Low, Medium Levels of Mosaic Aneuploidy Among Embryos Don't Affect Birth Rates, Study Finds

NEW YORK — Low or medium levels of mosaic aneuploidy among embryos does not affect their developmental potential or pregnancy outcomes, a new study has found. This finding could increase the number of in vitro fertilization embryos available for implantation.

Currently, most embryos exhibiting aneuploidy are not selected for implantation during IVF, as aneuploidy is a common cause of pregnancy loss and congenital disorders. But some analyses have indicated that chromosomal mosaicism in embryos may sometimes be confined to a small number of cells that do not affect development.

Researchers from the reproductive genomics firm Igenomix and elsewhere examined the distribution of aneuploid chromosomes in pre-implantation embryos and trophectoderm biopsies, finding that when mosaicism levels were less than 50 percent, only a few aneuploidies affected other parts of the embryo. In a blinded clinical study, they further found no difference in live-birth or miscarriage rates between euploid and low- or medium-grade mosaic embryos, as they reported Thursday in the American Journal of Human Genetics.

"We believe the clinical data generated from this trial will resolve some of the major concerns that arise during pre-implantation genetic testing and will be of fundamental importance for helping many infertile patients make more informed reproductive decisions," first author Antonio Capalbo from Igenomix Italy said in a statement.

To examine the incidence of chromosomal mosaicism, the researchers first analyzed a historical dataset of 6,766 embryos. Biopsies of the samples' trophectoderms underwent next-generation sequencing-based analysis, which uncovered a diploid-aneuploid mosaicism incidence of 18.7 percent.

They additionally examined 91 unselected human blastocysts donated for research, collecting multiple trophectoderm samples and an inner cell mass sample for 75 of the embryos for sequencing. Through this, they found that chromosomal abnormalities in the inner cell mass were rare, even if the trophectoderm analysis suggested low- to medium-grade mosaicism. This suggests, the researchers said, that low- to medium-grade mosaicism in one trophectoderm biopsy could reflect aneuploidy that is limited in scope.

As the researchers suspected that these low- to medium-grade mosaic embryos may be just as likely to develop as euploid embryos, they conducted a multicenter double-blinded non-selection clinical trial that included 1,190 couples and 1,603 IVF cycles to examine the effect of mosaicism on birth and miscarriage rates.

In the study, blastocyst-stage embryos underwent pre-implantation genetic testing for aneuploidy. Embryos that were low-grade — or 20 percent to 30 percent — mosaic and embryos that were medium-grade — or 30 percent to 50 percent — mosaic were blindly reported as euploid, in addition to the embryos that were euploid. The embryos were then implanted based on standard morphological features. Embryos with more than 50 percent mosaicism were reported as aneuploid and excluded from the study.

In their analysis of 484 euploid, 282 low-grade, and 131 medium-grade mosaic embryos, there was no evidence that those levels of mosaicism affected live birth rates, the researchers found. For those embryos, the live birth rate was 42 percent, as compared to 43.4 percent for euploid embryos. Similarly, mosaicism did not appear to affect miscarriage rates. Additionally, obstetric and neonatal outcomes at birth were similar between the groups.

The results suggested to the researchers that embryos with low- or medium-grade mosaicism have similar reproductive potential as euploid embryos. They added that not having these embryos available for selection for implantation could have affected live birth rates following IVF treatment.

"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," Capalbo added. "Our findings suggest that reporting mosaicism as it is currently performed doesn't provide any element of clinical utility for IVF patients."