This chapter discusses the outcome of in vitro fertilization (IVF) in medically complicated patients. A confounding factor for IVF pregnancies is the increased number of multiple pregnancies and the relatively increased number of high-risk pregnancies among women with chronic medical problems. Cancer patients present particular challenges to the IVF unit. Standard IVF protocols are used for controlled ovarian hyperstimulation in human immunodeficiency virus (HIV) discordant couples. The main concerns about IVF and malignant disease relate to the issue of the potential delay in the starting of the patient's chemotherapy or of any possible effect of hormonal changes on the cancer. Obesity might affect the outcome of IVF and pregnancy, but with careful management, a good outcome can be achieved. It has been suggested that systemic lupus erythematosus (SLE) may reduce the success of IVF-ET. The presence of antinuclear antibodies may reduce the implantation rate in IVF patients.