Recurrence of gestational trophoblastic disease (GTD) following two attempts at in-vitro fertilization (IVF)/embryo transfer is reported in a childless couple after 17 years of unsuccessful trials of ovulation induction. The diagnosis of bilateral tubal obstruction was finally established, indicating IVF treatment. After the first IVF/embryo transfer treatment, the woman developed GTD and was treated with methotrexate. After a second IVF attempt, GTD was again diagnosed. This time there was no response to methotrexate, thus necessitating second-line chemotherapy. Etoposide, methotrexate, actinomycin D, cyclophosphamide, oncovine was used, and after only four treatment cycles the beta-human chorionic gonadotrophin (HCG) dropped to < 5 mIU/ml. After 26 months of follow-up, the beta-HCG continues to be undetectable. Preimplantation evaluation and ovum donation are described as measures to minimize the risk for GTD recurrence in a future IVF/embryo transfer.