Treatments for cesarean scar pregnancy: a systematic review and meta-analysis.

OBJECTIVE: To report the outcome of cesarean scar pregnancy (CSP) undergoing treatment. METHODS: MEDLINE, Embase and CINAHL databases were searched. Inclusion criteria were women with CSP undergoing treatment. The primary outcome was successful treatment for CSP, defined as no need for additional medical or surgical strategies. Secondary outcomes were the type of additional treatment (surgical or medical), need for blood transfusion, emergency laparotomy, hysterectomy, post-treatment complications.All these outcomes were explored in women undergoing single and compound treatments for CSP. Furthermore, we performed a separate sub-group analysis only including studies which reported on the outcomes of elective treatments. Random effects meta-analyses were used to analyze the data and results reported as pooled proportions or odd ratio (OR). RESULTS: 176 studies (13431 women with CSP undergoing treatment) were included.Successful treatment after primary intervention was achieved in 86.2% (95% CI 82.3-89.7) of women with CSP undergoing treatment with ultrasound guided suction curettage, 72.4% (95% CI 64.8-79.3) with systemic MTX, 81.6% (95% CI 72.3-89.3) with local MTX, 83.9% (95% CI 66.7-95.6) with interventional radiology, 90.42% (95% CI 82.9-96.0) with hysteroscopy, 96.1% (95% CI (92.3-98.6) with laparoscopy and 92.6 with high intensity focused ultrasound (95% CI 78.2-99.6). Post-treatments complications were reported in 3.5% (95% CI 1.7-6.0) of women treated with systemic MTX, 5.9% (95% CI 0.8-15.1) with local MTX or KCl, 1.2% (95% CI 0.1-3.5) with interventional radiology, 1.4% (95% CI 0.4-2.9) with hysteroscopy, 5.5% (95% CI 0.4-25.7) with high intensity focused ultrasound and in none of the cases treated with ultrasound guided suction curettage.When considering compound treatments, successful resolution of CSP was achieved in 91.9% (95% CI 88.0-95.10) of women treated with interventional radiology followed by curettage, 83.3% (95% CI 68.8-93.8) with systemic MTX and curettage, 79.4% (95% CI 56.3-95.2) with local MTX and curettage, 96.2% (95% CI 92.3-98.7) with curettage followed by single or double balloon insertion in the uterine cavity, 98.3% (95% CI 95.9-99.7) with high intensity focused ultrasound followed by curettage, 91.1% (95% CI 3.4-97.0) with interventional radiology followed by removal of CSP with hysteroscopy, 64.3% (95% CI 13.8-99.2) with interventional radiology and systemic MTX and in 95.5% (95% CI 92.9-97.5) with curettage and hysteroscopy.When considering studies reporting a comparison between different treatments, there was no difference between systemic vs local MTX in the primary outcome. Curettage was associated with a higher chance of achieving a successful treatment. CONCLUSIONS: A multitude of treatments for CSP have been reported in the published literature. All treatments described for CSP are apparently equally effective in treating this condition. The findings from this systematic review highlight the need for adopting a common definition and outcome reporting of CSP to better elucidate its natural history, estimate the magnitude of maternal complication after treatment and design appropriately powered RCT to elucidate the optimal treatment of CSP according to its ultrasound phenotype and gestational age at treatment, in terms of effective resolution of the condition and risk of post-intervention complications.

Outcomes After Early Pregnancy Loss Management With Mifepristone Plus Misoprostol vs Misoprostol Alone.

Importance: Medication management of early pregnancy loss (EPL), or miscarriage, typically involves the administration of misoprostol with or without pretreatment with mifepristone. Combination treatment with mifepristone plus misoprostol is more effective than misoprostol alone but is underutilized in the US. Objective: To describe differences in clinical outcomes after EPL management with mifepristone plus misoprostol vs misoprostol alone using commercial claims data. Design, Setting, and Participants: This retrospective cohort study used national insurance claims data from the IBM MarketScan Research Database. Participants included pregnant people (aged 15-49 years) with private insurance who presented with an initial EPL diagnosis between October 1, 2015, and December 31, 2022. Exposures: The primary exposure was the medication used to manage EPL (ie, mifepristone plus misoprostol or misoprostol alone). Other exposures of interest included demographic characteristics and location of service. Main Outcomes and Measures: The primary outcome was subsequent procedural management (eg, uterine aspiration) after EPL diagnosis and medication management. Other outcomes of interest included return visits, hospitalizations, and complications occurring in the subsequent 6 weeks. Descriptive statistics and bivariate analyses were used, and a multivariable logistic regression model was created to examine factors associated with subsequent procedural management. Results: This study included 31 977 patients (mean [SD] age, 32.7 [5.6] years) with claims for EPL who received medication management. Of these patients, 3.0% received mifepristone plus misoprostol and 97.0% received misoprostol alone. Patients who received misoprostol with pretreatment with mifepristone were less likely to have subsequent uterine aspiration (10.5% vs 14.0%; P = .002), and they were also less likely to have subsequent emergency department (ED) visits for EPL (3.5% vs 7.9%; P < .001). In multivariable analysis, use of mifepristone plus misoprostol was associated with decreased odds of subsequent procedural management (adjusted odds ratio, 0.71 [95% CI, 0.57-0.87]). Conclusions and Relevance: The findings of this study suggest that mifepristone is underutilized for the medication management of EPL, but its use is associated with a lower need for subsequent uterine aspiration and a decrease in the number of subsequent visits to an ED. Increasing access to mifepristone for EPL management may decrease health care utilization and expenditures.

Conservative treatment of cesarean scar pregnancy with the combination of methotrexate and mifepristone: A systematic review.

BACKGROUND: Cesarean scar pregnancy (CSP) has become more frequent as a direct consequence of the increased number of cesarean deliveries and the advances in imaging. Although some cases are characterized by spontaneous resolution, unrecognized or mishandled CSP has the potential to cause both fetal and maternal morbidity and mortality. However, due to its infrequency, there is no agreement on the best management. OBJECTIVE: The purpose of this study was to evaluate the safety, the risks and effectiveness of medical therapy with methotrexate and mifepristone to better understand its role in CSP therapy. DESIGN: This study is a systematic review. DATA SOURCES AND METHODS: The electronic databases PubMed, Medline, and Scopus were comprehensively searched until December 2023. Medical Subject Headings terms (Cesarean scar pregnancy) AND (Methotrexate) AND (Mifepristone) AND (Medical Therapy) were used to identify the relevant records. Due to the rarity of this pathology, the studies included are all case reports or case series. The methodological quality of the included studies was assessed using the JBI Critical Appraisal Checklist for case reports. RESULTS: We included in our review a total of seven cases reported in five manuscripts at the end of the screening process. Our review suggests that this type of combination treatment can be considered. The success rate is 71.4%. Treatment seems to be most effective when beta human chorionic gonadotropin (B-hCG) is below 5,000 mUi/ml and when the gestational sac is less than 20 mm. The absence of fetal heartbeat seems to be a positive prognostic factor for a positive outcome. CONCLUSION: Methotrexate and mifepristone administration can be considered as an alternative first-line effective treatment, especially in case of pregnancy with B-hCG <5,000 mUi/ml and when the gestational sac is less than 20 mm. It is important to individualize the management and treatment according to the clinical condition, the patient's age, number of previous cesarean deliveries, willingness to have other children, and the physicians' experience.

Unrecognized Cesarean Scar Pregnancy has the potential to cause both fetal and maternal morbidity and mortality. Methotrexate (MTX) and Mifepristone administration can be considered as an alternative first-line effective treatment especially in case of pregnancy with a low BHCG and when the gestational sac is less than 20 mmCesarean scar pregnancy (CSP) has become more frequent as a direct consequence of the increased number of Cesarean deliveries and the advances in imaging. Unrecognized CSP has the potential to cause both fetal and maternal morbidity and mortality. However, there is no agreement on the best management. The purpose of this study was to evaluate the safety, the risks, and effectiveness of medical therapy with methotrexate and mifepristone. The electronic databases PubMed, Web of Science, and Scopus were comprehensively searched until December 2023. We included in our review a total of seven cases reported in five5 manuscripts at the end of the screening process. Our review suggests that this type of combination treatment can be considered. The success rate is 71.4%. Treatment seems to be most effective when B-hCG is below 5000 mUi/ml and when the gestational sac is less than 20 mm. methotrexate (MTX) and mifepristone administration can be considered as an alternative first-line effective treatment.

Multimodal management of ectopic hepatic pregnancy: a systematic review of the literature.

PURPOSE: Ectopic pregnancies with implantation in the upper abdomen are exceptionally rare. Here we provide a systematic review of hepatic ectopic pregnancies and the corresponding management strategies. Furthermore, this report details a case of ectopic hepatic pregnancy, successfully treated with primary methotrexate (MTX) followed by a two-staged robotic-assisted resection. METHODS: Two independent investigators performed a systematic review using the online search engine PubMed and MEDLINE database. The search utilized the following terms: 'Hepatic Ectopic Pregnancy,' 'Hepatic Extrauterine Pregnancy,' 'Hepatic Abdominal Pregnancy,' and 'Ectopic Liver Pregnancy.' Cross-referencing was employed to identify possible additional publications. FINDINGS: Forty-seven case reports on hepatic pregnancies were identified. Of these, 40 provided manuscripts in the English language. Most patients with hepatic pregnancy presented with mild to moderate abdominal pain, while only a minority exhibited signs of hemodynamically relevant intraperitoneal hemorrhage. Most cases were managed through open surgical removal, although in recent years, there has been an increase in laparoscopically managed cases. Conservative approaches using methotrexate are seldom employed. CONCLUSION: Hepatic pregnancies present a rare and challenging clinical scenario. Until now, these cases have usually been treated primarily with open explorative surgery. As reported in this case, primary conservative treatment approaches with MTX before surgery hold promise as a strategy to reduce surgery-related bleeding and morbidity, particularly for asymptomatic or oligosymptomatic patients.

Comparison of 2-year reproductive outcomes of tubal ectopic pregnancies treated with surgery, methotrexate or expectant management.

INTRODUCTION: To compare the 2-year reproductive outcomes of tubal ectopic pregnancies (EP) treated with surgery, methotrexate (MTX) or expectant management. MATERIALS AND METHODS: This case-control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. 985 of 1156 patients, who were managed between January 2015 and December 2019 for a tubal EP, tried to conceive in 2 years after treatment: 366 patients underwent surgical treatment; 549 patients were treated with MTX, and 70 patients had expectant management. Clinical data and fertility outcomes were retrieved by medical and hospital records. We compared the three groups based on the 2-year reproductive outcomes of three treatment modalities of tubal EP. RESULTS: There was a significant difference in the frequency of no pregnancy in patients who underwent surgery compared to patients who received expectant management and MTX therapy (p < 0.001). The frequency of no pregnancy was higher in patients who underwent surgery. There was no significant difference between expectant management and MTX therapy (p = 0.411). In the reproductive outcomes of patients who underwent surgery, the incidence of viable pregnancies was statistically lower than in the group treated with expectant management and MTX therapy (p = 0.003). CONCLUSIONS: Patients with an EP often have a future desire to have children, the treatment options are also important. The earlier the diagnosis is made, the more likely it is that expectant management or MTX treatment will be considered. With these two treatment methods, the likelihood of having a child in the future is higher than with surgical treatment.

Medical treatment of miscarriage using misoprostol-a retrospective study.

PURPOSE: The treatment of early miscarriage with medication is effective and low in side effects. Nevertheless, no uniform dosage regimen has yet been established, nor has it been possible to determine whether previous pregnancies and births with their respective modes of delivery play a role in the effectiveness of Misoprostol. This study aimed to find predictive parameters for successful treatment with Misoprostol in early miscarriage. METHODS: In a retrospective study at the Otto von Guericke University Women's Hospital, records of patients with early miscarriage and medical treatment using Misoprostol from 2018 to 2021 were reviewed for this purpose. The need for a curettage subsequent to treatment was scored as a parameter of failure. The data were analyzed using Statistical Package for the Social Science Version 28.0. The significance level was set to 0.050. RESULTS: We found that successful therapy with misoprostol was seen in 86% (n = 114). 14% (n = 20) of the patients had curettage after taking Misoprostol as advised. Out of 134 women, 16% (n = 21) reported mild side effects, with nausea as the leading one (9.2% (n = 12)). Significance was found comparing the measurement of double endometrial stripe thickness after the second cycle of Misoprostol in women with and without curettage after medical treatment (exact value two-sided 0.035 at p < 0.05). A cutoff value at 8.8 mm was calculated using ROC Analysis. CONCLUSIONS: Our results indicate that the treatment of early miscarriage in the first trimester with Misoprostol is effective and has few side effects. The measurement of the endometrial stripe thickness after the second cycle of Misoprostol via transvaginal ultrasound could present a predictive marker during therapy.

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.

[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.

The Success of Mifepristone and Misoprostol in the Management of Early Pregnancy Loss at a Community Hospital: A Prospective Study.

OBJECTIVES: This prospective single-arm study was conducted to understand the expulsion rate of the gestational sac in the management of early pregnancy loss (EPL). METHODS: We recruited 441 participants; 188 met the eligibility criteria. Participants were 18 years of age and older who experienced a confirmed EPL (<12 weeks gestational age) defined by an intrauterine pregnancy with a non-viable embryonic or anembryonic gestational sac with no fetal heart activity. Participants were given 200 mg of mifepristone pre-treatment orally followed by 2 doses of misoprostol 800 µg vaginally after 24 and 48 hours. Participants were seen in follow-up on day 14 to confirm the absence of a gestational sac, classified as treatment success. For failed treatment (defined by retained gestational sac), we offered expectant management or a third dose of misoprostol and/or dilatation and curettage. We followed all participants for 30 days. We collected data on overtreatment for retained products of conception and hospital admissions for adverse events. RESULTS: Overall, 181 participants followed the protocol and 169 (93.3%) participants had a complete expulsion of the gestational sac by the second visit (day 14). Twelve (6.6%) failed the treatment and 1 had an adverse event of heavy vaginal bleeding requiring dilatation and curettage. Despite the expulsion of the gestational sac, 29 cases (17.1%) at subsequent follow-up were diagnosed as retained products of conception based on ultrasound assessment of thickened endometrium. CONCLUSIONS: Pretreatment with mifepristone followed by 2 doses of misoprostol with a 14-day follow-up resulted in a high expulsion rate and is a safe management option for EPL.

Direct Visualization of a Cesarean Scar Ectopic Pregnancy After Medical Management.

BACKGROUND Cesarean scar ectopic pregnancy is a rare type of ectopic pregnancy that can result in severe maternal morbidity and mortality. Medical, surgical, and minimally invasive therapies alone or in combination have been described in the literature, but the optimal treatment modality of cesarean scar ectopic pregnancies is unknown. Limited information exists on the course of cesarean scar ectopic pregnancy following treatment with cytotoxic agents. CASE REPORT We present a case of a woman with a history of multiple cesarean births that was provided with medical abortion for an unintended pregnancy. However, upon follow-up, the patient was found to have a cesarean scar ectopic pregnancy. Following the diagnosis, she was treated by multi-dose systemic methotrexate-leucovorin and with ultrasound-guided intra-gestational sac injection of potassium chloride. After resolution of beta human gonadotropin levels, ultrasound follow-up revealed persistence of residual tissue in the cesarean scar. The patient elected for resection of the residual tissue with operative hysteroscopy. We report a novel hysteroscopic finding after medical treatment of a cesarean scar ectopic pregnancy with intra-gestational sac injection of potassium chloride. CONCLUSIONS Direct visualization of the intra-abdominal cavity and intra-uterine cavity showed that combined medical management with systemic methotrexate and local potassium chloride injection is an effective treatment modality for live cesarean scar ectopic pregnancies, with minimal anatomical harm. Hysteroscopic resection offers a safe and effective approach for removal of persistence of residual tissue.

Systemic methotrexate (MTX) in early pregnancy: a retrospective study of a tertiary maternity hospital.

BACKGROUND: Methotrexate (MTX) is used in clinical practice as a medical treatment option in patients with early pregnancy complications like ectopic pregnancy. AIMS: To review systemic MTX therapy use in the first trimester of pregnancy in our hospital and to examine subsequent clinical outcomes. METHODS: Retrospective review of all women treated with systemic MTX in early pregnancy identified from electronic prescription records from 1 January 2018 to 31 December 2020 at Cork University Maternity Hospital, Ireland. Relevant data was transcribed from electronic health records. RESULTS: Indications for treatment were tubal ectopic pregnancy (70%, n = 51), persistent pregnancy of unknown location (22%, n = 16) and caesarean scar pregnancy (7%, n = 5). Treatment was successful in 88% (n = 44) of tubal ectopic pregnancies with 73% (n = 37) and 14% (n = 7) of women receiving a single dose and repeated doses, respectively. Only 8% (n = 4) of tubal ectopic pregnancies required emergency surgery for subsequent tubal rupture. In 93% (n = 15) of cases of persistent pregnancy of unknown location, treatment was successful with one patient requiring uterine evacuation. Women with caesarean scar pregnancy were treated with combined MTX and uterine evacuation without complication. CONCLUSIONS: The efficacy of medical treatment with systemic MTX for confirmed tubal ectopic pregnancy in our hospital is in line with national and international standards. Careful consideration should be given to treating caesarean scar pregnancy and persistent pregnancy of unknown location with systemic MTX. Systemic MTX use guided by clinicians specialised in early pregnancy complications and safe medication practices may improve treatment success and reduce adverse events.

A 20 year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital - a retrospective review.

BACKGROUND: Non-tubal ectopic pregnancies account for < 10% of all ectopic pregnancies. Due to its rarity and wide variation in clinical practice, there is no guideline or consensus for its management. We reported our 20-year experience in the management of non-tubal ectopic pregnancies in a tertiary hospital. METHODS: This is a retrospective review of all women admitted for non-tubal ectopic pregnancies from January 2003 to December 2022 in a tertiary hospital. Women with non-tubal ectopic pregnancies diagnosed by ultrasound or operation were included for analysis. RESULTS: Within the study period, 180 women were diagnosed to have non-tubal ectopic pregnancies at a mean gestation of 6.8 weeks. 16.7% (30/180) were conceived via assisted reproduction. Medical treatment was the first-line management option for 81 women, of which 75 (92.1%) women received intralesional methotrexate administered under transvaginal ultrasound guidance. The success rate of intralesional methotrexate ranges from 76.5% to 92.3%. Intralesional methotrexate was successful even in cases with a positive fetal pulsation or with high human chorionic gonadotrophin levels up to 252605U/L. Twenty seven women were managed expectantly and 40 underwent surgery. Nine (11.1%), two (6.1%), and one (2.3%) women required surgery due to massive or recurrent bleeding following medical, expectant, or surgical treatment. Hysterotomy and uterine artery embolization were necessary to control bleeding in one Caesarean scar and one cervical pregnancy. CONCLUSIONS: Intralesional methotrexate is more effective than systemic methotrexate and should be considered as first line medical treatment for non-tubal ectopic pregnancies. It has a high success rate in the management of unruptured non-tubal ectopic pregnancies even in the presence of fetal pulsations or high human chorionic gonadotrophin levels, but patients may require a prolonged period of monitoring. Close surveillance and readily available surgery were required due to the risk of heavy post-procedural intra-abdominal bleeding.

Systematic evaluation of the efficacy of treatments for cesarean scar pregnancy.

STUDY OBJECTIVE: Cesarean scar pregnancy (CSP) is a type of ectopic pregnancy associated with severe complications, including significant hemorrhage, the potential need for hysterectomy, and life-threatening risks. Currently, two classification methods exist for CSP: Vial (type Ia and IIa) and Chinese Expert's Consensus (type Ib, type IIb, and type IIIb). However, these methods have limitations in guiding the selection of appropriate treatment plans for CSP. The purpose of this study was to systematically evaluate the effectiveness of various treatments for CSP within our clinic. METHOD: Our study included 906 patients with CSP from January 2013 to December 2018. The chi-squared test and logistic analysis were used to compare the clinical characteristics. The median and interquartile range (IQR) was calculated. We also analyzed whether preoperative application of methotrexate (MTX) could improve surgical outcomes and the relevant characteristics of misdiagnosed CSP patients. RESULTS: There was a significant difference in gestational age, gestational sac diameter, gestational sac width, gestational sac area, remnant myometrial thickness, vaginal bleeding and preoperative hemoglobin levels (p < 0.001) but not in the incidence of residual tissue (p = 0.053). The other factors (intraoperative blood loss, hemoglobin decline, first hemoglobin after operation, total hospital stay, hospital stay after operation, transfusion and duration of catheter drain) were significantly different (p < 0.001). For type Ia and type Ib CSP, 39.3% and 40.2% of patients were treated with dilatation and curettage (D&E) under ultrasound, respectively. For type IIa and type IIIb CSP, 29.9% and 62.7% of patients were treated with laparotomy, respectively. There were no differences in surgical methods, residual tissue and reoperation between the MTX and non-MTX groups (p = 0.20), but liver damage, hospital stay and pain perception were more remarkable in the MTX group. It is noteworthy that 14% of the patients were misdiagnosed with an intrauterine pregnancy. The incidence of misdiagnosis in type IIa CSP patients was higher than that in type Ia CSP patients (p < 0.001). CONCLUSION: For type I CSP patients, D&E under ultrasound or D&E under hysteroscopy should be recommended. For type IIIb CSP patients, operative resection should be used. It is currently difficult to choose the appropriate treatment methods for type IIa or type IIb CSP patients.

Efficacy of letrozole for the treatment of tubal ectopic pregnancy: A meta-analysis.

BACKGROUND: Tubal ectopic pregnancy (EP) is a life-threatening condition, especially if undiagnosed or misdiagnosed, tipically in low income countries and/or where women have limited access to health care. The current management protocol of tubal EP consists of either surgical management, or medical management with methotrexate. Recent studies, while few, have suggested that letrozole, an aromatase inhibitor, may play a role in the medical treatment of tubal EP. OBJECTIVES: To evaluate the effectiveness of letrozole alone in the medical treatment of tubal EP. SEARCH STRATEGY: Electronic databases were searched until 31 December 2023. SELECTION CRITERIA: Retrospective or prospective studies reporting the treatment of tubal EP with letrozole alone were considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: Pooled results were expressed as OR with 95 %CI. Heterogeneity was assessed using Higgins I2. Subgroup analysis was performed to compare outcomes according to time after intervention. Subgroup differences were checked through χ2 test. RESULTS: A total of 152 patients were included. Seventy-nine patients (51.97 %) were treated with letrozole, 39 patients (16.54 %) with methotrexate, and 34 patients (31.49 %) underwent surgical treatment. Pooled data analysis supports the consistency of the effect of letrozole in reducing ß-hCG over time at a comparable rate among studies, and that treatment with letrozole is superior to surgery and has the same efficacy as methotrexate. However, all the included studies were judged at high risk of bias in terms of study design, sample representativeness, and sampling technique. Furthermore, short and long term side effects were not reported in any of the included studies. CONCLUSIONS: Letrozole is a promising alternative to methotrexate and surgical therapy in the treatment of tubal EP. Although this meta-analysis suggests efficacy and low hazard of the drug and encourages its application, the data available today remain extremely sparse, which weakens any claims that can be made, and is not sufficient to assert that letrozole is safe and effective in the treatment of EPs. There is an absolute need for randomized studies with accurate patient selection, fixed doses, large sample sizes, and reporting of short- and long-term side effects to refute or confirm this assumption.

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.

The predictors of successful methotrexate treatment of tubal ectopic pregnancy.

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

Ectopic pregnancy is a pregnancy that occurs outside the uterus. It needs to be identified and treated quickly to prevent serious health complications. Ectopic pregnancies can be treated surgically or medically using a drug called methotrexate. Medical treatment of ectopic pregnancy is not always successful. Identifying the factors that predict the failure of medical treatment helps patients and doctors to choose more accurately between surgical and medical treatment options.A total of 292 women who received methotrexate for ectopic pregnancy and the factors that influence the outcomes of treatment were examined, 39 patients had treatment failure and required surgery. Older age, higher initial levels of ß-human chorionic gonadotropin (ß-hCG) hormone, the presence of pelvic pain, and foetal cardiac activity had increased risk of treatment failure. In the future, research could consider the relationship between the size of the ectopic pregnancy and the treatment outcomes and refine the ß-hCG level cut-off for better treatment effects.

Efficacy and safety of isosorbide mononitrate plus misoprostol compared to misoprostol alone in the management of the first and second trimester abortion: a systematic review and meta-analysis.

BACKGROUND: However, misoprostol is often used to terminate a pregnancy, but it can also cause side effects. Isosorbide mononitrate (ISMN) can help the cervix mature by increasing the production of prostaglandin E2 and vasodilation. Considering that the results of studies in this field are contradictory, it is the purpose of this study to evaluate the efficacy and safety of vaginal ISMN plus misoprostol compared to misoprostol alone in the management of first- and second-trimester abortions. METHOD: The search process was conducted for MEDLINE through the PubMed interface, Scopus, Web-of-Science, Science Direct, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform until November 10, 2023. Our assessment of bias was based on version 2 of the risk-of-bias tool (RoB2) for randomized trials and our level of evidence quality was determined by GRADE. Meta-analysis of all data was carried out using Review Manager (RevMan) version 5.1. RESULT: Seven randomized clinical trials were included in the systematic review and three in the meta-analysis, with mixed quality. The results of the meta-analysis revealed that in the second-trimester abortion, the inclusion of ISMN in conjunction with vaginal misoprostol results in a noteworthy reduction in the induction abortion interval, specifically by 4.21 h (95% CI: -7.45 to -0.97, P = 0.01). The addition of vaginal ISMN to misoprostol, compared to vaginal misoprostol alone, increased the odds of a completed abortion by 3.76 times. (95% CI: 1.08 to 13.15, P = 0.04). CONCLUSION: The findings of this study can offer valuable insights aimed at enhancing counseling and support for non-surgical methods of medication abortion within professional settings. Moreover, it improves the effectiveness of clinical treatment and reduces the occurrence of unnecessary surgical interventions in the abortion management protocol.

The effects of conservative and surgical approaches in tubal ectopic pregnancy on fertility.

BACKGROUND: Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to its effectiveness, the main concern is to limit the risk of relapse and preserve fertility. OBJECTIVES: Determine the impact of medical or surgical treatment for ectopic pregnancy on future fertility. DESIGN: Retrospective. SETTING: Department of obstrtrics and gynecolgy at Ankara Etlik Zübeyde Hanim Women's Health Training and Research Hospital, Ankara, Turkey. PATIENTS AND METHODS: Patients who were treated for ectopic pregnancy between June 2016 and November 2019 were allocated into two groups. Expectant approach or medical treatment by methotrexate constituted the conservative treatment group while salpingectomy by laparoscopy indicated the surgical treatment group. MAIN OUTCOME MEASURES: Fertility rates within two years following treatment were evaluated according to treatment options. SAMPLE SIZE: 202 patients. RESULTS: Of the 202 patients, 128 had medical treatment and 74 patients had surgical treatment for ectopic pregnancy. Of 272 diagnosed with ectopic pregnancy, 70 were excluded for various reasons. Parity and unemployment rate was significantly higher in the surgical treatment (P=.006 and P=.12, respectively). Moreover, ectopic mass size and serum ß-hCG levels were significantly higher in the surgical treatment group (P<.001 and P<.001, respectively). There were no significant differences between the conservative and surgical treatment groups in time to pregnancy (17.0 months vs 19.0 months, P=.255). Similarly, there was no significant difference between the conservative and surgical treatment groups with respect to history of infertility (P=.12). There were no significant differences between the conservative and surgical treatment groups in terms of live birth (51.6% vs 44.6%) and ectopic pregnancy (2.3% vs 1.4%) (P=.72 for both). There was no significant difference between the conservative and surgical treatment groups with respect to infertility rate (35.9% vs 41.9%, P=.72) and admittance to the IVF program (3.9% vs 6.8%, P=.39) following ectopic pregnancy treatment. CONCLUSIONS: Reproductive outcomes did not differ significantly in women undergoing expectant management, medical treatment, and surgery for ectopic pregnancy. This finding suggests that clinicians should not hesitate to act in favor of surgical treatment for ectopic pregnancy even if there were concerns for future fertility. LIMITATIONS: Retrospective study.

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.

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.