Lack of a cardiac bulge in human growth disorganized embryos: evidence for cardiac malformation leading to pregnancy failure

Abstract

Introduction: Cardiac malformations occur in some humans who have chromosome abnormalities or malformation syndromes. Genetic control of heart development has been investigated in animal models, and early pregnancy failure is observed in mice when certain genes are altered. We hypothesize that some Growth Disorganized (GD) human embryos have had a failure of cardiac development. We suggest that cardiovascular abnormalities contributed to the pregnancy failure and spontaneous abortion (SAB).

Methods: To test this, we reviewed the Embryo Collection of the Perinatal Pathology Service of Magee-Womens Hospital, comparing 35 externally normal embryos, Carnegie Stages 11-16, to 41 externally abnormal embryos, GD 2 and 3, for external evidence of normal heart formation: the presence of a heart bulge. We also evaluated the gross appearance of placenta] villi, if these were stored with the embryo. A difference in frequency of observations between the two groups was sought by χ2 analysis.

Results: Each 35 of the normal embryos had a heart bulge, and all 10 of the embryos with stored villi had grossly normal villi. The GD embryos were significantly different. Only 11 of 41 GD embryos (27%) had a heart bulge (X² =39.3, p<0.001). Of the 17 GD embryos stored with villous tissue, 8 had abnormal villi (47%, χ2 =4.55, p<0.05). The 8 GD embryos without a heart bulge were significantly more likely to have abnormal villi (7 of 8, 88%) when compared to the 9 GD embryos with a heart bulge (2 of 9, 22%, χ2 = 4.86 p<0.05).

Conclusions: GD embryos show evidence of failed cardiovascular development. Significantly fewer GD embryos have a heart bulge, and significantly more have abnormal placental villi compared to the normal embryos. Histologic studies of cardiovascular development in these embryos may be useful in understanding normal human heart formation and abnormal heart formation in some cases of pregnancy failure.