Why Euploid Blastocysts Fail

Abstract

Preimplantation genetic testing for aneuploidy improves implantation and reduces miscarriage rates, but still about 30 to 35% of euploid blastocysts fail to implant and 10 to 13% of pregnancies following euploid blastocyst transfer miscarry. Both endometrial and embryo factors may contribute to failed euploid embryo transfers. Endometrial factors include uterine structural abnormalities, altered timing of endometrial receptivity, glandular-stromal disynchrony, and inflammatory states. Recent studies question the clinical benefit of some recent assays for endometrial receptivity. Other recent studies question the value of surgical correction of uterine septae and fibroids to prevent further pregnancy loss. Embryo factors include aneuploidy, either undetected by PGT-A performed on the blastocyst trophectoderm (i.e. false negative test) or de novo non-disjunction. Sub chromosomal genetic variation, e.g. copy number variants and de novo retrotransposon insertions, may impair embryo viability. We employ a “genetics first” approach, which relies on genetic analysis of products of conception, obtained by uterine evacuation, to evaluate miscarriage after euploid blastocyst transfer. Non-invasive genetic analysis of first trimester pregnancies also may help characterize the cause of embryo loss after euploid embryo transfer. Early results suggest that analysis of cfDNA and trophoblast retrieval and isolation from the cervix (TRIC) may allow women experiencing early pregnancy loss to learn about the genetic state of their miscarriage, without an invasive surgical procedure to obtain products of conception.