Hypothesis: human trophectoderm biopsy downregulates the expression of the placental growth factor gene.

Preeclampsia (PE) and intrauterine growth retardation (IUGR) are the results of defective placentation associated with the downregulation of different genes in the human trophoblast including the Placental Growth Factor (PGF). TrophEctoderm (TE) biopsy is increasingly performed for Pre-implantation Genetic Testing of Aneuploidies and it involves the traumatical removal of an unpredictable number of mural TE cells from the human blastocyst. We observed strikingly similar obstetrical and neonatal complications in pregnancies where the placenta bears PGF downmodulation or a TE biopsy has been done. In both groups, the risk of PE, IUGR, congenital cardiac ventricular septal defects, caesarean section, sex ratio in favour of males and preterm birth is significantly increased compared to controls. Given the high degree of correlation, the observation may not be a casual one. We postulate herein that the TE biopsy may induce persistent dysregulation of different genes in the placenta including PGF. The mechanism proposed is the disruption of tight junctions caused by the TE biopsy.