Factors determining success of the chronically instrumented unanesthetized fetal sheep model of human development: a retrospective cohort study

Aim Chronically instrumented non-anesthetized fetal sheep (CINAFS) have been the mainstay model of human fetal development for 60 years. As a large “two for one” animal model, with instrumentation of the ewe and her fetus, the model poses challenges to implement de novo and to maintain overtime at the highest standards of operating procedures to ensure its ongoing performance. A common, yet conventionally underreported issue researchers face is the rate of animal loss. Here, we investigate what determines the success of the pregnant sheep model. Methods We conducted a retrospective cohort study consisting of 82 experiments spanning the course of six years. Our team identified ten variables that we anticipated were likely to influence the experimental outcome, such as the time of year, animal size, and surgical complexity. Results The single variable identified in this study as determining the successful outcome of the experiments is the experience level of the team. Conclusion The CINAFS model offers enormous potential to further our understanding of human fetal development and to create interventional technologies. However, to improve the outcomes of CINAFS models, improved communication and training are needed. We discuss the implications of our findings for the successful implementation of this challenging yet scientifically advantageous animal model of human physiology. Key points The fetal sheep model closely mirrors the physiology of human fetal development In addition to its high translational potential, this model is known to have some generally not reported rate of experimental failure We show that factors such as animal characteristics & surgical complexity do not influence the experimental outcomes Instead, the key factor in model experimental success is the level of the research team’s experience The key factors to improve the animal model outcomes are an intra- and inter-team communication