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Evidence summaries

Success of Methotrexate Treatment of Ectopic Pregnancy and Serum Chorionic Gonadotropin Concentration

A high level of serum chorionic gonadotropin appears to predict poor success of methotrexate treatment. Level of evidence: "B"

A retrospective cohort study 4 included a total of 359 patients, with 268 (74.7%) succeeding with MTX and 91 (25.3%) required surgery. Specifically, 282 patients (78.6%) received 1-dose MTX, whereas 77 (21.4%) received 2-dose MTX. Gravidity, previous ectopic pregnancy, gestational age, pretreatment β-human chorionic gonadotropin (β-hCG) level, number of MTX treatments, and presence of a visible yolk sac in ultrasound were significant predictors. Higher gravidity (OR 1.25, 95% CI 1.01 to 1.54) and elevated pretreatment β-hCG levels (OR 1.00, 95% CI 1.0004 to 1.0008) were independent risk factors. Number of MTX treatments was a significant protective factor (OR 0.44, 95% CI 0.22 to 0.90).

A meta-analysis 5 included 7 RCTs with a total of 783 women. The 2-dose MTX protocol was associated with higher treatment success compared to the single-dose protocol (OR 1.84; 95% CI 1.13 to 3.00). The 2-dose protocol was more successful in women with high hCG (OR 3.23; 95% CI 1.53 to 6.84) and in women with a large adnexal mass (OR 2.93; 95% CI 1.23 to 6.9). The odds of side effects were higher in the 2-dose protocol.

Among 320 women in whom treatment was successful (91%) the mean serum chorionic gonadotropin concentration was 4 019 (SE 6 362), while it was 13 420 (SE 16 590) in those in whom the treatment was unsuccessful 1.

A systematic review 2 included 5 observational studies with a total of 503 women using single-dose methotrexate stratified by initial hCG concentration. Failure rates increase with increasing hCG levels. A significant increase in failure rates was seen when comparing patients with initial hCG levels over 5 000 mIU/mL with those with initial levels under 5 000 mIU/mL (odds ratio 5.45; 95% CI 3.04 to 9.78). The failure rate with hCG between 5 000 and 9 999 mIU/mL was significantly higher than with hCG between 2 000 and 4 999 mIU/mL (odds ratio 3.76; 95% CI 1.16 to 12.33).

A clinical trial 3 investigated pretreatment hCG cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy. 53 women received a single-dose regimen and 32 women received a multi-dose regimen. Medical treatment failure was defined as necessity of surgical treatment. Treatment success rate was 64.2% in the single-dose group and 71.9% in the multi-dose group (P>0.05). Pretreatment serum hCG titer was an independent prognostic factor for treatment success in each regimen. Serum hCG cutoff value to predict the treatment success was 3 026 IU/L in single-dose regimen group and 3 711 IU/L in multi-dose regimen group.

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    References

    • Lipscomb GH, McCord ML, Stovall TG, Huff G, Portera SG, Ling FW. Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies. N Engl J Med 1999 Dec 23;341(26):1974-8. [PubMed]
    • Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril 2007;87(3):481-4. [PubMed]
    • Kim J, Jung YM, Lee DY et al. Pretreatment serum human chorionic gonadotropin cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy. Obstet Gynecol Sci 2017;60(1):79-86. [PubMed]
    • Fu L, Liu X, Tian Z, et al. Risk factors for methotrexate treatment failure in tubal ectopic pregnancy: a retrospective cohort study. BMC Pregnancy Childbirth 2024;24(1):884. [PubMed]
    • Alur-Gupta S, Cooney LG, Senapati S, et al. Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis. Am J Obstet Gynecol 2019;221(2):95-108.e2. [PubMed]

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