Combination gefitinib and methotrexate treatment for non-tubal ectopic pregnancies: a case series.

Non-tubal ectopic pregnancies are a rare subgroup of ectopic pregnancies implanted at sites other than the Fallopian tube. Mortality from non-tubal ectopic pregnancies is higher compared with that for tubal ectopic pregnancies, and they are becoming more common, partly due to the rising incidence of Caesarean sections and use of assisted reproductive technologies. Non-tubal ectopic pregnancies can be especially difficult to treat. Surgical treatment is complex, and follow-up after medical treatment is usually protracted. There is therefore a need for more effective medical therapies to resolve non-tubal ectopic pregnancies and reduce operative intervention. We have recently reported successful use of combination gefitinib (an orally available epidermal growth factor receptor inhibitor) and methotrexate for treatment of tubal pregnancies. To our knowledge, this combination has not been used to treat non-tubal pregnancies. Here we report the use of combination gefitinib and methotrexate to treat eight women with stable, non-tubal ectopic pregnancies at two tertiary academic teaching hospitals (Edinburgh, UK and Melbourne, Australia); five interstitial and three Caesarean section scar ectopic pregnancies. Pretreatment serum hCG levels ranged from 2458 to 48 550 IU/l, and six women had pretreatment hCG levels >5000 IU/l. The women were co-administered 1-2 doses of i.m. methotrexate (50 mg/m² on Day 1, ± Day 4 or Day 7) with seven once daily doses of oral gefitinib (250 mg). The women were monitored until complete resolution of the ectopic pregnancy, defined as a serum hCG <15 IU/l. Time to resolution (days from first methotrexate dose until serum hCG <15 IU/l), safety and tolerability, complication rates and subsequent fertility outcomes were also recorded. All eight women were successfully treated with combination gefitinib and methotrexate. The most common side effects were transient acne/rash and diarrhoea, known side effects of gefitinib. All women promptly resumed menstruation and importantly, three women subsequently conceived spontaneously. Two have delivered a healthy infant at term and the third is currently in her second trimester of pregnancy. Hence, our case series supports a future clinical trial to determine the efficacy of combination gefitinib and methotrexate to treat non-tubal ectopic pregnancies.

Decline in ßhCG levels between days 0 and 4 after a single dose of methotrexate for ectopic pregnancy predicts treatment success: a retrospective cohort study.

In current protocols for the medical management of ectopic pregnancies, the first indication of treatment response is obtained no sooner than day 7. We examined whether human chorionic gonadotrophin (ßhCG) trends between days 0 and 4 after methotrexate provide an earlier indication of the likely outcome. Of 33 patients where serum ßhCG dropped between days 0 and 4 after methotrexate, the ectopic pregnancy was resolved in 88% of cases without further treatment. Of 12 women where serum ßhCG rose between days 0 and 4, only 42% had treatment success. A fall in ßhCG between days 0 and 4 after treatment with methotrexate for ectopic pregnancy predicts a high likelihood of treatment success.