Ectopic pregnancy (EP) is a pregnancy situated outside the uterine cavity (normal location). Early diagnosis of EP is possible with the advent of high resolution ultrasound and judicious use of serum Beta hCG levels (blood test), which in turn allow medical management in most cases. The choice of treatment should be guided by eligibility criteria and patient’s choice after discussing risks and benefits. Methotrexate (MTX) is the drug used for medical management of EP, sometimes in combination with mifepristone.

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Prerequisites for Medical Management

• Asymptomatic women with unruptured EP who are clinically stable, have normal baseline blood investigations (blood counts, liver and kidney function tests) and are willing for regular follow-up for 4-6 weeks, can be offered medical management.
• High serum Beta hCG levels (> 3500 mIU / ml), ectopic mass size > 3.5 cm and / or presence of cardiac activity in EP are relative contra indications to medical management.
• It should not be offered to those with significant bleeding into the abdomen or those with a coexisting viable intrauterine pregnancy.

Methotrexate Administration

Two protocols are currently used for medical treatment of EP : “Single Dose” MTX therapy at a dose of 50mg/m2 of body surface area and “Multidose” regimen consisting of 1mg / kg of MTX alternating with 0.1mg / kg of leucovorin for upto 4 doses of each agent. Both regimens are found to be effective.

• MTX can be given on Out Patient basis and intramuscular administration is the preferred route.
• Multidose regimen is preferred in women with high serum Beta hCG levels or those with presence of cardiac activity on ultrasound. In the single dose regimen, further doses of MTX may be repeated (upto a maximum of 3) if there is an inadequate response (<15% drop in serum Beta hCG).
• In the single dose regimen, further doses of MTX may be repeated (upto a maximum of 3) if there is an inadequate response (<15% drop in serum Beta hCG).

Laparoscopy is indicated if :

• Severe abdominal pain or signs suggestive of tubal rupture develop.
• There is no satisfactory drop in serum Beta hCG levels even after 3 doses in the single dose regimen or 4 doses in multidose regimen.

Anti D:

Regardless of the method of treatment Anti D should be given to all Rh negative women who have an EP.

Patient Should Be Advised To

• Avoid sexual intercourse until Beta hCG is <10 mIU / ml.
• Avoid pregnancy for three months after MTX injection, due to the theoretical risk of birth defects with MTX.
• Avoid sun exposure to limit risk of MTX dermatitis.
• Avoid foods and vitamins containing folic acid.

Post Treatment Management

Beta hCG  — Serial serum Beta hCG levels need to be checked on days 4 and 7 after MTX.

• If there is >15% decrease between days 4 and 7, weekly follow up is advised until Beta hCG is <10 mIU / mL.
• If <15% decrease is noted by day 7, 2nd dose of MTX is advised.
• In multidose regimen, serum Beta hCG levels are checked every 48 hours till significant decrease is noted and weekly thereafter.

Ultrasound — It is generally not repeated except to evaluate severe pain or suspected rupture or for patients with cardiac activity in the EP.

After completion of treatment, an ultrasound is advised to check for resolution of the EP which may take upto 3 months at times.

Efficacy

• Overall success of medical management is 88 – 90%.
• Around 14% of patients require a 2nd dose and less than 1% of women require more than 2 doses of MTX.

Side Effects

Drug related

Adverse reactions to MTX are usually mild and self-limited. Approximately 30% of patients in the single dose protocol will experience side effects, the most common are mouth ulcers and conjunctivitis.

Separation pain

Up to 75% of patients may complain of pain between days 2-7 after receiving the medication. This pain is usually mild and can be managed with paracetamol. Women with severe pain require further evaluation to rule out rupture of EP and the need for surgery.

Subsequent Reproductive Performance

• There is no evidence of adverse effects of MTX treatment on future pregnancies.
• Studies have shown a subsequent intra uterine pregnancy rate of 60-90%.
• The incidence of recurrent EP is approximately 7-15%.
• Women should be instructed to undergo an early ultrasound evaluation in subsequent pregnancies to confirm normal intrauterine location.