Prenatal gene therapy has the ability to target rapidly dividing cells, thus providing a large population of transduced cells that should provide a better therapeutic effect. The list of candidate diseases for prenatal gene therapy includes not only many single-gene disorders but also some pregnancy-specific conditions and structural abnormalities of the fetus. The ideal vector for fetal somatic gene therapy is the one that can produce long-term regulated and therapeutic expression of the transferred gene through the use of a single and efficient gene delivery method. Over the past few years, proof-of-principle studies in small-animal models have shown that prenatal gene therapy can result in permanent phenotypic correction of early single-gene disorders. Prenatal gene therapy in humans will depend critically on the ability to demonstrate its safety and efficiency in treating severe genetic disease. Improvements in vector design and safety and in delivery techniques to the fetus are the key.

This chapter discusses the consensus views obtained from the 57th Study Group on various aspects of reproductive genetics. It emphasizes that fetal karyotyping should remain the gold standard test following invasive prenatal diagnosis until appropriately tested and evaluated higher-resolution whole-genome analytical methods can be introduced. Preimplantation genetic diagnosis (PGD) for saviour siblings should be permitted or denied based on the permissibility or impermissibility of live-organ donation by children. Focused basic research is needed to understand the normal genetic and epigenetic events that occur during primordial germ cell specification from embryonic stem (ES) cells and in the differentiation of primordial germ cells. Improvements in vector design and safety will be needed before safe targeted delivery to the fetus can be achieved; studies into long-term safety in large animal models (non-human primates) should be supported. Research is needed into the long-term outcomes of novel therapeutic interventions.