Gravidity, beta-hCG level may predict methotrexate failure for ectopic pregnancy

Key takeaways:

• The overall failure rate of methotrexate was 25.3% for women with an ectopic pregnancy.
• Gravidity and elevated beta-human chorionic gonadotropin levels predicted methotrexate failure.

For women with an ectopic pregnancy, higher gravidity, elevated beta-human chorionic gonadotropin levels and number of drug doses were predictors of methotrexate treatment failure, researchers reported in BMC Pregnancy and Childbirth.

“The management of ectopic pregnancy includes expectant, medical and surgical management. Methotrexate is a safe, noninvasive and effective treatment option,” Linru Fu, MD, from the department of obstetrics and gynecology at Peking Union Medical College Hospital at the Chinese Academy of Medical Sciences and the Peking Union Medical College at the National Clinical Research Center for Obstetric & Gynecologic Diseases in Beijing, and colleagues wrote. “Previous studies have shown no significant differences between radical or conservative surgeries and methotrexate treatment in terms of subsequent live births and recurrent ectopic pregnancy and methotrexate is more cost-effective than conservative surgical interventions are. However, methotrexate treatment has a failure risk ranging from 10% to 36%, which raises concerns when this therapeutic option is selected.”

Fu and colleagues conducted a retrospective study with 359 women diagnosed with ectopic pregnancy at Peking Union Medical College Hospital between 2016 and 2022. Initially, all participants received methotrexate treatment with varied dosing intervals and protocols based on clinical practice. Researchers defined methotrexate treatment failure as the need for surgery after administration.

Overall, 78.6% of women received one methotrexate dose and 21.4% received two methotrexate doses; 25.3% of women experienced methotrexate treatment failure.

Gravidity, previous ectopic pregnancy, gestational age, beta-human chorionic gonadotropin (beta-hCG) level, number of methotrexate treatments and the presence of a visible yolk sac via ultrasound were all predictors of methotrexate treatment failure (P < .05 for all). In the multivariate analysis, researchers confirmed that higher gravidity (OR = 1.2487; 95% CI, 1.0103-1.5433; P = .04) and elevated hCG levels (OR = 1.0006; 95% CI, 1.0004-1.0008; P < .001) were independent risk factors for methotrexate treatment failure. Previous ectopic pregnancy, gestational age and visible yolk sac were no longer significant.

In addition, the number of methotrexate treatment doses was a protective factor in ectopic pregnancy (OR = 0.4409; 95% CI, 0.2153-0.9025; P = .025).

Researchers used the findings to develop a nomogram incorporating predictive risk factors for methotrexate treatment failure including gravidity, previous ectopic pregnancy, gestational age, pretreatment beta-hCG level, number of methotrexate treatments and visible yolk sac. Researchers estimated the probability of methotrexate treatment failure by combining each variable’s score and projecting the total score onto the lower total point scale. According to the researchers, the nomogram had an area under the curve of 0.738, indicating good predictive performance.

“The nomogram developed herein serves as a valuable tool for predicting treatment outcomes, enhancing the precision of patient management,” the researchers wrote. “However, the limitations of this study, including its retrospective and single-center design, suggest that future research should focus on optimizing methotrexate dosing regimens based on prospective multicenter studies, and it is also important to elucidate the underlying mechanisms of treatment failure to further improve patient outcomes.”