Single-dose Methotrexate Protocol Research Articles

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

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

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

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

Prediction of Rupture by Complete Blood Count in Tubal Ectopic Pregnancies Treated with a Single-Dose Methotrexate Protocol.

The availability of reliable and inexpensive markers that can be used to determine the risk of rupture during methotrexate (MTX) treatment in ectopic pregnancies (EPs) is considerable. The aim of the present study is to investigate the role of systemic inflammatory markers such as leukocytes (or white blood cells, WBCs), the neutrophil-to-lymphocyte ratio (NLR), and platelet distribution width (PDW), which are among the parameters of the complete blood count (CBC), in the prediction of rupture of EPs under MTX treatment. A total of 161 patients with tubal EP who underwent a single-dose methotrexate (MTX) protocol were retrospectively analyzed, and the control group (n = 83) included patients cured by MTX, while the ruptured group (n = 78) included patients who were operated on for tubal rupture during the MTX treatment. The features of EP, beta-human chorionic gonadotropin (β-hCG) levels, sonographic findings, and CBC-derived markers such as WBC, NLR, and PDW, were investigated by comparing both groups. The NLR was found to be higher in the ruptured group, of 2.92 ± 0.86%, and significantly lower in the control group, of 2.09 ± 0.6%. Similarly, the PDW was higher (51 ± 9%) in the ruptured group, and it was significantly lower a (47 ± 13%) in the control group (p < 0.05). Other CBC parameters were similar in both groups (p > 0.05). Systemic inflammation markers derived from CBC can be easily applied to predict the risk of tubal rupture in Eps, since the CBC is an inexpensive and easy-to-apply test, which is first requested from each patient during hospitalization.

Do the change in β-hCG values between the 0th and 4th days in tubal ectopic pregnancy treatment with a single-dose methotrexate (MTX) protocol predict the need for a second dose of MTX?

The single-dose methotrexate (MTX) regimen is effective and minimizes side effects but an additional second dose is needed in case of failure in an ectopic pregnancy (EP). We aimed to predict the additional MTX dose by evaluating the change in β-hCG values between day 0 and day 4 in EPs with administered single-dose MTX regimen. A total of 454 tubal EPs between 2013 and 2019 were evaluated retrospectively. Cases cured with a single dose of MTX without an additional dose were accepted as the control group, and cases under a single-dose regimen were cured by applying a second dose of MTX on the 7th day were accepted as the study group. Obstetric and demographic characteristics and the change in β-hCG values compared in both groups. Age, body mass index (BMI), gravida, smoking, abdominal surgery, presence of IUDs, initial β-hCG levels (0th day), and EP size were similar in both groups, but the presence of previous EP history was significantly higher in the study group. The change of β-hCG from days 0 and 4 determined that a 20% increase predicts the need for a second dose of MTX with 72.4% sensitivity, and 87.8% negative predictive value (NPV). The single-dose MTX protocol is successful in 83.3% of convenient cases (as the control group), but an increase of 20% in β-hCG between days 0 and 4 predicts the patients who need to be administered second-dose MTX, and thus, a double-dose MTX protocol will be achieved early.

8575 Single Dose Methotrexate, Predicting Outcomes at Time of Second Dose

<h3>Study Objective</h3> The single dose methotrexate protocol, which may include additional doses, is an accepted option for treating ectopic pregnancies. The objective of this study was to determine what percentage of patients administered a second dose of methotrexate fail this regimen and undergo laparoscopy. Additionally, we defined patient characteristics that may influence the decision to pursue surgery. <h3>Design</h3> Retrospective cohort study. <h3>Setting</h3> High volume academic, tertiary medical center. <h3>Patients or Participants</h3> Patients with an ectopic pregnancy from July 2011 to July 2021 that underwent medical treatment with single dose methotrexate 50 mg/m² IM and subsequently received a second dose of methotrexate. <h3>Interventions</h3> Laparoscopic tubal surgery for ectopic pregnancy. <h3>Measurements and Main Results</h3> Over 10 years, 167 patients were given a second injection of methotrexate following their initial methotrexate dose. Of those, 35/167 (21%) patients underwent surgery. In those who underwent surgery 12/35 (34.3%) had a ruptured ectopic pregnancy, of whom 5/12 (41.7%) had a significant hemoperitoneum (≥500 ml). In patients with a documented ultrasound prior to the second dose of methotrexate, 26 of the 94 (27.7%) women with an adnexal mass had subsequent surgery compared to 9 of the 68 (13.2%) without a mass, RR of 2.12 (P=0.03). No other demographic or surgical risk factors (i.e. BMI, smoking status, history of abdominal surgery, diabetes, or prior ectopic pregnancy) impacted the risk of undergoing surgical management. <h3>Conclusion</h3> Of all women receiving a second dose following planned single dose methotrexate therapy, 79% were successfully medically managed. Patients with an adnexal mass on ultrasound had more than double the relative risk of undergoing surgery (27.7%) and should be counseled accordingly.

Can the Additional Dose Requirement be Determined before the Seventh Day to Successfully Treat Tubal Ectopic Pregnancy with a Single-dose Methotrexate Protocol?

To investigate the relationship of beta-hCG changes between the first, fourth and seventh days as a predictor of the additional dose requirement in single-dose methotrexate protocol in tubal ectopic pregnancy. Observational study. Department of Obstetrics and Gynecology, Bursa Yüksek İhtisas Training and Research Hospital, between January 2017 and June 2020. Data of 123 patients with tubal ectopic pregnancy, treated with a single-dose methotrexate protocol, were retrospectively analysed. Patients who received methotrexate on the first day and achieved treatment success constituted one group. Patients who received additional doses on the seventh day and achieved treatment success, constituted the other group. Treatment success was defined as normalisation of beta-hCG levels without surgical intervention. The percentage of beta-hCG change between day-one and day-four was a significant independent variable for the additional dose treatment requirement (OR:1.07, CI:1.01-1.13, p=0.022). The cut-off value of the beta-hCG change percentage between the first and fourth day, was calculated as 4% (sensitivity 72.9%, specificity 78.9%, positive predictive value [PPV] 88.6%, negative predictive value [NPV] 56.6%). In the single-dose methotrexate protocol applied in the medical treatment of tubal ectopic pregnancy, the change in beta-hCG value between the first and fourth days may predict the need for additional doses. Administration of an additional dose of methotrexate on the fourth day may be considered, if there is less than a 4% decrease or any increase in beta-hCG value between the first and fourth days. Key Words: Ectopic pregnancy, Methotrexate, Beta human chorionic gonadotropin, Tubal pregnancy, Single-dose protocol.

Day 1 change in maternal serum β-HCG levels as an early predictor of successful medical therapy in ectopic pregnancies

Objective: To evaluate the role of β-HCG level changes between days 0 and 1 as an early predictor of methotrexate success in cases of tubal ectopic pregnancy.Methods: A retrospective study included 86 tubal ectopic pregnancies treated with a single-dose methotrexate protocol of 50 mg/m2 of body surface. β-HCG measurements were taken on days 0, 1, 4 and 7 where day 0 is the day of methotrexate injection. Day 0 β-HCG and the percentage change in β-HCG level between days 0 and 1 (HCG index) were calculated and compared between patients who were successfully or unsuccessfully treated. Receiver operator characteristics (ROC) curves were plotted to identify the best cutoff levels.Results: The average level of β-HCG (1416.8 versus 2502.5 IU/L, p=.001) and its increment after 24 hours (12.9 versus 27.1%, p=.001) were significantly lower in the successful treatment group. ROC curves for β-HCG level and its relative increment revealed that cutoff values of ≤1550 IU/L and ≤13% increment showed a sensitivity of 90 and 70% respectively for successful methotrexate treatment.Conclusion: Day 0 β-HCG level ≤1550 IU/L and an increment of ≤13% after 24 hours are early predictors of successful methotrexate treatment for tubal ectopic pregnancy.

Systematic review and meta-analysis of single-dose and non-single-dose methotrexate protocols in the treatment of ectopic pregnancy.

It remains unclear which methotrexate protocol for the treatment of ectopic pregnancy has a higher success rate or a higher adverse effect rate. To compare the treatment success rates and adverse effect rates of single-dose and non-single-dose (two-dose and multi-dose) methotrexate protocols in the treatment of ectopic pregnancy. Various databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched on July 1, 2017, using search terms including "methotrexate" and "pregnancy." Randomized controlled trials comparing different methotrexate protocols for the treatment of ectopic pregnancy were included. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare treatment success rates and adverse effect rates. The single-dose and non-single-dose protocols had similar success rates (RR 1.00, 95% CI 0.96-1.04; 11 trials, 1121 patients, I2 =18%). The non-single-dose protocols had a higher adverse effect rate than did the single-dose protocol (RR 0.73, 95% CI 0.59-0.91; nine trials, 934 patients, I2 =0%). The single-dose methotrexate protocol was the optimal protocol for the medical treatment of ectopic pregnancy.

Predictors of failure of the commonly used single-dose methotrexate protocol for treating tubal ectopic pregnancies

ObjectivesThis study identified patients who would benefit from an earlier additional medical intervention and/or continuing close surveillance even if commonly used parameters indicated sufficient medical treatment to determine markers of treatment failure. Materials and methodsA retrospective analysis of patients with a preliminary diagnosis of ectopic pregnancy treated with the single-dose methotrexate protocol. Group 1: cases cured with a single dose of methotrexate; Group 2: cases who required more than one dose of methotrexate or surgery following the first dose. Demographics, clinical/sonographic findings, observation period, and β-human chorionic gonadotropin (hCG) levels were compared among the two groups. Thresholds were defined and a regression analysis was performed to define independent predictors of failure. ResultsData from 120 patients were analyzed: Group 1 (n = 92); Group 2 (n = 28). β-hCG levels measured at all time points, and day (0–4) and day (4–7) changes, presence of adnexial masses, and infertility were significantly different among the two groups. Only the day (0–4) and day (4–7) changes in β-hCG levels were independent predictors of failure. ConclusionDay (0–4) thresholds or newly defined day (4–7) thresholds were not more sensitive than the conventional day (4–7) criteria. Day (0–4) β-hCG levels increased by more than 9.7% in half the patients who required additional methotrexate doses or surgery despite fulfillment of the conventional day (4–7) criteria. In contrast, no cases of treatment failure were observed if the day (0–4) decrease was >26.6%.

Role of day 4 HCG as an early predictor of success after methotrexate therapy for ectopic pregnancies

ObjectiveTo validate whether change in serum HCG levels between days 0 and 4 confer any prognostic value during methotrexate therapy and to quantify its change. Study designThis is a retrospective study of 48 tubal ectopic pregnancies treated with single dose methotrexate protocol at University Hospital, Muscat, Oman from January 2012 to December 2013. The clinical outcome was analyzed based on the complete resolution of HCG levels or need for additional doses of methotrexate or recourse to surgery. The percentage change in HCG levels between days 0 and 4 (HCG index) of methotrexate were calculated and receiver operator characteristics curve was plotted to identify the best cutoff levels. In order to get a robust 95% confidence interval, bootstrap method using R software was done using 1000 re-sampling. ROC curve and the predictive values were estimated using MEDCALC software. ResultsThe mean HCG level on day 4 is significantly higher in treatment failure group (4254±4095 IU/L vs. 2109±3646 IU/L, P=0.008). The HCG levels between day 0 and 4 decreased in 42.7% (21/48) of cases and 80.9% of these cases had treatment success. The HCG levels increased in 57.4% (27/48) of cases and 33.3% of these cases had treatment success. (P=0.001). A 10 percent decline in day 4 HCG levels predict the treatment success with sensitivity of 77% and Specificity 81%. The area under the ROC curve was 0.82 (95% CI: 0.67–0.92), (P<0.001). ConclusionThe success with single dose of methotrexate therapy for tubal ectopic pregnancies was predicted early in the course of treatment by following three key findings: the absolute mean HCG values on day 4, decrease in HCG level from day 0 to 4 and 10% or more fall in day 4 HCG levels.

Adherence to the Single-Dose Methotrexate Protocol for the Management of Ectopic Pregnancy in an Inner City Population: A retrospective cohort and protocol analysis

Adherence to the Single-Dose Methotrexate Protocol for the Management of Ectopic Pregnancy in an Inner City Population: A retrospective cohort and protocol analysis

Predictive factors for the methotrexate treatment outcome in ectopic pregnancy: A comparative study of 400 cases

ObjectiveWe sought to evaluate the global success rate of intramuscular methotrexate for the treatment of ectopic pregnancy, identify factors predictive of treatment success or failure, and study methotrexate tolerability in a large patient cohort. Study designFor this single-center retrospective observational study, we retrieved the records of all women who had a clinically or echographically confirmed ectopic pregnancy with a Fernandez score <13 and who were treated according to a 1mg/kg intramuscular single-dose methotrexate protocol. Medical treatment failure was defined by an obligation to proceed to laparoscopy. Needing a second injection was not considered to be medical treatment failure. ResultsBetween February 2008 and November 2013 (69 months), 400 women received methotrexate for ectopic pregnancy. The medical treatment protocol was effective for 314 patients, i.e., an overall success rate of 78.5%. A single methotrexate dose was sufficient for 63.5% of the women and a second dose was successful for 73.2% of the remaining women. The medical treatment success rate fell as initial hCG levels climbed. The main factors associated with methotrexate failure included day (D) 0, D4 and D7 hCG levels, pretherapeutic blood progesterone, hematosalpinx at D0 and pain at D7. Early favorable kinetics of hCG levels was predictive of success. Methotrexate treatment was successful in 90% of women who had D0 hCG <1000IU/l. Methotrexate tolerability was good, with only 9% of the women reporting non-severe adverse effects. The fertility rate with delivery after medical treatment for ectopic pregnancy was 80.7%. ConclusionIn this study, we showed that an initial hCG value <1000IU/l and favorable early HCG kinetics were predictive factors for the successful medical treatment of ectopic pregnancy by methotrexate, and hematosalpinx and pretherapeutic blood progesterone >5ng/ml at diagnosis were predictive of its failure. We also confirmed good tolerability for single-dose methotrexate protocols.

Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes

Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P < .001, P=.011, P < .001, and P= .035, respectively). Women had similar initial human chorionic gonadotropin levels in either protocol but the mean rate of decline of human chorionic gonadotropin from day 0 (day of administration of first dose of methotrexate) to day 7 was significantly more rapid in women who received the single-dose protocol compared to those treated with the 2-dose protocol (mean change -31.3% vs -10.4%, P= .037, adjusted for propensity score and site). The 2 protocols had no significant differences in success rate or time to resolution. In a racially and geographically diverse group of women, the single- and double-dose methotrexate protocols had comparable outcomes. The more rapid human chorionic gonadotropin initial decline in the single-dose group suggested these patients were probably at lower risk for ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication.

Methotrexate treatment in progressive tubal ectopic pregnancies and hCG-related clinicosurgical implications

Our aim was to evaluate the relationship between the success of methotrexate treatment and β-hCG levels in progressive tubal ectopic pregnancies. We defined a retrospective cohort of 394 progressive tubal ectopic pregnancy patients treated with methotrexate. A single-dose methotrexate protocol using 50 mg/m2 was administered to patients with progressive tubal ectopic pregnancy. Surgery was performed in patients who exhibited signs of acute abdomen due to tubal rupture. Of 394 patients that received methotrexate treatment, 335 (84.6%) responded to medical treatment, while the remaining 59 (15.36%) underwent surgery due to treatment failure. β-hCG levels in the failure group were significantly higher as compared with the success group at Day 1, Day 4, and Day 7 (2116±3157 vs. 4178±3422, 2062±3551 vs. 4935±4103, and 1532±3007 vs. 3900±4783, respectively). The receiver operating characteristics curve for β-hCG levels at Day 1 was 0.738, with a cutoff value of 1418 mIU/mL, while sensitivity and specificity values reached the optimum for treatment success (83.1% and 59.4%, respectively). Medical treatment with methotrexate achieved an 85.02% success rate for the treatment of progressive tubal ectopic pregnancy, while success rates for medical treatment decreased significantly when initial β-hCG levels were >1418 mIU/mL.

Is Day 4 β-hCG an Early Predictor of Single-Dose Methotrexate Protocol in the Management of Tubal Ectopic Pregnancies? [299

INTRODUCTION: A single-dose methotrexate protocol was validated and successfully used to preserve fertility in ectopic pregnancy. A 15% drop in β-hCG between days 4 and 7 had a positive predictive value of 93% in predicting success. However, the drawback of this protocol is there is a waiting period of 7 days before we know whether the methotrexate is effective. Hence, we aim to examine whether a rise or fall in serum β-hCG from days 0–4 confers any prognostic value during methotrexate therapy. METHODS: This is a retrospective study of tubal ectopic pregnancies treated with a single-dose methotrexate protocol at Sultan Quboos University Hospital, Muscat, Oman, for 2 years from 2012 to 2013. We categorized our data into group 1 and group 2 based on whether serum β-hCG rose or fell between days 0 and 4, respectively. We analyzed the data for treatment success or failure. RESULTS: Forty-eight eligible women who received a single-dose methotrexate protocol for ectopic pregnancy were analyzed. The overall treatment success rate was 70.83% (34/48). Of 21 patients in whom serum β-hCG dropped between days 0 and 4 after methotrexate, the ectopic pregnancy was resolved in 95.23% of cases without further treatment. Of 27 women in whom serum β-hCG rose between days 0 and 4, only 51.85% had treatment success. CONCLUSION: A decrease in β-hCG levels between days 0 and 4 after methotrexate for ectopic pregnancy appears to be a reliable indicator of treatment success.

Patient Adherence to Medical Management of Ectopic Pregnancy

INTRODUCTION: Ectopic pregnancies comprise approximately 1–2% of all pregnancies. Single-dose methotrexate is an acceptable treatment for nonruptured ectopic pregnancies. Less than one in five inner-city underserved patients comply with follow-up protocols after methotrexate. Alternative protocols with less follow-up visits are available but are not currently the standard of care secondary to less known morbidity and failure. The objective of this study was to evaluate adherence to an established single-dose methotrexate protocol, specifically typical follow-up and associated morbidity in inner-city patients. METHODS: We performed a retrospective chart review of patients treated for ectopic pregnancy with methotrexate from January 2009 to December 2012. Data were collected on demographics, medical history, barriers to follow-up, dates of follow-up, human chorionic gonadotropin levels, methotrexate doses given, and surgical interventions. RESULTS: A total of 125 patients were included. No specific follow-up trend existed, but 75% of patients followed up for one additional blood draw as follows: day 4 (41%), day 8 (33.3%), day 5 (31.7%), and day 7 (27.5%). Recommend follow-up on both days 4 and 7 was only 18.3%. No significant differences in morbidity or treatment failure were associated with patterns of follow-up. CONCLUSIONS: Overall adherence to an established methotrexate protocol is poor. Patient follow-up did occur but not per the recommended protocol. Treatment success was not affected by nonadherence, suggesting that alternative protocols may be safely considered. Further evaluation of alternative protocols to improve compliance and confirm safety is recommended.

Role of routine monitoring of liver and renal function during treatment of ectopic pregnancies with single-dose methotrexate protocol

To assess whether or not baseline serum transaminases and creatinine measurements, before administration of methotrexate, identified significant liver or kidney disease, which have the potential to alter the management plan for the treatment of ectopic pregnancies. This is a retrospective study of patients treated for ectopic pregnancy. Women's emergency room and reproductive endocrinology office at a teaching hospital over a 3-year period. Women presenting for treatment of ectopic pregnancy. None. Assessment of baseline serum transaminases and creatinine measurements before administration of methotrexate to identify significant liver or kidney disease. A total of 383 patients were managed for ectopic pregnancy from January 2006 to December 2008. Of these, 320 patients received methotrexate as part of their treatment. No patient was denied treatment with methotrexate secondary to concerns regarding liver or renal function. No complication related to methotrexate administration was documented. A subgroup of 81 patients had pre- and postadministration labs, and no significant difference was noted upon comparing the values. Routine measurement of serum aspartate aminotransferase and creatinine levels may not be necessary before instituting a single-dose methotrexate treatment regimen for the management of ectopic pregnancy.

Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy

Objective To compare efficacy between double-dose methotrexate and single-dose methotrexate for treatment of tubal ectopic pregnancy (EP). Methods Between March 2008 and February 2011,157 patients who had tubal EP diagnosed by a non-laparoscopic approach and were hemodynamically stable were enrolled in a prospective study in Qassim, Saudi Arabia. The participants were randomized to receive either double-dose (50 mg/m 2 intramuscularly on days 0 and 4; group 1) or single-dose (50 mg/m 2 intramuscularly on day 0; group 2) methotrexate. Serum human chorionic gonadotropin (β-hCG) levels were followed until negative. Results The overall success rate was comparable between groups 1 and 2 (88.6% versus 82.0%, P = 0.1). The duration of follow up until negative β-hCG was shorter in group 1 ( P = 0.001). Receiver operative characteristics showed that higher cut-off levels of β-hCG and gestational mass diameter were associated with successful outcome in group 1. Among participants with initial β-hCG of 3600–5500 mIU/mL, the success rate was higher in group 1 ( P = 0.03). There was no significant difference between groups in adverse effects. Conclusion For treatment of EP, double-dose methotrexate had efficacy and safety comparable to that of single-dose methotrexate; it had better success among patients with moderately high β-hCG and led to a shorter follow up.

Methotrexate failure in women with prior ectopic: our experience with the two-dose methotrexate protocol

OBJECTIVE: Methotrexate (MTX) therapy of ectopic pregnancy (EP) is safe and effective in appropriate cases. Previous data suggest that women with previous EP have an increased failure rate when treated with a single-dose MTX protocol. Our objective was to investigate if previous EP remained a risk factor for MTX failure in our population where most women receive a two-dose MTX protocol. DESIGN: Retrospective cohort MATERIALS AND METHODS: Data were abstracted from all cases of confirmed EP between 1999 and 2007 regarding presentation, evaluation, treatment, and history of EP. Parametric and non-parametric methods were used to compare variables; multivariable logistic regression was used to assess the effect of prior EP on MTX failure. RESULTS: We identified 202 cases primarily treated with MTX; 17.3% had a history of EP, 83% received 2-dose MTX therapy. There was no difference between women with and without previous EP in bleeding, pain, or gestational age at presentation, or days from presentation to MTX. The overall risk of MTX failure was 16.3%. The unadjusted OR for MTX failure in women with prior EP vs no EP was 2.06 (95%CI 0.75,5.24; p=0.10). In adjusted models the association between MTX failure and prior EP differed depending on the ultrasound (u/s) at presentation (interaction p =0.04). When the u/s was suspicious for EP (free fluid, mass) no increased risk of MTX failure with prior EP was observed (OR=0.44, 95%CI: 0.07, 2.77; p=0.38). However, in those with a non-diagnostic u/s, prior EP increased the odds of MTX failure by 5.65 (95%CI: 1.16, 27.48; p=0.03). HCG level at treatment also carried an increased odds of MTX failure (p=0.002). CONCLUSIONS: Prior EP is a risk factor for MTX failure in women in our population who present with a non-diagnostic u/s. It is important to recognize these women as higher risk, and both monitor and counsel these patients accordingly.

Establishing a Human Chorionic Gonadotropin Cutoff to Guide Methotrexate Treatment of Ectopic Pregnancy: A Systematic Review

Methotrexate is an established alternative to surgery for treating ectopic pregnancy. While lower levels of human chorionic gonadotropin (hCG) correlate with a decreased risk of treatment failure, there is as yet no agreement on an absolute hCG level that would be a relative contraindication to methotrexate therapy. The authors undertook a systematic MEDLINE search and encountered 5 observational studies, totaling 503 women, that purportedly documented increasing failure rates in conjunction with increasing hCG levels. All of these studies followed a single-dose methotrexate protocol. Failure rates increased with higher hCG levels, and a substantial, statistically significant increase in failures was evident when comparing patients whose initial hCG levels exceeded 5000 mIU/mL with those having lower baseline levels. The odds ratio (OR) was 5.45, with a 95% confidence interval (CI) of 3.04-9.78. Women whose initial serum hCG level ranged from 5000 to 9999 mIU/mL had a significantly higher failure rate than those whose initial serum concentrations were 2000-4999 mIU/mL (OR, 3.76; 95% CI, 1.16-12.33). Another way to express this is that, for every 10 treatments there will be 1 more failure if the serum hCG is 5000-9999 mIU/mL than if it is 2000-4999 mIU/mL. The difference in rates approximates 10%. There is little difference in failure rates between groups with cutoff values greater than 5000 mIU/mL because overall failure rates are increased for both groups. These findings dictate a cautious approach when planning single-dose methotrexate treatment for ectopic pregnancy when the initial serum hCG level exceeds 5000 mIU/mL. It is not clear whether the use of a 2-dose or multidose protocol would yield different results.