Assessing the Viability of Segmental Aneuploid Embryos: A Chromosomal Concordance Study of 175 Human Blastocysts

Abstract

Preimplantation genetic testing for aneuploidy (PGT-A) is widely used to select euploid embryos for in vitro fertilization (IVF), but its accuracy in predicting the implantation potential for full segmental aneuploid (Seg-A) embryos remains unclear. In this study, we investigated chromosomal concordance between clinically biopsied trophectoderm (TE) and inner cell mass (ICM) in 175 donated blastocysts, which comprised those clinically diagnosed as euploid (13), Seg-A (36), segmental mosaicism (Seg-M) (60), whole-chromosome aneuploid (Who-A) (52), and whole-chromosome mosaicism (14). Using next-generation sequencing (NGS), we found that TE-ICM concordance rates were higher for euploid (85%) and Who-A (94%) embryos but significantly lower for Seg-A (25%) and Seg-M embryos (33%). For Seg-A, the euploidy rate in the ICM was 19% and the euploidy rate in the ICM was 63% for Seg-M. These low concordance rates may be due to technical and biological artifacts of PGT-A for Seg-A. Despite the significant discordance between TE and ICM, a subset of Seg-A embryos demonstrated euploidy. While clinically diagnosed euploid embryos remain the preferred choice, Seg-A embryos should be considered as having implantation potential. In particular, Seg-A results should be clearly distinguished from Who-A results and not routinely categorically discarded. Further research is required to refine the selection criteria, aided by parental karyotyping or re-biopsy, and to develop more reliable embryo assessment methods to ensure the accurate evaluation of reproductive potential and support shared decision making between doctors and patients.

Keywords: preimplantation genetic testing for aneuploidy (PGT-A); segmental aneuploidy (Seg-A); segmental mosaicism (Seg-M); trophectoderm (TE) biopsy.

Figure 1

Study flowchart. (A) A total of 175 blastocysts were donated by 89 couples. The original PGT-A results of the donated blastocysts are displayed in the second row. PGT-A results from the original trophectoderm (TE) biopsy indicated 13 euploid, 74 mosaic, and 88 aneuploid blastocysts. Of the 74 mosaic blastocysts, 14 exhibited whole-chromosome mosaicism, while 60 displayed segmental mosaicism; of the 88 aneuploid blastocysts, 52 showed whole-chromosome aneuploidy, and 36 exhibited Seg-A. Chromosome status of mosaic and aneuploidy blastocysts is displayed in the third row. (B) The location of the ICM re-biopsy and initial clinical TE biopsy sites (ICM: inner cell mass; TE: trophectoderm). (C) Isolation of the ICM from a blastocyst. The blastocyst is positioned for micromanipulation. The ICM, marked by the arrow, is targeted for isolation and then aspirated into the micropipette, demonstrating the successful extraction process. (scale bar = 50 μm)

Figure 2

Concordance between original TE biopsy and ICM chromosome status. Bar plots show the distribution of ICM chromosome status among embryos grouped by original TE biopsy results. Superscript letters (a–k) indicate statistically significant pairwise differences between groups, based on the chi-square test. Each letter represents a specific comparison; identical letters denote two values that are significantly different from each other (p < 0.05).

Figure 3

Concordance and discordance of PGT-A results between original TE biopsy and ICM. This figure presents the concordance and discordance of segmental aneuploidy (Seg-A) and segmental mosaicism (Seg-M) between the original trophectoderm (TE) biopsy and the inner cell mass (ICM). (A,B) Concordance of Seg-A: both the original TE biopsy (A) and ICM (B) exhibit the same segmental aneuploidy (loss of 12p13.33p11.21), as indicated by the red arrows. (C,D) Discordance of Seg-A: the original TE biopsy (C) shows segmental aneuploidy (gain of 6q13–27 and 30% mosaic loss of 6p25.3–q13, marked by red and blue arrows), while the ICM (D) is euploid. (E,F) Concordance of Seg-M: the original TE biopsy (E) and ICM (F) both show mosaicism, with consistent segmental mosaic loss (6q12–27) and additional mosaic loss regions in (E), indicated by blue arrows. (G,H) Discordance of Seg-M: the original TE biopsy (G) shows 60% mosaic loss of 2p25.3–13.2 and 40% mosaic loss of 6q12–14.3, while the ICM (H) is euploid.