Analysis of multistage in vitro fertilization data with mixed multilevel outcomes using joint modelling approaches

Summary In vitro fertilization comprises a sequence of interventions concerned with the creation and culture of embryos which are then transferred to the patient’s uterus. While the clinically important endpoint is birth, the responses to each stage of treatment contain additional information about the reasons for success or failure. Joint analysis of the sequential responses is complicated by mixed outcome types defined at two levels (patient and embryo). We develop three methods for multistage analysis based on joining submodels for the different responses using latent variables and entering outcome variables as covariates for downstream responses. An application to routinely collected data is presented, and the strengths and limitations of each method are discussed.