Methotrexate treatment of very high ß-HCG ectopic pregnancy on previous cesarean scar: A case report.

Ectopic pregnancy in a previous caesarean scar is a rare, potentially life-threatening situation that can cause massive bleeding and uterine rupture. Clinical symptoms can range from vaginal bleeding with or without pain, to uterine rupture with hypovolemic shock. Early diagnosis is possible by ultrasound examination, and it is very important because it leads to prompt management, improving maternal morbidity and mortality as well as future fertility. The current case report refers to a G3P2 woman with a history of 2 previous caesarean deliveries, who was diagnosed with an ectopic pregnancy on the caesarean scar using ultrasonography. The patient was treated with methotrexate both systemic and into the sac, as well as with injection into the sac of 5mEq potassium chloride. The woman was followed up until measurements of serum ß-Human Chorionic Gonadotropin were within nonpregnant levels. There is no clear-cut best way to handle cesarean scar pregnancy. Pregnancy with a cesarean scar should be identified and treated as soon as possible in order to avoid serious problems and preserve fertility. However, even more advanced cesarean scar pregnancies can be managed conservatively at first, when a highly expertized team in a tertiary hospital is available.

Differences in Administration of Methotrexate and Impact on Outcome in Low-Risk Gestational Trophoblastic Neoplasia.

Methotrexate (MTX) is frequently used as first-line treatment for low-risk gestational trophoblastic neoplasia (GTN). Intravenous and intramuscular (im) routes of administration are the most common methods, although oral administration is used by some Scandinavian centers. The primary aim of this study was to assess the impact of form of administration (im/oral) on resistance to methotrexate (MTX-R) treatment in low-risk GTN. Secondary aims were time to hCG normalization, rates of toxicity-induced treatment switch, and rates of complete remission and recurrence. In total, 170 women treated at Karolinska University Hospital in Sweden and Aarhus University Hospital in Denmark between 1994 and 2018 were included, of whom 107 were given im and 63 oral MTX. MTX-R developed in 35% and 54% in the im and oral groups, respectively (p = 0.01). There was no difference in days to hCG normalization (42 vs. 41 days, p = 0.50) for MTX-sensitive women. Toxicity-induced treatment switch was only seen in the im group. Complete remission was obtained in 99.1% and 100% (p = 0.44), and recurrence rate within one year was 2.8% and 1.6% (p = 0.29). The form of administration of MTX had a significant impact on development of MTX-R and treatment-associated toxicity, but does not affect rates of complete remission, recurrence or survival.

Relationship Between Interleukin-6 -174G/C Genetic Variant and Efficacy of Methotrexate Treatment in Psoriatic Arthritis Patients.

INTRODUCTION: The purpose of the study was to investigate whether single-nucleotide polymorphisms (SNPs) IL-6 -174 G/C and IL-6R Asp358Ala are associated with susceptibility to psoriatic arthritis (PsA) or affect response to treatment with methotrexate (MTX). PATIENTS AND METHODS: Seventy-four patients diagnosed with PsA and qualified for MTX treatment were enrolled to the study. The control group consisted of 120 healthy individuals. Polymorphisms IL-6 -174 G/C and IL-6R Asp358Ala were genotyped using a polymerase chain reaction (PCR) amplification employing LightSNiP assays. RESULTS: A significant association between the IL-6 -174 CC genotype and an improved clinical outcome of MTX therapy was observed. A good response was more frequently observed among PsA patients bearing the IL-6 -174 CC genotype than patients with the GC or GG genotypes (P = 0.007). On the other hand, patients carrying the IL-6 -174 GC genotype less frequently responded to MTX treatment as compared to patients with other genotypes (P = 0.006). With respect to the IL-6R Asp358Ala SNP, there were no significant differences in genotype and allelic frequencies in relation to clinical outcome of MTX treatment. No association was found between the IL-6 -174 G/C or IL-6R Asp358Ala SNPs and PsA susceptibility. CONCLUSION: Results from this study provide evidence that the IL-6 -174 G/C polymorphism might influence efficacy of MTX treatment.

Selection and perception of methotrexate treatment information in people with rheumatoid arthritis.

OBJECTIVE: To determine beliefs about methotrexate (MTX) in patients with rheumatoid arthritis (RA) in relation to utilized information sources. METHODS: RA patients, who were current participants in the Australian national biologic registry, completed an online questionnaire regarding their use and views about MTX (N = 1010). Participants who used MTX were asked about which MTX information sources they consulted, and whether positive or negative views were obtained. The Beliefs about Medicine Questionnaire (BMQ), was used to measure patient beliefs about MTX. RESULTS: The survey response rate was 804/1010 (80%). MTX survey data were analyzed for 742 RA participants (mean age 59 years, 76% female, mean disease duration 19 years) who had used MTX, with 494/742 (67%) reporting current use. Participants consulted multiple information sources (median 3, interquartile range 1-5). Rheumatologists (98%), general practitioners (GPs) (55%), internet searches (39%), educational websites (38%), and pharmacists (37%) were the most common information sources utilized. Positive MTX information was most often obtained from rheumatologists (92%), GPs (66%), and educational websites (56%). Negative information was most often obtained from relatives, social media, internet chat rooms and friends. Information from rheumatologists was the most influential on favorable BMQ MTX-specific scores, whereas information from educational websites also affirmed the need for MTX. CONCLUSION: RA patients have significant concerns regarding MTX and consult a variety of sources for MTX information. However, the patient perception of this information varies widely. Rheumatologists and educational websites are the most important information sources in terms of a positive influence on the patient's perception of MTX.

A Novel Strategy for Treating Inflammatory Bowel Disease by Targeting Delivery of Methotrexate through Glucan Particles.

Therapy of inflammatory bowel disease (IBD) has been a difficult task in the medical field. There is a great clinical need for more effective treatments for IBD. Herein, a targeted oral delivery system of yeast glucan particles (YGPs) carrying a clinically used anti-inflammatory drug methotrexate (MTX) to the inflamed sites in IBD mice for therapy is reported. In the findings, MTX is effectively loaded into YGPs through re-precipitation followed by gelation reaction of alginate to obtain the composite YGPs/MTX, which are internalized into RAW264.7 macrophage cells through dectin-1 and CR3 receptors. Furthermore, YGPs/MTX can suppress the proliferation of macrophage cells efficiently, leading to down-regulation of pro-inflammatory cytokines induced by lipopolysaccharides. Additionally, YGPs accumulate in the inflammation site of colitis mice, enabling YGPs/MTX to target the inflammatory site, significantly improve the efficacy of MTX, and reduce the cytotoxicity of MTX. Therefore, the YGPs-based drug delivery system provides a new strategy for MTX application in the clinical treatment of IBD.

Successful management of a rudimentary uterine horn ectopic pregnancy by combining methotrexate and surgery: A case report.

Pregnancy in a non-communicating rudimentary uterine horn is rare but presents a significantly increased risk of maternal and foetal morbidity due to uterine rupture. We describe a case of rudimentary horn pregnancy diagnosed in the first trimester in an asymptomatic and haemodynamically stable woman. Medical termination of the pregnancy was performed with systemic and intrasacular methotrexate. Laparoscopic uterine horn excision was performed three months after termination. This case shows that early diagnosis of a rudimentary horn pregnancy is key to the successful management of this condition. Preoperative medical termination in an asymptomatic woman proved to be an effective and safe option that minimized surgical risks.

Significant increase in serum hCG levels following methotrexate therapy is associated with lower treatment success rates in ectopic pregnancy patients.

OBJECTIVE: To determine the association between early increase in the serum hCG levels (days 0-4) and treatment success rates following methotrexate therapy in ectopic pregnancy patients. STUDY DESIGN: A level II-2 case-control study of involving 140 patients treated with methotrexate for ectopic pregnancy at the gynecology department in a tertiary care hospital. RESULTS: A logistic regression model for the "failure of treatment" was fitted with serum hCG levels change between day 0 and day 4, patient age, pregnancy age at day-0, and day-0 ß-hCG level as predictors. The logistic regression analysis indicated that having more than 50% increase in the ß-hCG levels between days 0 and 4 significantly (P = 0.011) increases the risk of MTX treatment failure. CONCLUSION: The results of this study indicate that >50% increase in ß-hCG levels between days 0 and 4 significantly increases the risk of methotrexate treatment failure. This novel information could assist patients and physicians in making decisions regarding ectopic pregnancy treatment.

A risk prediction model for medical treatment failure in tubal pregnancy.

OBJECTIVE: Methotrexate is an alternative treatment for tubal pregnancy. However, despite initial treatment, ∼15% of women eventually require surgery. This study aimed to identify the risk factors for medical treatment failure in tubal pregnancy and apply them to a risk prediction model. STUDY DESIGN: This single-center retrospective cohort study included 123 participants initially treated medically for tubal pregnancy between January 2006 and December 2015. Logistic regression analysis was used to construct a risk prediction model (visually presented as a nomogram) for medical treatment failure. Model performance was assessed using discrimination and calibration. The medical treatment failure rate was 36.6%. The prediction model integrated the presence of a gestational sac, ectopic mass size, and follow-up ß-human chorionic gonadotropin levels above cut-off values on days 4 and 7. The model used the following cut-off values: increased ß-human chorionic gonadotropin levels by 1028.6 mIU/mL, 1.0457-fold higher than baseline level on day 4; and increased ß-human chorionic gonadotropin levels by 1233 mIU/mL, 1.3025-fold higher than baseline level on day 7. RESULTS: The corresponding areas under the receiver-operating characteristic curves were 0.8135 (95% confidence interval, 0.733-0.893) for the day 4 model and 0.8600 for the day 7 model (95% confidence interval, 0.788-0.932). Comparison of the day 4 and 7 models revealed no significant difference in their predictive abilities (P = 0.4318). CONCLUSIONS: This model identified a substantial proportion of the participants who experienced medical treatment failure for tubal pregnancy. It was visualized as a nomogram, facilitating clinical application.

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

OBJECTIVES: This 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 METHODS: A 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 ß-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. RESULTS: Data from 120 patients were analyzed: Group 1 (n = 92); Group 2 (n = 28). ß-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 ß-hCG levels were independent predictors of failure. CONCLUSION: Day (0-4) thresholds or newly defined day (4-7) thresholds were not more sensitive than the conventional day (4-7) criteria. Day (0-4) ß-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%.

Routine ß-Human Chorionic Gonadotropin Monitoring for Single-Dose Methotrexate Treatment in Ectopic Pregnancy.

STUDY OBJECTIVE: To evaluate an alternative monitoring protocol without day 4 ß-human chorionic gonadotropin (ß-hCG) measurement for predicting the need for a repeated methotrexate (MTX) dose in patients undergoing single-dose MTX therapy for ectopic pregnancy (EP). DESIGN: Single-center retrospective study (Canadian Task Force classification II-3). SETTING: University-affiliated hospital. PATIENTS: Included in the study were 184 EP patients treated with MTX between January 2009 and December 2016. INTERVENTIONS: Single-dose MTX treatment (50 mg/m2). MEASUREMENTS AND MAIN RESULTS: The patients were treated with repeated doses of MTX every 7 days, if necessary, according to Stovall's protocol, or with laparoscopic surgery in cases of tubal rupture. The success of a single-dose of MTX according to the alternative measure was defined as a >50% decrease in the ß-hCG level between days 1 and 7 in clinically stable patients. The sensitivity, specificity, false-negative rate, false-positive rate, and attributable risk of this new monitoring measure were calculated and compared with the traditional regimen. The new protocol had a sensitivity and specificity of 100% and 88.7%, respectively, for predicting a required second dose in patients whose day 1 ß-hCG levels were <2000 mIU/mL. For patients with day 1 ß-hCG level ≥2000 mIU/mL, both monitoring regimens had the same efficiency. CONCLUSIONS: The new monitoring model without the day 4 ß-hCG measurement may offer both patients and clinicians multiple options to monitor single-dose MTX therapy for selected EP patients, with a comparable clinical efficiency to Stovall's protocol and less expense and follow-up burden to patients.

Success rates of single-dose methotrexate and additional dose requirements among women with first and previous ectopic pregnancies.

OBJECTIVE: To compare the success of the single-dose methotrexate regimen and the requirement for a second or third dose of methotrexate between women with their first ectopic pregnancy (EP) and those with previous EP. METHODS: In a retrospective cohort study, data were analyzed from women treated for EP by single-dose methotrexate at a Turkish tertiary referral center between January 2010 and December 2013. Data were compared between women with at least one previous EP and those with their first EP. RESULTS: The success rate of the protocol in the first and previous EP groups was similar: 93.0% (320/344) and 87.3% (48/55), respectively. History of previous EP was not a predictor of treatment failure. However, the requirement for additional methotrexate doses was significantly higher in the previous EP group (16/48 [33.4%]) than in the first EP group (55/320 [17.2%]; P=0.03). Multivariate analysis showed that history of tubal surgery (P=0.006) and initial levels of the ß-subunit of human chorionic gonadotropin (P=0.001) were significant predictors of treatment failure. CONCLUSION: Although the single-dose regimen had similar success rates in the previous EP and first EP groups, additional doses of methotrexate were more frequently required in the previous EP group.

Effect of single-dose methotrexate on ovarian reserve in women with ectopic pregnancy.

OBJECTIVE: To evaluate ovarian reserve in women with ectopic pregnancy treated with single-dose systemic methotrexate in the early post-treatment period. DESIGN: Prospective study. SETTING: Women's health education and research hospital. PATIENT (S): Eighty-two patients with ectopic pregnancy and 80 healthy women in the same age group were included in the study. Of the 82 patients, 49 with ectopic pregnancy were treated with single-dose systemic methotrexate (MTX) and 33 were treated surgically with laparoscopy or laparotomy (salpingectomy or salpingostomy). INTERVENTION(S): Ovarian reserve testing. MAIN OUTCOME MEASURE(S): Basal FSH on the 3rd day of the menstrual cycle, E2, basal antral follicle count (AFC), and ovarian volume. RESULT(S): There were no differences among the groups in terms of basal FSH, E2, AFC, and ovarian volume. CONCLUSION(S): The single-dose MTX treatment had no effect on ovarian reserve in women with ectopic pregnancy as measured by the above-mentioned parameters.