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.

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

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

Management of non-tubal ectopic pregnancies analysis of a large tertiary center case series.

PURPOSE: Ectopic pregnancies include cesarean scar (CSP), cornual and cervical pregnancies. Various treatment modalities have been- described, but no standardized procedure has been defined so far. The aim of our analysis was to evaluate the diagnostics and treatment at the Department of Obstetrics and Gynecology, LMU University Hospital, Munich. METHODS: In this retrospective, single-center analysis, 24 patients treated between 2015 and 2020 were analyzed. After verification of the diagnosis by imaging and HCG-analysis, the treatment was individually determined: therapy with methotrexate (MTX) locally with or without simultaneous systemic treatment, surgical treatment via curettage, excision with uterine reconstruction even hemi hysterectomy. RESULTS: Ten patients presented with CSP, six with cervical and eight with cornual pregnancies. Median age was 34.6 years. CSP was treated with local MTX in six cases; five required additional treatment with systemic MTX or curettage. Primary curettage or surgery was performed in four cases. In cervical pregnancies the primary therapy with local MTX injection and systemic treatment was performed in 50%. One patient was treated with MTX and insertion of a Bakri balloon. Trachelectomy was required in one case. 50% of cornual pregnancies were treated with MTX locally and intramuscularly and 50% received surgery. CONCLUSION: Treatment strategies were based on the patient's individual risk parameters. The results of this study show, that simultaneous treatment with local and systemic MTX had good outcomes and could avoid surgeries.

Expectant management of tubal pregnancies with human chorionic gonadotropin up to 2000 mIU/mL.

OBJECTIVE: To describe outcomes of expectant management (EM) versus methotrexate (MTX) treatment in tubal pregnancies with pretreatment human chorionic gonadotropin (hCG) less than 2000 mIU/mL. METHODS: This retrospective cohort from two tertiary hospitals included women with confirmed tubal pregnancies and pretreatment hCG <2000 mIU/mL. Exclusion criteria were unrecorded pregnancy site, unconfirmed diagnosis, and surgical treatment upon diagnosis. The primary outcome was eventual rate of surgical treatment. RESULTS: Between December 2009 and June 2021, 545 of 2114 (25.8%) women diagnosed with a tubal pregnancy met our inclusion criteria. We compared women who underwent EM (N = 201) with women who received MTX (N = 344). All women in the EM group had a declining trend of hCG. The MTX group had higher pretreatment hCG and higher rates of yolk sac or embryo presence on ultrasound. Eventual surgical treatment rate was higher in the MTX group compared with the EM group (39 [11.3%] vs. 9 [4.5%], P = 0.006), with no difference in the treatment failure rate or tubal rupture rate. In a subgroup analysis of women with pretreatment hCG between 1000 and 2000 mIU/mL, eventual surgical treatment, treatment failure, and tubal rupture rates did not differ between groups. Logistic regression analysis revealed that eventual surgical treatment was independently associated with hCG levels less than 1000 mIU/mL (adjusted odds ratio [aOR] 0.28, 95% confidence interval [CI] 0.14-0.56) and endometriosis (aOR 9.20, 95% CI 3.55-23.81). CONCLUSION: Expectant management of tubal pregnancies with pretreatment hCG levels less than 2000 mIU/mL and even between 1000 and 2000 mIU/mL and with a declining trend of hCG demonstrated lower or comparable rates of eventual surgical treatment, when compared with MTX treatment.

Interstitial pregnancy management: A multicentric analysis of 98 patients from the FRANCOGENT group comparing surgery and medical treatment.

OBJECTIVE: To evaluate the outcomes associated with each therapeutic option for patients diagnosed with interstitial pregnancy (IP). METHODS: We conducted a multicentric retrospective cohort study within the departments of Gynecology and Obstetrics involved in the Francogent research group. Women treated for an interstitial pregnancy between January 2008 to December 2019 were included. Three therapeutic options were evaluated: surgical treatment (ST); in situ methotrexate combined with systemic methotrexate (IS-MTX); and systemic methotrexate (IM-MTX). Success of first-line treatment was defined by hCG negativation (<5I U/L). Secondary outcomes included the need for secondary surgical procedure, secondary medical treatment, emergency surgery, postoperative complications, duration of hospitalization, and delay before hCG negativation. RESULTS: A total of 98 patients were managed for IP: 42 (42.9%) patients had IM-MTX; 34 (34.7%) had IS-MTX; and 22 (22.4%) had ST. First-line treatment was successful in all patients of the ST group (22/22, 100%), in 31% of patients within the IM-MTX group (13/42) and 70.6% (24/34) in the IS-MTX group. The sole parameter associated with the risk of treatment failure was the mode of methotrexate administration. The size of the gestational sac or the presence of fetal heartbeat was not associated with decreased medical treatment (IS or IM-MTX) efficiency. CONCLUSION: Either ST or IS-MTX are good options for IP treatment associated with high success rates. A single-dose regimen of IM-MTX is less efficient than IS-MTX or ST. Symptomatic patients with severity criteria should always undergo emergency surgery. IP remains a high-risk condition that should be managed, whenever possible, in referral centers to potentialize the chances of favorable outcomes.

Prognostic factors for spontaneous resolution of an ectopic pregnancy.

OBJECTIVE: To identify factors that can accurately predict the spontaneous resolution of an ectopic pregnancy. STUDY DESIGN: This retrospective cohort analysis was conducted in the Department of Gynecology of a tertiary, university-affiliated medical center. Patients admitted to the center from January 2015 to July 2022 with a tubal ectopic pregnancy who met the criteria for expectant management were included. Beta-human chorionic gonadotropin (ß-hCG) levels were assessed at admission and at subsequent 24-hour intervals. Patients with declining levels were discharged for routine ambulatory ß-hCG follow-up until levels became undetectable. Patients who achieved a successful outcome were designated as the "spontaneous resolution group," while patients who underwent further hospitalization for methotrexate or surgery constituted the" failure group". Demographic, clinical, laboratory, and ultrasound parameters collected at first admission were compared between groups. RESULTS: Among the initial group of 210 eligible patients, 7 were lost to follow-up, 161 achieved spontaneous resolution, and 42 were readmitted for active intervention. Multivariate logistic regression analysis revealed that the last ß-hCG level before discharge (last ß-hCG) and the ratio between ß-hCG at discharge to ß-hCG at admission were the only independent parameters to predict outcomes. Patients with ß-hCG < 650 IU/L at discharge and a decline of 50% or more in ß-hCG level during hospitalization, had a 97% success rate with expectant management. Patients with ß-hCG discharge levels ≥ 1,000 IU/L had a 50% chance of success, regardless of whether their ß-hCG levels had declined. For all other patients, a 76% success rate was found. CONCLUSION: Short-term, serial ß-hCG follow-up at the initial presentation can help predict the spontaneous resolution of an ectopic pregnancy.

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

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

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

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

Evaluation of pretreatment and early treatment changes in serum ß-hCG with methotrexate.

BACKGROUND: Serum beta-human chorionic gonadotropin (ß-hCG) is an important biomarker for the detection of ectopic pregnancies (EPs). The ß-hCG levels between days 1 and 4 after methotrexate (MTX) treatment as an indicator of the success of the MTX in EP have been the focus of research. OBJECTIVES: To determine whether the change in the ß-hCG levels at day 1 and 4 and pretreatment at 48-hour increments can predict early treatment failure of single-dose MTX in EP. MATERIAL AND METHODS: This was a retrospective study of 1120 EPs treated with a single dose of MTX. Treatment failure was defined as an obligation to proceed to surgery or the need for additional doses of MTX. RESULTS: A total 722 out of 1120 EPs had an increase in ß-hCG on day 4 after MTX treatment. The logistic regression analysis indicated that 3 dependents were significantly associated with treatment failure: 1) a pretreatment 48-hour increase in ß-hCG (odds ratio (OR): 1.249, 95% confidence interval (95% CI): 1.008-2.049, p < 0.001); 2) a change in ß-hCG between day 1 and 4 (OR: 1.384, 95% CI: 1.097-2.198, p < 0.001); and 3) a history of EP (OR: 1.208, 95% CI: 1.041- 2.011, p < 0.001). The optimal cutoff point for the prediction of treatment failure was an increase of more than 19% in the 48 h before the treatment, and an increase of more than 36% between day 1 and day 4 in ß-hCG concentrations. Patients with an increase in ß-hCG levels of less than 36% on day 4 experienced MTX treatment failure in 4.2% (n = 25), compared to 74.5% (n = 88) of the patients with an increase above 36%. CONCLUSIONS: A serum ß-hCG increase of more than 36% on day 4 after the administration of MTX alongside a more than 19% increase in ß-hCG concentration 48 h before the MTX treatment may predict the early failure of medical treatment for an EP.

The importance of ß-hCG values in prediction of the effectiveness of single dose methotrexate therapy in tubal ectopic pregnancy.

OBJECTIVES: To investigate the importance of ß-hCG values on the day of onset and on the fourth and seventh day after treatment in the effectiveness of treatment in tubal ectopic pregnancies treated with a single dose of methotrexate (MTX). MATERIAL AND METHODS: One hundred sixty-two patients with tubal ectopic pregnancy treated with a single dose MTX treatment were retrospectively evaluated. ß-hCG values and changes on Days 0, 4 and 7 of the MTX treatment successful group and the unsuccessful group were analyzed. RESULTS: MTX treatment was successful in 125 (77.2%) and unsuccessful in 37. When the ß-hCG values on Days 0, 4 and 7 were compared in pairs, the differences between groups were statistically significant (p < 0.001). The mean ß-hCG value was 783.0 in the MTX successful group and 1802.0 in unsuccessful group (p < 0.001). There was a 21.6% decrease in ß-hCG values between Days 0 and day 4 in the MTX successful group and a 25.7% increase in the MTX unsuccessful group (p < 0.001). On Days 0, 4 and 7, ROC curve analysis's values are , respectively; 755/939/486 for cut off, 86.49/83.78/94.59% for sensitivity and 48.80/69.60/72.36% for specificity. CONCLUSIONS: Success rates of single-dose MTX treatment increase in tubal ectopic pregnancies with low initial ß-hCG value. Patients with a decrease in ß-hCG value and/or a cut-off decrease of 20% or more on the fourth day of treatment can be called for weekly ß-hCG monitoring without the need for close follow-up. The change in ß-hCG between Day 0 and Day 4 can be used to predict the efficacy of treatment.

Is local methotrexate therapy effective in the treatment of cesarean scar pregnancy? A retrospective cohort study.

AIM: To evaluate the success of local methotrexate (MTX) treatment, the side-effect profile and its fertility effect in patients diagnosed with cesarean scar pregnancy. MATERIALS: This retrospective cohort study included 56 cesarean scar pregnancy patients who applied to Erciyes University Faculty of Medicine, Department of Obstetrics and Gynecology between January 2012 and January 2022 and were treated with ultrasound-guided local MTX. The results of 56 patients with cesarean scar pregnancy who underwent transvaginal ultrasound-guided single-dose local MTX treatment were evaluated. First, the contents of the sac were aspirated, and then 50 mg of MTX was injected into the gestational sac. RESULTS: The median gestational age at diagnosis was 7 weeks 2 days. The mean beta human chorionic gonadotrophin level was 31 345 ± 37 838 (range: 113-233 835 mIU/mL). Fifty-four patients were successfully treated with local MTX therapy. The interval between the first MTX injection and the normalization of beta human chorionic gonadotrophin was 55.2 ± 41.0 days. None of our patients required surgical treatment. Beta human chorionic gonadotrophin values did not decrease in one patient and she was treated with systemic MTX. Local MTX therapy could not be applied to one patient for technical reasons. Only one patient needed blood transfusion after local MTX. Thirteen patients become pregnant after treatment (76%). No systemic side effects related to MTX were observed in any of the patients. CONCLUSION: Transvaginal ultrasound-guided single-dose local MTX treatment is an effective, safe, and fertility-preserving treatment method for cesarean scar pregnancy.

Experience of a Tertiary Service in the Treatment of Women with Cervical Pregnancy.

OBJECTIVE: Cervical pregnancy is challenging for the medical community, as it is potentially fatal. The treatment can be medical or surgical; however, there are no protocols that establish the best option for each case. The objective of the present study was to describe the cases of cervical pregnancy admitted to a tertiary university hospital over a period of 18 years. METHODS: A retrospective study based on a review of the medical records of all cervical pregnancies admitted to the Women's Hospital at Universidade Estadual de Campinas, Southeastern Brazil, from 2000 to 2018. RESULTS: We identified 13 cases of cervical pregnancy out of a total of 673 ectopic pregnancies; only 1 case was initially treated with surgery because of hemodynamic instability. Of the 12 cases treated conservatively, 7 were treated with single-dose intramuscular methotrexate, 1, with intravenous and intramuscular methotrexate, 1, with intravenous methotrexate, 1, with 2 doses of intramuscular methotrexate, and 2, with intra-amniotic methotrexate. Of these cases, one had a therapeutic failure that required a hysterectomy. Two women received blood transfusions. Four women required cervical tamponade with a Foley catheter balloon for hemostasis. There was no fatal outcome. CONCLUSION: Cervical pregnancy is a rare and challenging condition from diagnosis to treatment. Conservative treatment was the primary method of therapy used, with satisfactory results. In cases of increased bleeding, cervical curettage was the initial treatment, and it was associated with the use of a cervical balloon for hemostasis.

OBJETIVO: A gravidez ectópica cervical é um desafio para a comunidade médica, pois pode ser fatal. O tratamento pode ser clínico ou cirúrgico, mas não existem protocolos que estabeleçam a melhor opção para cada caso. O objetivo deste estudo foi descrever os casos de gravidez ectópica cervical internados em um hospital universitário terciário durante 18 anos. MéTODOS: Estudo retrospectivo com revisão de prontuários de todas as gestações ectópicas cervicais internadas no Hospital da Mulher da Universidade Estadual de Campinas de 2000 a 2018. RESULTADOS: Foram identificados treze casos de gestação ectópica cervical em um total de 673 gestações ectópicas; apenas 1 caso foi inicialmente tratado com cirurgia por causa de instabilidade hemodinâmica. Dos 12 casos tratados conservadoramente, 7 foram tratados com metotrexato por via intramuscular em dose única, 1, com metotrexato pelas vias intravenosa e intramuscular, 1, com metotrexato por via intravenosa, 1, com 2 doses de metotrexato por via intramuscular, e 2, com metotrexato por via intra-amniótica. Desses casos, um apresentou falha terapêutica, e realizou-se uma histerectomia. Duas mulheres receberam transfusões de sangue. Quatro mulheres necessitaram de tamponamento cervical com cateter balão de Foley para hemostasia. Não houve casos fatais. CONCLUSãO: A gravidez cervical é uma condição rara e desafiadora desde o diagnóstico até o tratamento. O tratamento conservador foi o principal método terapêutico utilizado, com resultados satisfatórios. Nos casos de sangramento aumentado, a curetagem cervical foi o tratamento inicial, e foi associada ao uso de balão cervical para hemostasia.

Future Perspectives of Ectopic Pregnancy Treatment-Review of Possible Pharmacological Methods.

Ectopic pregnancy, that is, a blastocyst occurring outside the endometrial cavity of the uterus, affects nearly 2% of pregnancies. The treatment of ectopic pregnancy is surgical or pharmacological. Since surgical management is associated with numerous serious side effects, conservative treatment is sought. The treatment of choice in the majority of cases is based on pharmacotherapy with methotrexate (MTX) in a single- or multi-dose regimen. Although the efficacy of methotrexate reaches between 70 and 90%, its use requires specific conditions regarding both the general condition of the patient and the characteristic features of the ectopic pregnancy. Moreover, MTX can cause severe adverse effects, including stomatitis, hepatotoxicity and myelosuppression. Therefore, clinicians and researchers are still looking for a less toxic, more effective treatment, which could prevent surgeries as a second-choice treatment. Some studies indicate that other substances might constitute a good alternative to methotrexate in the management of ectopic pregnancies. These substances include aromatase inhibitors, especially letrozole. Another promising substance in EP treatment is gefitinib, an inhibitor of EGFR tyrosine domain which, combined with MTX, seems to constitute a more effective alternative in the management of tubal ectopic pregnancies. Other substances for local administration include KCl and absolute ethanol. KCl injections used in combination with MTX may be used when foetal heart function is detected in cervical ectopic pregnancies, as well as in heterotopic pregnancy treatment. Absolute ethanol injections proved successful and safe in caesarean scar pregnancies management. Thus far, little is known about the use of those substances in the treatment of ectopic pregnancies, but already conducted studies seem to be promising.

Time to resolution of tubal ectopic pregnancy following methotrexate treatment: A retrospective cohort study.

OBJECTIVE: To determine the time to resolution of tubal ectopic pregnancy after methotrexate treatment. METHODS: A 14-year retrospective cohort study was performed from 2004-2018 and assessed 216 women treated with single-dose methotrexate for tubal ectopic pregnancy. Women were treated using a single-dose protocol of intramuscular methotrexate (50mg/m2) for confirmed tubal ectopic pregnancy on ultrasound. Ectopic pregnancies were included if the ectopic pregnancy mass was <35mm, no evidence of rupture and no embryonic cardiac activity. Serum hCG was measured on day 1, 4 and 7 of treatment and then at standard weekly intervals until resolution. Where there was not a ≥15% decline in hCG from day 4 and day 7, a second dose of methotrexate was administered. The primary outcome was time to resolution (days), with serum hCG <5 IU/L considered resolved. The secondary outcome was need for rescue surgery. RESULTS: Among women who did not proceed to surgery, the median time to resolution was 22 days (IQR 14,34). Time to resolution and need for rescue surgery increased with baseline hCG. When hCG was <1000 IU/L, the median was 20 days (IQR 13,29) but 34.5 days (IQR 22,48) with hCG >2000 IU/L. Early hCG trends were predictive of time to resolution and likelihood of rescue surgery; a hCG rise of >1000 IU/L between Days 1-4 increased time to resolution to 61 days (IQR 35,80) and an odds ratio of rescue surgery of 28.6 (95% C.I. 5.3,155.4). CONCLUSION: The median time to resolution for ectopic pregnancies treated with methotrexate is 22 days and associated with baseline hCG levels. The predictive value of baseline hCG may be useful in clinical decision making and counselling women considering methotrexate for ectopic pregnancy.

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

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

Ectopic pregnancy: a single-center experience over ten years.

PURPOSE: The aim of this study was to investigate characteristics associated with ectopic pregnancy (EP) that could be utilized for predicting morbidity or mortality. METHODS: This was a retrospective analysis of pregnancy-related records from a tertiary center over a period of ten years. Data on age, gravidity, parity, EP risk, amenorrhea duration, abdominal pain presence and location, ß-human chorionic gonadotropin (ß-HCG) level, ultrasound findings, therapeutic intervention, exact EP implantation site and length of hospital stay (LOS) were obtained from the database. The LOS was used as a proxy for morbidity and was tested for an association with all variables. All statistical analyses were conducted with Stata® (ver. 16.1, Texas, USA). RESULTS: The incidence of EP in a cohort of 30,247 pregnancies over a ten-year period was 1.05%. Patients presented with lower abdominal pain in 87.9% of cases, and the likelihood of experiencing pain was tenfold higher if fluid was detectable in the pouch of Douglas. Only 5.1% of patients had a detectable embryonic heartbeat, and 18.15% had one or more risk factors for EP. While most EPs were tubal, 2% were ovarian. The LOS was 1.9 days, and laparoscopic intervention was the main management procedure. The cohort included one genetically proven dizygotic heterotopic pregnancy (incidence, 3.3 × 10- 5) that was diagnosed in the 7th gestational week. The only association found was between the ß-HCG level and LOS, with a linear regression ß coefficient of 0.01 and a P-value of 0.04. CONCLUSION: EP is a relatively common condition affecting approximately 1% of all pregnancies. ß-HCG correlates with EP-related morbidity, but the overall morbidity rate of EP is low regardless of the implantation site. Laparoscopic surgery is an effective therapeutic procedure that is safe for managing EP, even in cases of heterotopic pregnancy.

Pain Associated With Cervical Priming for First-Trimester Surgical Abortion: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of cervical priming with mifepristone with that of misoprostol on pain perception during surgical induced abortion under paracervical block. METHODS: We conducted a randomized, single-blind, two-center study of women undergoing surgical induced abortion at less than 14 weeks of gestation under paracervical block. Participants were randomized to receive cervical priming with 200 mg of oral mifepristone 36 hours or 400 micrograms buccal misoprostol 3 hours before surgery. The primary outcome was pain during mechanical cervical dilation evaluated by a 100-mm visual analog scale (VAS). Secondary outcomes were pain during aspiration, preoperative and postoperative pain, participant satisfaction, duration of the procedure, occurrence of complications, and ease of performing the procedure (assessed by a 100-mm VAS). We estimated that 110 women would have to be included to have 90% power to detect a 13mm-difference of VAS for pain. RESULTS: Between June 2017 and May 2019, 314 women were eligible and 110 were randomized (55 in each group). Patient characteristics were similar in the two groups. The mean VAS score during mechanical cervical dilation was lower in the mifepristone group (35.6±21 vs 43.5±21, P=.04) as was the mean VAS during aspiration (34±24 vs 47.8±23, P=.003). The preoperative and postoperative mean VAS, satisfaction and duration of procedures were similar between groups. The procedure was significantly easier to perform in the mifepristone group (88±16 vs 80±23, P=.004). CONCLUSION: Cervical priming with mifepristone for surgical induced abortion under paracervical block up to 14 weeks of gestation is more effective than misoprostol in reducing pain perception. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03043014.

hCG values and gestational sac size as indicators of successful systemic methotrexate treatment in cesarean scar pregnancy.

OBJECTIVE: To retrospectively investigate cesarean scar pregnancy (CSP) patients who received systemic methotrexate (MTX) and to clarify the criteria for administering systemic MTX to CSP patients. MATERIALS AND METHODS: Fifteen CSP patients who were initially treated with systemic MTX (50 mg/m2/week) were included. Nine patients, who needed a uterine artery embolization (UAE) or a laparotomy, including a transabdominal hysterectomy (TAH), were defined as the unsuccessful MTX group. Six patients who did not require UAE or a laparotomy were defined as the successful MTX group. Furthermore, the hCG cut-off value and the GS cut-off size at the time of CSP diagnosis, which differentiated successful and unsuccessful patients, were defined. MTX success rates were investigated by combining the hCG and gestational sac (GS) size cut-off values. RESULTS: The hCG cut-off value was 17757.0 mIU/mL, and the GS cut-off size was 10.4 mm. In patients with hCG values less than 17757.0 mIU/mL, the MTX success rate was 75.0%. Fewer patients needed UAE or a laparotomy compared to patients with hCG values higher than 17757.0 mIU/mL (P = 0.007). In patients with a GS size less than 10.4 mm, the MTX success rate was 80.0%. Fewer patients among them needed UAE or a laparotomy compared to those among patients with a GS size greater than 10.4 mm (P = 0.089). In patients with hCG values and GS sizes lower than the cut-off values, the MTX success rate was 80.0%. Fewer patients among them needed UAE or a laparotomy compared to those among patients with hCG values and/or GS sizes higher than the cut-off values, respectively (P = 0.010). CONCLUSION: Patients with hCG values less than 17757.0 mIU/mL and GS sizes less than 10.4 mm may have a greater chance of successful systemic MTX treatment when it is used as the first line of treatment for CSP.

A scary complication: single-center study on management and outcome of cesarean scar pregnancy

Abstract A cesarean scar pregnancy (CSP) is a scary and life-threatening complication of cesarean section (CS). Nevertheless, the incidence of CS is constantly growing. The CSP incidence is 0,15% of pregnancies after CS which represents 6,1% of all ectopic pregnancies in women with condition after CS. Therefore, it should be more present in the clinical daily routine. From mild nonspecific symptoms to hypovolemic shock, diagnosis and therapy must be performed quickly. With the progressive growth of the scar pregnancy, a uterine rupture involves the risk of severe bleeding, and an emergency hysterectomy could be necessary. Prolongation of pregnancy has been successful only in a few cases.We report 11 cases from our hospital in the past 10 years. In the discussion, treatment options of this complication with an increasing incidence, which is associated with serious morbidity and mortality, are presented based on the current literature. Treatment options include drug therapy, but also surgical or combined procedures with radiological intervention.

Increase rate of ruptured tubal ectopic pregnancy during the COVID-19 pandemic.

OBJECTIVE: During the 2020 COVID-19 pandemic there was a decrease in emergency room arrivals. There is limited evidence about the effect of this change in behavior on women's health. We aimed to evaluate the impact of the COVID-19 pandemic on the diagnosis, treatment and complications of women presenting with a tubal Ectopic Pregnancy (EP). STUDY DESIGN: This is a single centre retrospective cohort study. We compared the clinical presentation, treatment modalities and complications of all women presenting in our institution with a tubal EP during the COVID-19 pandemic between 15 March and 15 June 2020, with women who were treated in our institution with the same diagnosis in the corresponding period for the years 2018-2019. RESULTS: The study group included 19 cases of EP (N = 19) that were treated between the 15 March 2020 and 15 June 2020. The control group included 30 cases of EP (N = 30) that were admitted to in the corresponding period during 2018 and 2019. Maternal age, parity, gravity and mode of conception (natural vs. assisted) were similar between the two groups. There was no difference in the mean gestational age (GA) according to the last menstrual period. In the study group more women presented with sonographic evaluation of high fluid volume in the abdomen than in the control group (53 % vs 17 %, P value 0.01). This finding is correlated with a more advanced disease status. In the study group there was a highly statistically significant 3-fold increase in rupture among cases (P < 0.005) and a 4-fold larger volume of blood in the entrance to the abdomen (P < 0.002). We found that there were no cases of ruptured EP in the group of women who were pregnant after assisted reproduction. CONCLUSION: We found a higher rate of ruptured ectopic pregnancies in our institution during the COVID-19 pandemic. Health care providers should be alerted to this collateral damage in the non-infected population during the COVID-19 pandemic.