Ectopic Pregnancy: A Clinical Casebook

8. Compliance with Methotrexate Treatment for Ectopic Pregnancy

Ishai Levin  and Benny Almog 


Lis Maternity Hospital, Tel Aviv Sourasky Medical Center Affiliated to Sackler School of Medicine, Tel Aviv University, 6 Weizmann St., 69234 Tel Aviv, Israel

Ishai Levin (Corresponding author)


Benny Almog



Patient complianceComplianceEctopic pregnancyRuptured ectopic pregnancyTubal rupture

Case Presentation

A 29-year-old homeless woman presented to the emergency department with left lower quadrant abdominal pain. Her medical history revealed previous admissions for sexually transmitted disease and pelvic inflammatory disease (PID) treated with antibiotics. She could not remember the date of her last menstrual period, but assumed that it was a month ago. Upon admission, she was hemodynamically stable with mild tenderness in her left lower quadrant. The serum Beta-human Chorionic Gonadotrophin (hCG) was1200 IU/L. Transvaginal ultrasound examination showed a 17 mm mass typical of an ectopic pregnancy on the left adnexa. The consulting gynecologist decided to treat the patient with a single dose of methotrexate (50 mg/m2 body weight) intramuscularly.

My Management




Assessment and Diagnosis

The patient is at high risk for ectopic pregnancy due to her sexually transmitted disease and PID [1]. The history, symptoms, physical exam as well as imaging studies are suggestive of an ectopic pregnancy and the diagnosis can be safely made. Medical treatment with methotrexate would result in high success rates (93 %) due to a relatively low level of beta-hCG [2]. One of the most important aspects of methotrexate treatment is the ability to follow the patient. Persistent ectopic pregnancy or tubal rupture can occur. Historically, up to 24 % of patients with persistent ectopic pregnancies have experienced rupture of the ectopic mass necessitating urgent treatment [3]. In a large number of patients with ectopic pregnancy who were hemodynamically stable and treated with a single dose of methotrexate, the failure rate was 13 % and an additional 14 % required a second dose of methotrexate [4]. The failure rate correlates with levels of beta-hCG [25].

The patient described was an underprivileged individual. Her willingness to seek medical care was questionable and her compliance for follow-up had to be carefully assessed. Studies examining compliance with methotrexate protocols demonstrate that underprivileged inner-city populations do not comply with treatment satisfactorily. Watters et al. demonstrated that only 14.8 % of patients treated with methotrexate adhered to the protocol and concluded that patients’ follow-up and compliance rates were poor in the disadvantaged population of Cook county hospital [6]. Similarly, Carter et al. demonstrated 18.3 % compliance for follow-up among medically treated patients [7]. Dueñas-Garcia et al. had an 87.9 % success rate for methotrexate therapy but only 10.1 % of their patients were fully compliant with therapy [8]. In an inner-city hospital in Philadelphia, only 19.7 % of patients were fully compliant with therapy. It increased to 45.5 % after numerous reminders by telephone or letters [9].

The ACOG Practice Bulletin defines patients with the questionable ability to return to all follow-up visits as poor candidates for medical therapy. Patients who cannot return for follow-up after methotrexate administration should not be treated medically [10].

The compliance of adolescents receiving medical therapy for ectopic pregnancy was found to be similar to that of adults [11]. A study conducted among Canadian physicians demonstrated that about 50 % of them would probably withhold methotrexate treatment to adolescents who have a history of noncompliance with oral contraceptives or suffer from substance abuse [12].


The main concern in treating this patient is compliance . It is questionable whether the patient will adhere to the treatment protocol. With serum beta-hCG levels of 1200 IU/mL, the chance of treatment success is over 90 % [2413], but continued follow-up with serial serum hCG monitoring is mandatory. Our patient is a poor candidate for medical therapy with methotrexate. A comprehensive “team” discussion involving social workers should be carried out with the patient. A decision regarding therapy should be taken after assessing the risks and benefits.

Our patient will benefit more from surgery and salpingectomy . The benefits of a minimally invasive surgical procedure in this particular patient are higher than the risks of rupture or persistent trophoblast that can be life-threatening.


Considering all the factors stated above, the patient was treated surgically. Laparoscopy revealed a nonruptured left ectopic ampullary pregnancy and a left salpingectomy was carried out. The patient recovered fully and was discharged the following day.

Clinical Pearls/Pitfalls

·               One in four patients with persistent ectopic pregnancies might eventually have tubal rupture.

·               Compliance with follow-up treatment among underprivileged inner-city inhabitants is low (approximately 20 %).

·               A careful assessment regarding the patients’ ability to comply with treatment protocol before deciding on the treatment should be performed.

·               Poorly compliant patients should be treated surgically(Table 8.1).

Table 8.1

Compliance rate for methotrexate therapy in inner-city populations

Author (Ref)

Watters et al. [6]

Carter et al. [7]

Duenas-Garcia et al. [8]

Jaspan et al. [9]


Cook Country Hospital, Northwestern University, Chicago, IL

Medstar Washington Hospital Center, Washington DC

Bronx Lebanon Hospital Center, New-York City, NY

Albert Einstein Medical Center, Philadelphia, PA

Number of patients





Patients completing follow-up (%)





Successful medical therapy (%)







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Seifer DB. Persistent ectopic pregnancy: an argument for heightened vigilance and patient compliance. Fertil Steril. 1997;68(3):402–4.CrossRefPubMed


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Lipscomb GH. Medical therapy for ectopic pregnancy. Semin Reprod Med. 2007;25(2):93–8.CrossRefPubMed


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McCord ML, et al. Methotrexate therapy for ectopic pregnancy in adolescents. J Pediatr Adolesc Gynecol. 1996;9(2):71–3.CrossRefPubMed


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Lipscomb GH, et al. Comparison of multidose and single-dose methotrexate protocols for the treatment of ectopic pregnancy. Am J Obstet Gynecol. 2005;192(6):1844–7 (discussion 1847–8).CrossRefPubMed