The search for the perfect human embryo is over

Back on May 13th I wrote a post entitled “Evolutionary biology takes a hard look at IVF and human conception”. In it I suggested that aneuploidy – chromosomal abnormality – was in fact normal for human embryos and had evolved as a male strategy for invasiveness in the face of female counter-measures that encapsulated implanting embryos and inspected them for quality and/or compatibility before either accepting or rejecting them. I observed that although fertility failure in human reproduction is very high at about 70%, it is much lower than the amount of chromosomally-abnormal embryos which is in excess of 90%. The obvious conclusion is that some genetically abnormal embryos can go on to make perfectly normal babies.

This sets up the obvious question. How do abnormal embryos “right themselves”? How do they correct these genetic mistakes, or purge them from the developing embryo, once they have neatly side-stepped a mother’s defenses? I suggested that the answer might lie in recent research by Magdalena Zernicka-Goetz of the Gordon Institute in Cambridge, UK, who discovered, thanks to chorionic villus sampling, that 25% of the cells in the placenta of a baby she was incubating at the age of 44 contained aneuploidies. Thankfully her baby was born completely normal. But this motivated Zernicka-Goetz to research the question of why the placenta could be riddled with genetic abnormality but the baby preserved from it. Research with mice embryos made mosaic for aneuploid and normal cells suggested that intense clonal competition among the blastocyst cells that went on to make the baby eradicated all cells that were genetically abnormal, whereas that clonal competition in the fraction of cells that went on to form the placenta was relaxed – allowing clones of aneuploid cells to survive. I suggested to Zernicka-Goetz that this could be an evolved mechanism to retain aneuploidy in the placenta in order to imbue it with the same degree of invasiveness that aneuploidy had already bestowed on the early embryo.

A paper in the journal Reproductive Biology and Endocrinology last week documents five cases of healthy live births of babies formed from aneuploid embryos and questions the necessity for, and effectiveness of, pre-implantation genetic screening, which has been widely adopted by IVF clinics in an attempt to identify aneuploidy in embryos and thus weed out “unviable” embryos. The paper argues that PGS should be abandoned because it may do more harm than good because it produces too many false positives which leads to over-rejection of embryos that could have gone on to make perfectly fine babies. A classic case of iatrogenic medicine that might be adding to the patients’ infertility, not curing it. If so, although these authors do not invoke evolutionary mechanisms explicitly, this story might endure as a prime example of where evolutionary medicine can make a real contribution to medical practice by fundamentally questioning assumptions. The search for the perfect embryo may very well be over.