A recent study has suggested that many embryos from IVF that are discarded due to chromosomal abnormalities have the potential to lead to successful pregnancies.
Aneuploidy is the leading cause of embryo implantation failure, pregnancy loss and congenital disorders. One of the major causes of this is chromosome segregation errors in oocytes. However, recent observations have suggested that aneuploidy can also arise during preimplantation embryonic divisions. Aneuploidies with meiotic errors are present uniformly throughout the embryo. Whereas those with mitotic origins give rise to cell lineages with different chromosomal content. This is known as embryonic mosaicism.
Understanding how often mosaicism occurs and the distribution of these aneuploid cells is critical as genetic testing of preimplantation embryos and prenatal foetuses is routine practice. Mosaicism has a major clinical impact as fewer than 3% of mosaic embryos are used in babies born after in vitro fertilisation (IVF) treatment. Our understanding of the developmental potential of these mosaic embryos remains unclear.
The prevalence of aneuploid cells in IVF embryos
In a recent study, published in AJHG, researchers investigated the prevalence and distribution of aneuploid cells in the largest dataset of disaggregated human blastocysts. More specifically, they followed 73 unselected preimplantation embryos and 365 biopsies, sampled from four multifocal trophectoderm (TE) samples and the inner cell mass (ICM). They found that when mosaicism impacted less than 50% of cells in the TE biopsy, only 1% of aneuploidies affected other portions of the embryo.
The team also conducted a double-blind trial in which patients undergoing IVF at five hospitals had their embryos tested with pre-implantation genetic testing that specifically looked for mosaic aneuploidy. They found that embryos with low-grade mosaicism (20%–30% aneuploid cells) and medium-grade mosaicism (30%–50% aneuploid cells) were blindly reported as euploid and implanted. The trial showed equivalent live-birth rates and miscarriage rates across 484 euploid, 282 low-grade mosaic, and 131 medium-grade mosaic embryos.
First author, Antonio Capalbo, expressed:
“We did this study because we were concerned about the unmotivated dismissal of putative mosaic embryos from clinical use without robust data to support this practice.
Our findings suggest that reporting mosaicism as it is currently performed doesn’t provide any element of clinical utility for IVF patients. Accordingly, it seems reasonable these genetic findings not be reported after pre-implantation genetic testing, similar to what is done for variants of unknown significance in clinical genetic testing. If these findings are reported, patients should be aware that the embryos are otherwise healthy and normal.”
The team hope this study will directly impact clinical practice, pushing for an update of guidelines and recommendations that will allow IVF patients to improve their decision-making process when evaluating the transfer of mosaic embryos.
Image credit: canva