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

Advanced Access publication on May 7, 2014Non-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.A.W. Horne, M.M. Skubisz, S. Tong, W.C. Duncan, P. Neil, E.M.Wallace, and T.G. John

The health and educational costs of preterm birth to 18 years of age in Australia

Background: Preterm birth is the greatest cause of death up to five years of age and an im-portant contributor to lifelong disability. There is increasing evidence that a meaningful pro-portion of early births may be prevented, but widespread introduction of effective preventive strategies will require financial support.Aims: This study estimated the economic cost to the Australian government of preterm birth, up to 18 years of age.Materials and Methods: A decision-analytic model was developed to estimate the costs of preterm birth in Australia for a hypothetical cohort of 314 814 children, the number of live births in 2016. Costs to Australia’s eight jurisdictions included medical expenditures and ad-ditional costs to educational services.Results: The total cost of preterm birth to the Australian government associated with the an-nual cohort was estimated at $1.413 billion (95% CI 1047-1781). Two-thirds of the costs were borne by healthcare services during the newborn period and one-quarter of the costs by educational services providing special assistance. For each child, the costs were highest for those born at the earliest survivable gestational age, but the larger numbers of children born at later gestational ages contributed heavily to the overall economic burden.Conclusion: Preterm birth leaves many people with lifelong disabilities and generates a sig-nificant economic burden to society. The costs extend beyond those to the healthcare system and include additional educational needs. Assessments of economic costs should inform eco-nomic evaluations of interventions aimed at the prevention or treatment of preterm birth.John P. Newnham, Chris Schilling, Stavros Petrou, Jonathan M Morris, Euan M. Wallace, Kiarna Brown ... et al