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.

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.

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.

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.

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.

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.

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.

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 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.

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.

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

Introduction: Ectopic pregnancies are a significant cause of morbidity and mortality in the first trimester of pregnancy. Hospital protocols requiring a specific beta-human chorionic gonadotropin (ß-hCG) level to qualify for diagnostic testing (pelvic ultrasound) can delay diagnosis and treatment. In this study we sought to determine the relationship between ß-hCG level and the size of ectopic pregnancy with associated outcomes. Methods: We performed a retrospective case review of patients diagnosed with ectopic pregnancy in an urban, academic emergency department specializing in obstetrical care, from January 1, 2015-December 31, 2017. Variables extracted included presentation, treatment, adverse outcomes, and rates of rupture. Results: We identified 519 unique ectopic pregnancies. Of those ectopic pregnancies, 22.9% presented with evidence of rupture on ultrasound, and 14.4% showed evidence of hemodynamic instability (pulse >100 beats per minute; systolic blood pressure <90 millimeters of mercury; or evidence of significant blood loss) on presentation. Medical management outcomes were as follows: of 177 patients who received single-dose methotrexate, 14.7% failed medical management and required surgical intervention; of 46 who received multi-dose methotrexate, 36.9% failed medical management and required surgical intervention. Ultimately, 55.7% of patients required operative management of their ectopic pregnancy. Mean ß-hCG level at initial presentation was 7,096 milli-international units per milliliter (mIU/mL) (SD 88,872 mIU/mL) with a median of 1,289 mIU/mL; 50.4% of ectopic pregnancies presented with ß-hCG levels less than the standard discriminatory zone of 1,500 mIU/mL. Additionally, 44% of the patients who presented with evidence of rupture had ß-hCG levels less than 1,500 mIU/mL. Comparison of size of ectopic pregnancy (based on maximum dimension in millimeters) to ß-hCG levels revealed a very weak correlation (r = 0.144, P < .001), and detection of ectopic pregnancies by ultrasound was independent of ß-hCG levels. Conclusion: Levels of ß-hCG do not correlate with the presence or size of an ectopic pregnancy, indicating need for diagnostic imaging regardless of ß-hCG level in patients with clinical suspicion for ectopic pregnancy. Almost one-sixth of patients presented with evidence of hemodynamic instability, and approximately one quarter of patients presented with evidence of rupture requiring emergent operative management. Ultimately, more than half of patients required an operative procedure to definitively manage their ectopic pregnancy.

The MISOPRED score: Development and validation of a clinical scoring system to predict the effectiveness of Misoprostol treatment for early pregnancy loss.

BACKGROUND: Misoprostol treatment for early pregnancy loss has varied success demonstrated in previous studies. Incorporating predictors in a single clinical scoring system would be highly beneficial in clinical practice. OBJECTIVE: To develop and evaluate the accuracy of a scoring system to predict misoprostol treatment outcomes for managing early pregnancy loss. STUDY DESIGN: Retrospective cohort and validation study. METHODS: Patients discharged from the gynecologic emergency department from 2013 to 2016, diagnosed with early pregnancy loss, who were treated with 800 mcg misoprostol, administrated vaginally were included. All were sonographically reevaluated within 48-72 hours. Patients in whom the gestational sac was not expelled or with endometrial lining >30 mm were offered a repeat dose and returned for reevaluation after seven days. A successful response was defined as complete expulsion. Clinical data were reviewed to identify predictors for successful responses. The scoring system was then retrospectively evaluated on a second cohort to evaluate its accuracy. Multivariate logistic regression was performed to identify factors most predictive of treatment response. RESULTS: The development cohort included 126 patients. Six factors were found to be most predictive of misoprostol treatment effectiveness: nulliparity, prior complete spontaneous abortion, gestational age, vaginal bleeding, abdominal pain, and mean sac diameter, yielding a score of 0-8 (the MISOPRED score), where 8 represents the highest-likelihood of success. The score was validated retrospectively with 119 participants. Successful response in the group with the lowest likelihood score (score 0-3) was 9%, compared with 82% in the highest likelihood score group (score 7-8). Using the MISOPRED score, approximately 15% of patients previously planned to receive misoprostol treatment can be referred for surgical management. CONCLUSIONS: MISOPRED score can be utilized as an adjunct tool for clinical decision-making in cases of Early pregnancy loss. To our knowledge, this is the first scoring system suggested to predict the success rate in these cases.

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.

How Effective Is Misoprostol Alone for Medication Abortion?

AbstractWith recent severe restrictions to abortion accessibility in the United States and a pending Supreme Court case challenging the Food and Drug Administration's approval of mifepristone, evidence-based strategies to protect and expand access to abortion care are needed. Two safe and effective regimens for medication abortion are widely used globally - misoprostol-only and misoprostol in combination with mifepristone. However, misoprostol-only regimens are rarely used in the United States. In 2023, the National Abortion Federation and the Society of Family Planning updated their recommended protocol for misoprostol-only for medication abortion to 800 µg of misoprostol administered buccally, sublingually, or vaginally every 3 hours for three or more doses. To characterize the data supporting this specific regimen, this article reviews the relevant literature to address the question of how effective misoprostol-only is for medication abortion. The authors conclude that the updated misoprostol regimen is highly effective and a potential strategy for expanding access to abortion.

Treatment Outcomes of Cesarean Scar Pregnancy Under a Novel Classification System: A Retrospective Cohort Study.

OBJECTIVES: To determine whether the new classification system published by Jordans et al for cesarean scar pregnancy (CSP) can guide management and treatment outcomes. METHODS: A retrospective study of women diagnosed with CSP from October 2010 to December 2022 in a single tertiary center was performed. Sonographic records of these women were classified into three types according to the classification published by Jordans et al. Treatment outcomes were compared across each type of CSP. RESULTS: The study included a total of 84 women, where 60 (71.4%), 17 (20.2%), and 7 (8.3%) of them were categorized into Type 1, 2, and 3 CSP, respectively. A total of 47 (55.9%) women were managed with methotrexate, 22 (26.2%) underwent surgical management of the CSP without removal of the Cesarean section (CS) niche, and 11 (13.1%) underwent surgery to remove the CSP and the CS niche. Overall treatment success rates for medical management and surgical management were 70 and 97%, respectively. Four women were managed expectantly and continued their pregnancies, among which three carried beyond 34 weeks and had good neonatal outcomes. CONCLUSIONS: The classification as published by Jordans et al is easily replicable and readily implemented clinically. Our findings show that a higher proportion of Type 1 and Type 2 CSP were treated successfully by a less invasive medical approach with a high success rate, whereas most Type 3 CSP required surgical resection to successfully remove the CSP and the CS niche. Prospective studies are required to confirm these findings and further validate the clinical utility of this nomenclature system.

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.

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.

The Safety and Efficacy of a "No Touch" Abortion Program Implemented in the Greater Toronto Area During the COVID-19 Pandemic.

OBJECTIVES: To evaluate the safety and efficacy of first-trimester "No Touch" medication abortion programs at 2 clinics in Toronto, Ontario during their early implementation in response to the COVID-19 pandemic. METHODS: This retrospective study included all patients who underwent virtual consultation for mifepristone-misoprostol medication abortion between April 2020-August 2022 at 2 reproductive health clinics. In response to the pandemic, "No Touch" abortion protocols have been developed that align with the Canadian Protocol for the Provision of Medical Abortion via Telemedicine. Records were reviewed for demographic information, clinical course, investigations required, confirmation of complete abortion and adverse events. The primary outcome was complete medication abortion, defined as expulsion of the pregnancy without requiring uterine aspiration. RESULTS: A total of 277 patients had abortions initiated in the "No Touch" or "Low Touch" care pathways and had sufficient follow-up to determine outcomes. Of these patients, 92.8% (95% CI 89.7%-95.8%) had a complete medication abortion (n = 257) and 76.1% (n = 159) remained "No Touch" throughout their care. Investigations were performed for 102 participants before or after their abortion, classifying them as "Low Touch". Nineteen patients (6.9%) underwent uterine aspiration. The rate of adverse events was low, with 1 case of a missed ectopic pregnancy and 1 patient requiring hospitalization for endometritis. CONCLUSIONS: "No Touch" provision of mifepristone-misoprostol medication abortion care was safe and effective with outcomes comparable to previous studies. These results provide evidence for the efficacy and safety of a "No Touch" approach in the Canadian context, which has the potential to reduce barriers to accessing abortion care.

Readmission following methotrexate treatment for tubal pregnancy.

OBJECTIVE: To identify risk factors for readmission following methotrexate treatment for tubal pregnancy. METHODS: A retrospective study undertaken in two tertiary medical centers, including all individuals with medically treated tubal pregnancy (N = 511), between December 2009 and June 2021. Individuals with and without readmission following methotrexate treatment were compared. The primary outcome was the readmission rate. Secondary outcomes included the rate of post-discharge gynecological emergency department visits, tubal rupture rate, and the eventual need for surgical treatment. RESULTS: Readmission following methotrexate treatment occurred in 224/511 patients (43.8%). Most readmissions were due to abdominal pain or suspicion of treatment failure. Readmitted individuals were more likely to have a history of pelvic inflammatory disease and pretreatment serum human chorionic gonadotropin (hCG) >2000 mIU/mL. Both factors remained significantly associated with higher readmission rates in a logistic regression analysis (adjusted odds ratio [OR] 6.28, 95% confidence interval [CI] 1.30-30.45, and adjusted OR 2.73, 95% CI 1.83-4.07, respectively) after adjustment for age, endometriosis, tubal pathology, abdominal pain, and presence of yolk sac or embryo at diagnosis. A dose-dependent association was observed between pretreatment serum hCG levels and readmission rate (P < 0.001). Pretreatment hCG levels were also associated with tubal rupture and the eventual need for surgical treatment (P < 0.001 for both). A prediction model using hCG was not sufficiently accurate to predict readmission risk. CONCLUSION: Readmission following methotrexate treatment for tubal pregnancy was independently associated with previous pelvic inflammatory disease and pretreatment serum hCG levels. The latter was also associated with surgical intervention rate.