Unsettled knowledge as to whether scrapie transmits prenatally in sheep and goats and transmits by semen and preimplantation embryos has a potential to compromise measures for controlling, preventing and eliminating the disease. The remedy may be analysis according to a systematic review, allowing comprehensive and accessible treatment of evidence and reasoning, clarifying the issue and specifying the uncertainties. Systematic reviews have clearly formulated questions, can identify relevant studies and appraise their quality and can summarise evidence and reasoning with an explicit methodology. The present venture lays a foundation for a possible systematic review and applies three lines of evidence and reasoning to two questions. The first question is whether scrapie transmits prenatally in sheep and goats. It leads to the second question, which concerns the sanitary safety of artificial breeding technologies, and is whether scrapie transmits in sheep and goats by means of semen and washed or unwashed in vivo derived embryos. The three lines of evidence derive from epidemiological, field and clinical studies, experimentation, and causal reasoning, where inferences are made from the body of scientific knowledge and an understanding of animal structure and function. Evidence from epidemiological studies allow a conclusion that scrapie transmits prenatally and that semen and embryos are presumptive hazards for the transmission of scrapie. Evidence from experimentation confirms that semen and washed or unwashed in vivo derived embryos are hazards for the transmission of scrapie. Evidence from causal reasoning, including experience from other prion diseases, shows that mechanisms exist for prenatal transmission and transmission by semen and embryos in both sheep and goats.