Chromosomal, Gestational, and Neonatal Outcomes of Embryos Classified as a Mosaic by Preimplantation Genetic Testing for Aneuploidy

Chromosomal segregation errors during mitosis can result in embryonic mosaicism, a phenomenon where different chromosomal copy numbers exist within a single embryo. Preimplantation genetic testing for aneuploidy (PGT-A) of multicellular biopsies can produce intermediate copy numbers in these cases, where some cells are disomic and some show monosomy or trisomy. When presented with mosaic results, some patients would take measures such as undergoing additional rounds of infertility treatment, procuring donor gametes or embryos, or giving up altogether on assisted reproductive technology. Although it has been shown that mosaic embryos have lower rates of implantation and higher rates of miscarriage, pregnancies that go to term result in seemingly healthy neonates, and further large analyses are needed analyzing chromosomal, obstetrical, and neonatal outcomes. This retrospective, multicenter, large-scale analysis aimed to compare pregnancies resulting from embryos classified as euploid or mosaic among patients seeking infertility treatment between 2017 and 2023. Data on prenatal chromosome testing, pregnancy information, obstetrical metrics, and neonate health were obtained from 9 infertility centers in 6 countries. Each mosaic embryo with a birth outcome was matched to a euploid embryo with a birth outcome considering the following: sex of embryo, maternal age, morphology grading, single or double transfer, and indication for PGT-A. Euploid versus mosaic embryos were compared with regard to spontaneous abortion rate, birth weight, length of gestation, incidence of birth defects, and chromosomal status during gestation. Mosaicism was defined using the 20% to 80% threshold, wherein the interval between chromosomal copy numbers 1.2 and 1.8 was considered mosaic loss, and 2.2 to 2.8 was considered mosaic gain. A total of 2031 mosaic embryos were included, of which 914 were successfully implanted. Of the 914, 203 pregnancies were spontaneous abortion (22.2%; 95% confidence interval [CI], 19.6%-25.0%). Among the euploid control group, an implantation rate of 59.1% and spontaneous abortion rate of 8.9% were observed. When chromosomal aberrations affecting only whole chromosomes (n = 1013) were analyzed, 39% (95% CI, 36%-42.1%) resulted in successful implantation, and 27.6% (95% CI, 23.2%-32.3%) of these experienced spontaneous abortion. Birth data were obtained on a total of 488 infants born through mosaic embryo transfer; however, no statistical difference was found between groups in regard to newborn weight, length of gestation, or birth defects. Most prenatal testing on pregnancies from mosaic ETs had normal results, and only 3 cases had mosaicism confirmed during gestation (1.2%; 95% CI, 0.25%-3.5%). The results of this study show that embryos designated as mosaics using PGT-A experience higher rates of early spontaneous abortions, and although mosaicism can persist through gestation in rare cases, it often resolves and leads to healthy infants.