The early days of IVF.

Fertilizing mammalian eggs in vitro has a history dating back to the early 20th century. Analyses on rodent embryos in short-term culture opened new prospects of research on human embryos in vitro. This phase of research really opened in the 1930s as Pincus and colleagues, Enzmann and Saunders, initially liberated immature rabbit oocytes from their follicles into culture media and discovered how 12 h was needed for their maturation. They also studied human oocytes and drew similar conclusion on timings. This misled later investigators who inseminated the eggs after 12 h in culture and failed to achieve fertilization. Another input into this investigation began in the 1950s, as Edwards completed his PhD on developmental genetics in mice. His studies on oocyte maturation and fertilization in vitro relied on identifying diakinesis and metaphase-2 as major markers of ongoing oocyte maturation. Mouse and other rodent eggs each required ca. 12 h, but primate and human eggs were found to need much longer. At this time, Edwards also worked with John Paul and Robin Cole in Glasgow and produced the world's first embryo stem cells, using rabbit embryos from the 2-cell stage to blastocysts. Disaggre-gated inner mass cells divided endlessly in vitro over 200 or more generations. When blastocysts were cultured intact, trophectoderm forms a thin pavement providing a surface for inner cell mass to differentiate into literally every tissue of the body. Fascinated by the therapeutic prospects of these stem cells, Edwards concentrated on maturing human oocytes in vitro to fertilize them in vitro and obtain human embryos for various purposes. An article on the problem of maturing human oocytes in vitro had already introduced the concept of PGD. Finally, human oocytes were found to require ca. 37 h for full maturation, which implied that insemination should be timed at 35–40 h to achieve fertilization (Edwards, 1965). Applying strict culture conditions based on earlier studies by Whitten, Biggers and Ham, and working largely with his PhD students in Cambridge, human eggs were fertilized in collaboration with Barry Bavister without any obvious need for sperm capacitation in 1969 (Edwards et al., 1969). PGD was finally introduced in rabbits in 1968, working with Richard Gardner who also revealed how single stem cells from mouse inner cell mass injected into recipient blastocysts could colonize all tissues in the resulting chimaeric embryos. Theories on the origin of chromosomal anomalies in mammalian embryos were also formulated at …