Journal of Womens Health, Issues and Care ISSN: 2325-9795

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Case Report, J Womens Health Issues Care Vol: 2 Issue: 4

Injection Methotrexate in the Management of Ectopic Pregnancy and Pregnancy of Unknown Location � An Audit of Cases at Princess Alexandra Hospital, UK

AR Bhoompally and Janaki Putran*
Department of Obstetrics and Gynaecology, Princess Alexandra Hospital, Harlow, Essex, UK
Corresponding author : Janaki Putran
Consultant in Obstetrics and Gynaecology, Princess Alexandra Hospital, Harlow, Essex, UK
Tel: 00 441279827107; Fax: 00 441279 827554
E-mail: [email protected]
Received: February 04, 2013 Accepted: June 13, 2013 Published: June 17, 2013
Citation: Bhoompally AR, Putran J (2013) Injection Methotrexate in the Management of Ectopic Pregnancy and Pregnancy of Unknown Location – An Audit of Cases at Princess Alexandra Hospital, UK. J Womens Health, Issues Care 2:4. doi:10.4172/2325-9795.1000111


Injection Methotrexate in the Management of Ectopic Pregnancy and Pregnancy of Unknown Location – An Audit of Cases at Princess Alexandra Hospital, UK

Ectopic pregnancy is usually treated with surgery. Injection methotrexate is a treatment option for ectopic pregnancy and for Pregnancy of Unknown Location. Meta-analysis of studies have not shown a statistical difference in the success rate or future pregnancy rate or recurrent ectopic pregnancy rate when comparing injection methotrexate with surgery.

Keywords: Methotrexate; Ectopic pregnancy; Laparoscopy


Methotrexate; Ectopic pregnancy; Laparoscopy


The management options for an ectopic pregnancy include surgery, medical or rarely expectant treatment. The most commonly used drug for a medical management of an ectopic pregnancy is methotrexate.
Pregnancy of unknown location is defined as a positive urine pregnancy test with the absence of either an intra uterine or extra uterine pregnancy on ultrasound scan [1]. Most cases of pregnancy of unknown location (PUL) resolve spontaneously over time. A few cases of PUL persist and injection methotrexate is a treatment option in such cases.
Methotrexate is an antimetabolite, which prevents the growth of rapidly dividing cells by interfering with DNA synthesis. For the treatment of ectopic pregnancy methotrexate is commonly given intramuscular as a single dose.
The pre-treatment serum beta human Chorionic Gonadotropin (Serum β-hcg) level is said to be the best predictor of the success of methotrexate treatment. Success rates are over 90% with appropriate patient selection [2]. The tube is conserved with an 80% chance of tubal patency. Subsequent fertility appears to be as good as conservative therapy (>70%) and the risk of recurrent ectopic is about 15%.
Meta analysis comparing surgery with systemic methotrexate show there is no statistical difference in the success rate, future pregnancy rate and recurrent ectopic pregnancy rate [3].
One important advantage of medical therapy is the potential for considerable savings in treatment costs. According to the National Institute for Health and Clinical Excellence, (NICE) Clinical Guidelines [3] injection methotrexate is the cheapest treatment option at £1432 followed by laparoscopic salpingectomy at £1608 and laparoscopic salpingotomy at £2205.
The disadvantages of methotrexate therapy are the risk of toxicity and the need for compliance in follow-up to ensure resolution of pregnancy. Abdominal pain is common in the first week following treatment with methotrexate.
Methotrexate is a known teratogen with an increased risk of skull and limb deformities in the fetus. Pregnancy must be avoided for three months. Patients are advised to take 5 mg folic acid during the pre-conception period and in early pregnancy.
Patients must avoid non steroidal anti inflammatory drugs, trimethoprim and folic acid during treatment.
The resolution time is much longer than in women who opt for surgical management of an ectopic pregnancy. Hence follow up and compliance is vital.

Materials and Methods

Case notes of patients who received injection methotrexate for either an ectopic pregnancy or a PUL between November 2010 and October 2012 in the Early Pregnancy Unit (EPU) at The Princess Alexandra Hospital, UK were reviewed.
The Royal College of Obstetricians and Gynecology (RCOG) guidelines on the use of injection methotrexate as outlined in Table 1 are followed in our Early Pregnancy Unit.
Table 1: RCOG Guidelines on use of Injection Methotrexate.
We gave a single dose of injection methotrexate intramuscular. The dose was calculated on the basis of the body surface area (height×weight) multiplied by 50 [4].
The injection was given in EPU as an outpatient procedure.
All women were counseled thoroughly. A checklist was used and written consent was taken before giving the injection methotrexate. Table 2 shows the checklist used. A signed copy of the checklist was given to the patient. Special emphasis was given on need for follow up, avoidance of alcohol and certain medication. The need to avoid pregnancy for 3 months was also discussed.
Table 2: Checklist for Injection Methotrexate.
All patients were followed up in EPU as outpatient with weekly monitoring of serum β-hcg levels. They were advised to come to Accident and Emergency if they had acute onset abdominal pain.
Serum β-hcg was measured on days 4, 7 and then weekly. A rise in serum β-hcg is not unusual on day 4 of the treatment. A failure of serum β-hcg to fall by 15% between days 4 and 7 was an indication for a second dose of injection methotrexate.
The women were followed up with weekly serum β-hcg levels till the level fell to below 20 IU/L.
We looked at the need for second dose of injection methotrexate, the need for emergency admission and laparoscopy. We also looked at the resolution time i.e. the time taken for the serum β-hcg level to fall below 20 IU/L. In some patients if the serum β-hcg level fell consistently the monitoring was stopped at slightly higher level.


Of the 21 women who were given injection methotrexate, 11 were for Pregnancy of Unknown Location, 9 were for an ectopic pregnancy and 1 was for a cornual pregnancy.
All women who were diagnosed as an ectopic pregnancy on ultrasound scan had an adnexal mass of less than 35 mm. except one patient whose adnaexal mass measured 45×41×35 mm. She declined laparoscopy and opted for injection methotrexate.
For the patient with the cornual ectopic pregnancy, even though the serum β-hcg level was greater than 3000 IU/L, injection methotrexate was considered to be a safer option than surgery.
In one patient the serum β-hcg was very high at 11653 IU/L, However, she was asymptomatic and having had a previous left salpingectomy for an ectopic pregnancy was very keen to try injection methotrexate.
Table 3 outlines the indication, serum β-hcg levels and ultrasound findings on the day of injection methotrexate.
Table 3: Indication for injection methotrexate.
Time to resolution
The time to resolution of the pregnancy was defined as the time interval between the day injection methotrexate (day 0) was given and the day serum β-hcg level fell below 20IU/L.
The range was between 7 and 56 days with most pregnancies resolving in 14 to 28 days (Table 4).
Table 4: Time to Resolution.
All levels of serum ß-hcg in IU/L
In one patient, monitoring was stopped at a slightly higher level at the patient’s request.
Need for laparoscopy or emergency admission
All patients were managed as outpatient from EPU.
One patient was admitted twice as an in-patient with lower abdominal pain. She was clinically stable and her serum β-hCG levels were dropping. A repeat ultrasound scan did not show any change from her initial scan. She was managed conservatively and sent home with codeine phosphate for pain relief. She was followed up in EPU and the pregnancy resolved in 21 days time.
Efficacy of methotrexate
Of the 21 cases we had over a two-year period, we had a 100% success rate. None of the patients needed emergency surgery. Though the initial serum β-hcg level as very high in one patient, the levels fell consistently and the pregnancy resolved in 56 days.
Need for second dose
A rise in serum β-hcg is not unusual on day 4 of the treatment. A failure of serum β-hcg to fall by 15% between days 4 and 7 was an indication for a second dose of injection methotrexate.
The serum β-hcg rose on day 4 of treatment in 6 patients. But the serum β-hcg fell by 15% or more by day 7 and none of our patients needed a second dose of injection methotrexate.


Injection methotrexate is a safe alternative to surgery for ectopic pregnancy. Sometimes it is the only option for unresolving PUL in carefully selected cases.


Carol Muir and Maricris Maghari, our EPU specialist nurses for their help and dedication to the above service.


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