Which protocol is better for treatment of ectopic pregnancy by methotrexate? Single-dose or multiple-dose

Khani, Behnaz; Behnamfar, Fariba; Taghiyar, Leila

doi:10.4103/abr.abr_5_20

Cited by 6 publications

(16 citation statements)

References 13 publications

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“…MTX is a folic acid analog that remarkably and persistently inhibits DHFR, and consequently decreases the production of thymidylate and DNA. LD-MTX can interfere with the DNA synthesis and inhibit proliferation of trophoblasts, preventing embryonic development, and it may lead to absorption ( 1 , 16 ). To date, only eight cases, including the present one, of single-dose LD-MTX protocols that induced serious adverse toxic effects on patients with EP have been reported ( Table 2 ) ( 10 , 19 – 24 ).…”

Section: Discussionmentioning

confidence: 99%

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Severe Adverse Toxic Effects of Low-Dose Methotrexate Treatment on an Ectopic Pregnancy Patient With Methylenetetrahydrofolate Reductase Mutations: A Case Report

Wang

Liang

et al. 2021

Front. Med.

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Background: Low-dose methylenetetrahydrofolate (LD-MTX) has been widely used for the treatment of the ectopic pregnancy (EP) for many decades, and related severe adverse toxic effects are rare. Current studies have shown that the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene can decrease the MTX clearance, leading to the metabolite accumulation. However, there is a lack of literature report on an MTHFR gene polymorphism associated with adverse toxic effects resulting from the use of LD-MTX in an EP.Case Presentation: We report a rare case of a 38-year-old female who developed persistent fever, grade IV myelosuppression, skin lesions, mucositis, and liver injury after single dose of LDMTX to treat EP. The personalized genetic testing showed that MTHFR TT (677C>T) and MTHFR AA (1298A>C) were detected. Gradually, the symptoms improved after calcium leucovorin (CF) rescue, continuous renal replacement therapy (CRRT), promoting blood system regeneration, and multiple supportive treatments.Conclusion: This is the first report on the serious adverse toxic effects of LD-MTX on an EP patient with MTHFR mutations. We aim to alert obstetricians and gynecologists to this rare condition. The unexpected life-threatening toxicity with LD-MTX should be highly considered and recognized early. In particular, some easily overlooked gastrointestinal, skin, and mucosal symptoms occur earlier than severe myelosuppression. When toxic effects are suspected, detecting the polymorphisms of an MTHFR gene and monitoring MTX concentration in blood could assist us to formulate individualized and active treatments.

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Section: Discussionmentioning

confidence: 99%

“…Methotrexate (MTX) is an antagonist of folic acid, which inhibits dihydrofolate reductase (DHFR) and prevents the proliferation of trophoblasts ( 1 ). MTX was first reported to treat ectopic pregnancy (EP) in 1982 ( 2 ).…”

Section: Introductionmentioning

confidence: 99%

Severe Adverse Toxic Effects of Low-Dose Methotrexate Treatment on an Ectopic Pregnancy Patient With Methylenetetrahydrofolate Reductase Mutations: A Case Report

Wang

Liang

et al. 2021

Front. Med.

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“…Up to four doses may be given to one patient, but not all four doses have to be given [ 19 ]. With multiple doses of MTX for interstitial pregnancy, success rates of 66 to 100 percent have been reported [ 10 , 20 ]. In 2017, Yang et al [ 21 ] published a systematic review and meta-analysis study for comparison of multiple-dose and double-dose versus single-dose administration of MTX for the treatment of EP.…”

Section: Discussionmentioning

confidence: 99%

Interstitial Ectopic Pregnancy: The Role of Mifepristone in the Medical Treatment

Stabile

Romano

Zinicola

et al. 2021

IJERPH

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Interstitial pregnancy is defined as the presence of a gestational sac in the most proximal section of the fallopian tube. Management of interstitial pregnancy remains a debated topic. Depending on hemodynamic stability, size of pregnancy, depth of surrounding myometrium, and desires for future fertility, interstitial pregnancy can be managed medically or surgically. We reviewed the literature in December 2020 using keywords “interstitial pregnancy”, “medical treatment”, “methotrexate”, and “mifepristone”. Articles published from January 1991 until 2020 were obtained from databases EMBASE, SCOPUS, and PUBMED. We describe the case of a patient with an interstitial pregnancy that was managed with a total medical approach in August 2020 at Burlo Garofolo Hospital. The patient was asymptomatic and hemodynamically stable, with a high level of serum β-hCG (22,272 mUi/mL). We used the combination of methotrexate (MTX) and mifepristone. Medical therapy was effective leading to interstitial pregnancy resolution in 51 days without collateral effects for the patient. We found seven previous cases reported in the literature. Our purpose is to underline the efficacy of medical therapy with systemic multidose MTX associated with a single oral dose of mifepristone and also folinic acid when is present a viable fetus and a high serum β-hCG level.

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“…7,9 Once opted for pharmacological treatment, there are some validated protocols for the administration of methotrexate, the most used being the short and long protocols. 12 The short protocol is the most used worldwide and consists of administering a single dose of 50 mg/m 2 , which can be repeated in a week, if necessary. In this protocol, β-hCG monitoring occurs on the day of treatment, day 4, and day 7, with the second dose of methotrexate being performed if gonadotropin levels do not drop by 15% between days 4 and 7.…”

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confidence: 99%

Adaptation of a Brazilian university hospital to clinical treatment of ectopic pregnancy: Lessons learned over 17 years

Tavares

Delfino

Ignarro

et al. 2023

Intl J Gynecology & Obste

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ObjectiveTo describe and compare the annual success rates of medical treatment in the analyzed period and to evaluate the associated factors.MethodsRetrospective study with 158 women with tubal pregnancy followed up over 17 years. Statistical analysis was performed using the Cochran‐Armitage test, the χ2 test, Mann–Whitney test, and multiple logistic regression.ResultsThe success rate was 47.4%. There was a trend of significant change in the success rate of clinical treatment over time (Z = 2.01, P = 0.044); it was associated to undergoing treatment between 2012 and 2017 (P = 0.028), the absence of abdominal pain (P = 0.020), receiving a higher dose of methotrexate (P < 0.001), and less time hospitalized (P < 0.001). In the final statistical model, we observed that receiving a higher dose of methotrexate (P = 0.025, odds ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.06), having a low serum β‐HCG concentration before treatment (P = 0.003, OR 0.87, 95% CI 0.79–0.95), and not having abdominal pain (P = 0.004, OR 4.26, 95% CI 1.61–11.28) were factors associated with a higher chance of successful clinical treatment for tubal pregnancy.ConclusionA greater chance of success was observed among women undergoing clinical treatment from 2012 onwards, who used higher doses of methotrexate, were asymptomatic at admission, and had low concentrations of β‐hCG.

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Which protocol is better for treatment of ectopic pregnancy by methotrexate? Single-dose or multiple-dose

Cited by 6 publications

References 13 publications

Severe Adverse Toxic Effects of Low-Dose Methotrexate Treatment on an Ectopic Pregnancy Patient With Methylenetetrahydrofolate Reductase Mutations: A Case Report

Severe Adverse Toxic Effects of Low-Dose Methotrexate Treatment on an Ectopic Pregnancy Patient With Methylenetetrahydrofolate Reductase Mutations: A Case Report

Interstitial Ectopic Pregnancy: The Role of Mifepristone in the Medical Treatment

Adaptation of a Brazilian university hospital to clinical treatment of ectopic pregnancy: Lessons learned over 17 years

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