A randomised phase III study to evaluate the effects of methotrexate in the treatment of women with an ectopic pregnancy to prevent the need for surgical intervention.

Method of Study Day of Presentation • Diagnosis of tubal ectopic pregnancy on TVS • Serum hCG, full blood count (FBC), group and save (G&S), liver and renal function tests • Providing patient fulfils above criteria, for possible inclusion in the study • Information leaflets given and advised to return in 48 hours for repeat hCG 48 hours later • If still asymptomatic and fulfilling the above criteria for possible participation in the study • If patient agrees to participate in study, consent form to be signed • Repeat hCG, FBC, liver and renal function tests to be taken. • If the hCG has decreased over the 48 hours for randomisation to either expectant (‘wait and see’) management or medical management in the form of intramuscular methotrexate • If the hCG has increased over the 48 hours for randomisation to either medical management in the form of methotrexate or surgery Medical Management • On this second visit intramuscular methotrexate will be given at a dose of 50mg/m2 • Repeat visits will then be required on days 3,4,5 and day 7 post methotrexate to measure the serum hCG. In addition on day 7 FBC, liver and renal function tests will be checked. (Day 1 = day of methotrexate) • If the hCG decreases by more than 15 % between days 4 and 7, the hCG will then be checked on a weekly basis until less than 15 IU/L • If it does not decrease by more than 15 % the woman will be rescanned and provided she is still asymptomatic and there are no changes on TVS, a second dose of methotrexate will be given. She will then be followed up with the same blood tests on days 3,4,5 and 7 post the second injection. • Regardless of the hCG change, if at any point the woman becomes symptomatic of there are any changes on USS such as haemoperitoneum, fetal cardiac activity or an increase in the size of the ectopic mass, she will be assessed with regard to laparoscopy and subsequent surgical treatment. Expectant Management • Blood tests to measure hCG will continue to be repeated every 48 hours, as long as they are not increasing until the hCG decrease is more than 15%. • Then blood tests will be repeated weekly until the levels are less than 15 IU/L • If at any point the woman becomes symptomatic of the hCG is increasing she will be assessed to see whether or not she should receive methotrexate and be followed up as above, or should undergo surgery. Surgical Management • In the majority of cases surgery will be laparoscopic, but occasionally a laparotomy will be required • If a laparoscopy is performed this will probably be done as a day case and therefore an over night stay avoided. • Either a salpingectomy or salpingostomy will be performed depending on the findings at the time. • Serial hCG follow up will be needed if a salpingostomy is performed or the ectopic pregnancy is ruptured. Levels will be taken weekly until less than 15 IU/l. If the levels plateau, methotrexate may need to be given. Subsequent Follow Up • Those treated surgically will be seen in clinic 2 weeks after the operation • Those treated expectantly or medically will be seen at 3 months