[TruClear™ treatment of caesarean scar pregnancy interrupted after methotrexate injection]. / Résection mécanique hystéroscopique de résidus trophoblastique d'une grossesse sur cicatrice de césarienne après injection de méthotrexate.

BACKGROUND: Cesarean scar pregnancy is a complicated and potentially life-threatening type of ectopic pregnancy. There is no gold standard for its management. The aim is to demonstrate the efficacy and safety of treatment by hysteroscopic tissue removal system after systemic methotrexate injection. METHODS: We report the case of a 27-year-old patient who had previously had a C-section and who presented herself to the emergency room with pelvic pain and metrorrhagia. The human chorionic gonadotrophin (hCG) serum level was positive. The exploration revealed an ectopic pregnancy on the cesarean scar. She benefited of 4 systemic injections of methotrexate. As the hCG became negative, endovaginal ultrasound confirmed the avascular nature of the mass. Surgical resection by mechanical morcellation hysteroscopy (TruClear™) was performed under general anaesthesia, visual control and ultrasound guidance. RESULTS: This procedure was successful. It was an ambulatory procedure and there were neither intra- nor postoperative complications. CONCLUSIONS: To our knowledge, this is the first time in Belgium that a hysteroscopic tissue removal system procedure has been used to treat a caesarean scar pregnancy. This technique seems to be safe for both the patient and the surgeon and could become a new approach for cesarean scar pregnancy management.

CONTEXTE: La grossesse sur cicatrice de césarienne est définie comme la présence d'un sac gestationnel dans une isthmocèle créée par une hystérotomie préalable. Il n'existe pas de gold standard concernant sa prise en charge. L'objectif est de démontrer l'efficacité et la sécurité du traitement par résection mécanique hystéroscopique des tissus après injection systémique de méthotrexate. Méthodes : Nous rapportons le cas d'une patiente de 27 ans ayant déjà eu une césarienne et qui s'est présentée aux urgences avec des douleurs pelviennes et des métrorragies. L'exploration révèle une grossesse sur la cicatrice de césarienne. Elle a bénéficié de 4 injections systémiques de méthotrexate. La résection des résidus trophoblastiques avasculaires a été réalisée par voie hystéroscopique en utilisant l'hystéroscope par action mécanique de type -TruClear™ et ce, sous contrôle échographique concomitant. Résultats : Cette procédure ambulatoire effectuée sous anesthésie générale a été un succès. Il n'y a eu aucune complication per- ou postopératoire. CONCLUSIONS: À notre connaissance, c'est la première fois qu'une résection par action mécanique des résidus trophoblastiques sur cicatrice de césarienne est réalisée en Belgique. Cette technique semble sûre pour la patiente et le chirurgien et pourrait devenir une nouvelle approche pour la prise en charge d'une grossesse sur cicatrice de césarienne.

Successful Management of Cervical and Tubal Stump Double Pregnancy after Assisted Reproductive Technologies Using Multiple High Doses of Methotrexate: A Case Report.

The incidence of ectopic pregnancy (EP) has increased in recent years, owing to causes such as pelvic inflammatory diseases and assisted reproductive technologies (ART). The present study reported a case of a 33-year-old nulliparous woman with a history of previous ectopic pregnancies, who underwent pelvic ultrasound in August 2022, which revealed a double EP including a cervical pregnancy and a tubal stump pregnancy. Despite known risk factors and elevated beta-human chorionic gonadotropin (ß-hCG) levels, a conservative approach, utilizing multiple doses of systemic methotrexate (MTX) injections, was employed to preserve fertility at the Regional Perinatal Center in Aktobe, Kazakhstan. Treatment efficacy was monitored through ß-hCG levels and ultrasound imaging, with successful resolution of both EPs and preservation of reproductive function. The present case highlighted the safety and efficacy of MTX therapy in managing complex EP presentations, emphasizing the necessity of individualized treatment approaches in reproductive medicine, particularly in terms of preserving fertility in patients undergoing ART. Multiple high doses of MTX injections were beneficial for pregnancy with two distinct regions, fetal cardiac activity, and elevated serum ß-hCG level. Further research is required to explore optimal treatment strategies for EP, considering patient-specific factors and treatment goals.

National trends in treatments for ectopic pregnancy in Japan from 2010 to 2020: a retrospective observational study.

BACKGROUND: Ectopic pregnancy (EP) can be treated surgically or nonsurgically. In many countries, methotrexate is frequently used as a first-line medical treatment, and its effect is similar to that of surgery in selected patients. We aimed to investigate national trends in the treatment of EP in Japan. METHODS: We conducted a retrospective observational analysis between 2010 and 2020 using a nationwide claims database that included inpatient data. We identified female inpatients with EP aged 15 to 49 years old. We analysed year-to-year treatment trends for EP, as well as year-to-year trends in methotrexate administration, with a focus on the site of the pregnancy. Patients who received methotrexate were divided into two groups: Those with and those without surgery after methotrexate use. We compared the characteristics of these groups and calculated the methotrexate success rate. RESULTS: We identified 53,653 patients with EP. The proportion of patients undergoing surgery increased from 79% in 2010 to 83% in 2020, whereas the proportion of methotrexate therapy decreased from 8.1% in 2010 to 5.1% in 2020. Regarding methotrexate use for the site of the pregnancy, there was a significant downward trend in methotrexate therapy for tubal pregnancies. Notably, the methotrexate success rate was 84% during the study period. CONCLUSIONS: Surgery showed an increasing tendency over time, whereas methotrexate therapy showed a decreasing tendency for EP treatment in Japan. The efficacy of methotrexate in Japan was comparable to that observed in other countries.

Treatment for ectopic pregnancy includes surgical and non-surgical management. Medical treatment can be as effective as surgery in cases that meet certain criteria. Methotrexate, which is commonly employed as a medical treatment, is widely used in many countries outside Japan. However, reports on methotrexate therapy for ectopic pregnancy in Japan are limited, and the actual status of its use remains unknown. We investigated the treatment trends for ectopic pregnancy in Japan using nationwide inpatient data. The results demonstrated that surgeries increased from 79% in 2010 to 83% in 2020, while methotrexate therapy declined from 8.1% to 5.1%. Methotrexate therapy demonstrated an 84% success rate. Unlike many other countries, surgery became more prevalent while methotrexate therapy decreased for inpatients with ectopic pregnancy in Japan. The success rate of methotrexate in Japan was comparable to that in other countries. Thus, Japanese healthcare providers should consider using methotrexate therapy for appropriate cases and carefully choose the best treatment for each patient after discussing the treatment options with patients.

Comparing the effectiveness of letrozole versus methotrexate for treatment of ectopic pregnancy: A randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of two different regimens of Letrozole, an aromatase inhibitor, in the management of ectopic pregnancy compared to methotrexate. STUDY DESIGN: This randomized controlled trial was conducted on 88 women diagnosed with ectopic pregnancy with a baseline level of serum beta-human chorionic gonadotropin under 3000 mIU/mL between June 30, 2023, and December 30, 2023, at the Department of Obstetrics and Gynecology of the Vali-e-Asr Hospital affiliated with Tehran University of Medical Sciences. Participants were allocated into either methotrexate (n = 43), 5-day course Letrozole (n = 24), or 10-day course Letrozole (n = 21) treatments. The methotrexate group received a single dose of 50 mg/m2 dosage intramuscular methotrexate. The 5-day Letrozole group received a 2.5 mg Letrozole tablet three times daily for 5 days, whereas the 10-day Letrozole group received a 2.5 mg Letrozole tablet twice daily for 10 days. The primary outcome was the treatment response, defined as the achievement of a negative serum beta-human chorionic level without the need for additional methotrexate treatment or surgery. The secondary outcomes were the need for additional methotrexate dose or laparoscopic surgery intervention. The trial protocol was prospectively registered in ClinicalTrials.gov with code NCT05918718. RESULTS: The treatment response rates in methotrexate, 5-day Letrozole, and 10-day Letrozole groups were 76.7 %, 75.0 %, and 90.5 %, respectively, with no significant differences between the groups (P-value = 0.358). A total of 10 (23.3 %) patients from the methotrexate group, 3 (12.5 %) from the 5-day Letrozole group, and 2 (9.5 %) from the 10-day Letrozole group required an additional methotrexate dose, with no significant differences between the groups (P-value = 0.307). Furthermore, only 3 (12.5 %) patients, all from the 5-day Letrozole group, were suspected of tubal rupture and underwent surgery (P-value = 0.016). CONCLUSION: Our findings suggest Letrozole as a safe alternative to methotrexate in treating stable ectopic pregnancies, with a favorable treatment response rate. However, there is still a need for future larger studies to determine the applicability of Letrozole in the EP management. Also, the non-significant higher effectiveness of the 10-day Letrozole regimen than the 5-day Letrozole group underscores the need for future research to determine the optimal Letrozole regimen for the management of ectopic pregnancy.

Comparison of the success rates of a single dose and an additional dose of methotrexate on the 4th day in patients whose ß-hCG values do not fall after a single dose of methotrexate (Day 0-4).

INTRODUCTION: This study's aim is to investigate whether the rise in ß-hCG levels between days 0 and 4 in patients with tubal ectopic pregnancy who have received a single dose of methotrexate has prognostic value in treatment success, and to investigate whether administering a second dose on day 4 enhances treatment success. MATERIAL AND METHODS: Patients diagnosed with ectopic pregnancy and experiencing an increase in ß- hCG levels on day 4 after initiation of methotrexate treatment were included in our study. Patients treated with a single dose Methotrexate (MTX) protocol until December 2019 were retrospectively screened from January 2018 to December 2019. Patients receiving a second dose on day 4 until September 2021 were prospectively enrolled from January 2020 to September 2021. A decrease of over 15 % in the ß-hCG value after the 4th dose was considered as treatment success. RESULTS: Treatment success rates were compared between these two groups. 115 patients with ectopic pregnancy were included in the study. A single dose methotrexate protocol was applied in 67 of the patients (Group 1), while an additional dose methotrexate was applied in 48 (Group 2). The treatment was successful in 40 patients (59.7 %) in Group 1 and in 39 patients (81.3 %) in Group 2. The success rate of the treatment was significantly higher in patients who received an additional dose methotrexate protocol (p = 0.014). DISCUSSION: This study shows that; it is possible to increase success rates by applying an additional MTX dose on the 4th day in cases with an increase in ß-hCG on the 4th day.

Comparison of single- and double-dose methotrexate protocols for treatment of pregnancy of unknown location.

OBJECTIVE: The use of various methotrexate (MTX) protocols for the treatment of ectopic pregnancy is well established. This study aimed to evaluate the efficacy of single- and double-dose MTX protocols for the treatment of pregnancy of unknown location (PUL). STUDY DESIGN: This retrospective study was conducted in the Department of Gynaecological Endocrinology, University Hospital, Krakow, Poland. Haemodynamically stable women with PUL were enrolled between January 2014 and September 2023. Demographics, gestational age and treatment outcomes were compared between women in the single-dose MTX group and women in the double-dose MTX group. The primary outcome was the success rate, measured as the number of women treated without surgical intervention. The secondary outcome was the number of days of MTX needed to achieve an appropriate decrease in beta-human chorionic gonadotrophin (ß-hCG). RESULTS: Two hundred and eleven women (mean age 33 ± 1.8 years) with PUL were enrolled in the study, with an overall success rate of 89.1 %. Single- and double-dose MTX protocols were found to have comparable treatment success rates (93 % and 95 %, respectively). Women with lower initial serum ß-hCG (<2000 mIU/ml) had higher treatment efficacy compared with women with higher initial serum ß-hCG (96.5 % vs 71.4 %), regardless of protocol type. The length of hospital stay for the women treated with the single-dose MTX protocol was 1 day shorter compared with that for the women treated with the double-dose MTX protocol. CONCLUSION: Single- and double-dose MTX protocols have comparable efficacy and safety, and should be equally considered in women with PUL with initial ß-hCG < 2000 mIU/ml.

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.

Pharmacological treatment of ectopic pregnancy: Accuracy, safety and cost-effectiveness of day 1-7 ß-hCG measurements.

OBJECTIVE: The aim of the present study was to compare accuracy, safety and cost-effectiveness of three ß-hCG measurements protocols, applied in managing ectopic pregnancies (EP) with methotrexate (MTX): (1) day 1 to 7 ß-hCG levels, (2) day 1 to 4 ß-hCG levels and (3) day 4 to 7 ß-hCG levels. METHODS: Cost-minimization analysis (CMA) based on a retrospective study of patients treated with single-dose MTX for EP, was evaluated at a single institution between January 2001 to May 2021. Successful MTX treatment was defined as no surgical intervention. We evaluated safety by analyzing cases of day 4 interventions and cases of inconsistency between the different protocols. Predicting accuracy was assessed by the area under the receiver operating characteristic (AUC) curve. RESULTS: A total of 229 patients with single dose MTX treatment were included. Overall, 184 (80.3%) patients were treated successfully with a single dose of MTX. For days 1 and 7 the optimal cutoff point was 7% reduction in ß-hCG levels with sensitivity, specificity and PPV of 76.6% (69.9-82.5, 95% CI), 75.5% (60.5-87.1, 95% CI) and 92.8% (88.4-95.6, 95% CI), respectively. There was no significant difference between the protocols' AUC. None of the patients had any change of management during their day 4 visit in our 20 years of records. The cost for each visit day (day 4 and 7) was calculated with a total cost of 251 USD per patient. CONCLUSION: Patients treated with MTX for EP, measurement of day 1 and day 7 ß-hCG serum levels has a cost minimization advantage and is not inferior to the traditional protocol for predictive accuracy and safety.

Hysteroscopic subchorionic injection of methotrexate followed by laparoscopic excision of the gestational sac for the management of cesarean scar ectopic pregnancy: an innovative dual approach of a challenging pathology.

OBJECTIVE: To describe an effective two-step surgical approach for the management of cesarean scar ectopic pregnancies (CSEPs). CSEPs occur at an estimated frequency of 1 in 1,800 pregnancies, constituting approximately 6% of ectopic pregnancies in women with a history of prior cesarean delivery [1, 2]. Despite numerous recommended therapeutic approaches, the most effective treatment strategy remains uncertain [3]. DESIGN: We present an innovative double-step technique for the management of a patient with a CSEP involving hysteroscopic subchorionic injection of methotrexate (MTX), followed by laparoscopic resection of the residual gestational sac and simultaneous repair of the uterine defect. SETTING: Academic tertiary hospital. PATIENT: A 34-year-old G2P1001 with a history of prior cesarean section presented at 10 weeks of gestation. Ultrasound revealed a gestational sac within the niche of the previous cesarean scar, confirming the diagnosis of a CSEP. The patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, and Scopus, among others), and other applicable sites. INTERVENTION: The initial treatment involved hysteroscopic administration of MTX within the placental intervillous spaces, ensuring precise medication delivery. The administered dose of MTX was 1 mg/kg. Following the normalization of beta-human chorionic gonadotrophin (ß-hCG) levels, laparoscopic resection of the remaining gestational sac and reconstruction of the uterine wall defect were performed. MAIN OUTCOME MEASURES: We have implemented a management strategy focusing on ectopic pregnancy removal and addressing defect revision. The hysteroscopic approach allows for a clear assessment of the ectopic pregnancy and facilitates precise MTX administration, enhancing its effectiveness by increasing drug concentration within the placental intervillous space. Delaying surgical repair until after the ß-hCG levels have decreased reduces the risk of excessive bleeding during the procedure, as lower ß-hCG levels are associated with reduced vascularity at the ectopic site. Subsequent laparoscopic resection allows for complete removal of the remaining products of conception and repair of the defect, preserving the uterus and restoring normal anatomy. Compared to other surgical approaches, our two-step approach enables a more precise evaluation of placental implantation, making it a highly effective surgical method. RESULTS: We successfully managed a CSEP using a double-step technique. This involved hysteroscopic injection of subchorionic MTX, followed by laparoscopic resection of the residual gestational sac. Concurrently, we repaired the uterine defect. Both procedures were performed in an outpatient setting without complications detected during or after treatment. At the follow-up visit, the patient reported good health, and subsequent ultrasound confirmed an empty isthmocele. CONCLUSION: This sequential hysteroscopic and laparoscopic approach represents a definitive and effective minimally invasive surgical option for the treatment of CSEP.

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 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.

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.

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.

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.

Safety profile of methotrexate used off-label in ectopic pregnancy: an active monitoring study based on a Chinese hospital pharmacovigilance system.

OBJECTIVE: Methotrexate (MTX) is characterized as first-line therapy although its indication of ectopic pregnancy is off-label use. We aimed to conduct a retrospective cohort study to investigate the incidence, characteristics of adverse drug reactions (ADRs) of MTX, provide valuable insights for medical workers. METHODS: Basing on China Hospital Pharmacovigilance System (CHPS), a retrospective analysis was performed to evaluate the safety of MTX (n = 672). An active monitoring model was set to detect ADR signals from the hospital information system. Frequency, Common Terminology Criteria for Adverse Events (CTCAE) grade proportion and association of dose exposure with ADRs were presented as outcomes. RESULTS: The total incidence of ADRs was 54.0%. Anaemia (37.6%) was the most frequent ADR, followed by hepatic function abnormal (11.3%), hyperuricemia (6.1%), neutropenia (4.6%), leukopenia (4.0%), and dyslipidaemia (2.5%). For the composition of all ADRs, CTCAE grade one, two and three dominated for 86.3%, 12.1% and 1.6%, respectively. The severity of hepatic function abnormal was more serious in the two-dose exposed group (p = .021), while other types of ADRs had no statistical or clinical differences. Logistic regression analysis showed the incidence of any ADRs (OR 1.87 [1.31-2.64]; p = .001), hepatic function abnormal (OR 2.75 [1.69-4.48]; p < .001), dyslipidaemia (OR 5.15 [1.87-14.13]; p = .001) were significantly higher in the two-dose exposed group. After adjusted, the positive associations were still maintained. CONCLUSIONS: MTX is quite safe in ectopic pregnancy, despite its mild to moderate hematotoxicity, hepatotoxicity and nephrotoxicity. Taking CHPS can present the accurate denominator of the incidence of adverse drug reactions into account, our study advocates that it may have great potential to be used as an active monitoring tool for off-label drug use risk management.

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.

hCG trends after mifepristone and misoprostol for undesired pregnancy of unknown location.

OBJECTIVES: To describe human chorionic gonadotropin (hCG) trends for patients with a pregnancy of unknown location (PUL) presenting for medication abortion by management strategy and outcome. STUDY DESIGN: This retrospective cohort study included patients presenting for medication abortion with a PUL at ≤42 days gestation managed with either (1) immediate mifepristone with serial hCG follow-up (same-day-start) or (2) hCG testing every 48 to 72 hours ± ultrasonography to confirm pregnancy location followed by treatment (delay-for-diagnosis). The primary outcome was percent hCG change over time between presentation and diagnosis, summarized using a multivariate regression model. RESULTS: Of the 55 same-day-start patients, none were treated for ectopic. The eight who eventually required suction curettage had median hCG percent changes (interquartile range) on days 3, 4, and 5 of +57% (-14 to 127; n = 2), +292% (226-353; n = 4), and +392% (n = 1), while the 41 successful medication abortions had declines of -64% (n = 1), -65% (-75 to -27; n = 17), and -77% (-85 to -68; n = 13). Of the 380 delay-for-diagnosis patients, the 30 ectopic pregnancies had day 3, 4, and 5 changes of +38% (-17 to 56; n = 14), +50% (17-71; n = 7), and +115% (87-177; n = 4). None of the ectopic pregnancies declined ≥50% by days 3 to 5. The hCG trend for ectopic pregnancies differed from successful medication abortions (p < 0.01), but not medication abortions with retained intrauterine pregnancies (p = 0.41). CONCLUSIONS: Serum hCG trends can help differentiate ectopic pregnancy from successful medication abortion, but cannot distinguish between ectopic and retained intrauterine pregnancy. IMPLICATIONS: Serial serum hCG testing is effective for confirming successful medication abortion and identifying patients requiring further follow-up among patients undergoing medication abortion for an undesired PUL.

[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.