[CG] Ectopic pregnancy, medical management

Please report any inaccuracies or issues with this guideline using our online form


  1. Antimetabolite and antifolate drug which is an established, effective and safe treatment for unruptured ectopic pregnancy and treatment of PUL.
  2. Success rates are around 80-90%.
  3. Careful patient selection is paramount- consultant review is required.
  4. Avoid aspirin or anti inflammatory drugs for 1 week after administration.
  5. Avoid alcohol, vitamins containing folic acid, intercourse, and travel out with the local area until follow up is complete.
  6. The vast majority of patients who have methotrexate will go on to have a subsequent intra-uterine pregnancy.

Patient selection

  1. Diagnosis of ectopic pregnancy or PUL confirmed according to EPAS guidelines.
  2. Patient clinically stable with minimal or no symptoms.
  3. No contra-indications to medical management.
  4. Patient fully counselled regarding treatment options and wishes medical management.
  5. Patient is able and willing to comply with follow up for several weeks - the average follow up time is 35 days.
  6. Patient agrees to avoid pregnancy until follow - up complete and three months after methotrexate.

Contra-indications to medical management

  1. Fetal cardiac activity.
  2. Concurrent intrauterine pregnancy (heterotopic pregnancy).
  3. Significant free intraperitoneal fluid.
  4. Serum HCG≥ 5000 iu/l.
  5. Abnormal renal or hepatic function- discuss with consultant if deranged.
  6. Adnexal mass ≥ 4 cm.
  7. Hb ≤ 100g/l, WCC≤ 2 x 109/l , platelets ≤100 x 10 9/ l
  8. Immunodeficiency.
  9. Patient currently breast feeding.
  10. Patient unwilling to avoid pregnancy for 3 months

Adverse effects

Most side effects are usually mild:

  • Nausea, diarrhoea, stomatitis.

More serious side effects are rare:

  • Impaired liver function, bone marrow suppression- usually reversible.

Abdominal pain occurs in about 75% of patients 3-7 days after methotrexate. This “separation pain” can be difficult to distinguish from pain due to rupture. If patient presents with concerning symptoms, carry out ultrasound to look for free fluid +/or admit for observation and senior review.

There is a 7% risk of tubal rupture following methotrexate.


Pre- treatment Investigations

  1. Serum HCG
  2. FBC, U+E, LFTs, blood group
  3. Height and weight. Calculate Surface Area-copy and paste the following into a web browser:

    (use the Dubois formula, weight in kg and height in centimetres)

  4. Offer Chlamydia screening.
  5. Pharmacy prescription to be completed by senior medical staff.

Treatment Schedule

Day 1. Methotrexate administration day

  1. Ensure patient has had appropriate counselling and information sheet.
  2. Ensure consent form signed.
  3. Ensure patient contact details are clearly documented in notes.
  4. Ensure patient has EPAS contact numbers and gynaecology ward number for out- of -hours advice
  5. Inform GP of diagnosis and treatment- see GP information leaflet.
  6. Administer methotrexate 50 mg/m2  IM-see methotrexate prescription form for dose banding according to surface area.

Day 4. EPAS Review

  1. Check serum HCG

Day 7. EPAS Review

  1. Check serum HCG
  2. If HCG on day 7 has fallen by 15% or more from day 4 levels, check HCG weekly until < 5iu/l.
  3. If HCG has not fallen by at least 15%, discuss with senior medical staff. In carefully selected cases, it may be appropriate to repeat HCG levels on day 10.
  4. If HCG has risen, refer to senior medical staff to discuss option of laparoscopy or a second dose of methotrexate.
  5. Approximately 15% of women will require a second dose of methotrexate.
  6. Very rarely, a third dose may be appropriate- this must be a consultant decision.

Second Dose of Methotrexate

  1. Ensure treatment criteria still fulfilled and discuss case with Consultant
  2. Transvaginal scan.
  3. FBC, U+E, LFT.

Further Follow up

  1. Check HCG levels weekly until <5iu/l
  2. If levels plateau or rise, discuss with senior medical staff
  3. Discharge patient when HCG < 5iu/l.


There are no absolute contra-indications to specific forms of contraception after an ectopic, other than usual cautions, but the use of a copper coil should be limited to patients for whom no other methods are suitable.

Subsequent pregnancies

Advise to attend EPAS early in next pregnancy to confirm location.

Appendix: Methotrexate for ectopic pregnancy

Last reviewed: 23 July 2021

Next review: 01 July 2024

Author(s): Lynne Thomson

Version: 4

Approved By: R. Jamieson, Clinical Director for Gynaecology

Document Id: 116