assessed the pooled data using Review Manager software (version 5.3) with a random effects model. RESULTS: Of 1274 identified articles, 20 were eligible and 3530 participants were included in our analysis. There was a significant difference in the odds of subsequent IUP in tubal EP patients who underwent MTX compared with those who were treated with surgery [odds ratios (OR) = 1.52, 95% confidence interval (CI):1.20-1.92]. No significant difference was found in the odds of REP between the 2 groups (OR = 1.12, 95% confidence interval [CI]: 0.84-1.51). There was no significant difference in the odds of subsequent IUP and REP in patients after MTX compared to those after salpingostomy (OR = 1.04,95% CI: 0.79-1.38; OR = 1.10, 95% CI: 0.64-1.90). There was a significant difference in the odds of subsequent IUP in patients after MTX compared with those after salpingectomy (OR = 2.11, 95% CI: 1.52-2.93). No significant difference was found in the odds of REP between the 2 groups (OR = 0.98, 95% CI: 0.57-1.71). There was a significant difference in the odds of subsequent IUP between patients who underwent salpingostomy and those who underwent salpingectomy (OR = 1.61, 95% CI: 1.29-2.01). No significant difference was found in the odds of REP between the 2 groups (OR = 1.21, 95% CI: 0.62-2.37). There was no significant difference in the odds of subsequent IUP and REP in patients after MTX compared with those after expectant treatment (OR = 1.25, 95% CI: 0.64-2.45; OR = 0.69, 95% CI: 0.09-5.55). CONCLUSION: For hemodynamically stable tubal EP patients, MTX has advantages over surgery, particularly salpingectomy, in improving natural pregnancy outcomes. However, MTX is not inferior to salpingostomy and expectant treatment.

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.

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.

Alternative beta-hCG follow-up protocols after single-dose methotrexate therapy for ectopic pregnancy: A retrospective cohort study.

OBJECTIVE: This study assessed the relevance of reductions in beta-hCG levels between days 0 and 4 and between days 0 and 7 after single-dose methotrexate therapy, and the success of the therapy. STUDY DESIGN: A retrospective cohort study of 276 women diagnosed with ectopic pregnancy who received methotrexate as first-line treatment. Demographics, sonographic findings and beta-hCG levels and indexes were compared between women with successful and failed treatment outcomes. RESULTS: The median beta-hCG levels were lower in the success than the failure group on days 0, 4 and 7: 385 (26-9134) vs. 1381 (28-6475), 329 (5-6909) vs. 1680 (32-6496) and 232 (1-4876) vs. 1563 (33-6368), respectively, P < 0.001 for all. The best cut-off for the change in beta-hCG level from day 0 to 4 was a 19% decrease; the sensitivity was 77.0% and specificity 60.0%, positive predictive value (PPV) was 85% CI 95 [78.7.1%-89.9%]. The best cut-off for the change in beta-hCG level from day 0 to 7 was a 10% decrease; the sensitivity was 80.1% and specificity 70.8%, PPV was 90.5% CI 95 [85.1%-94.5%]. CONCLUSIONS: A decrease of 10% in beta-hCG between days 0 and 7 and 19% between days 0 and 4 can be used as a predictor of treatment success in specific cases.

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.

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.