The extent of chromosomal mosaicism influences the clinical outcome of in vitro fertilization treatments

Abstract

Recently, we have demonstrated that mosaic embryos hold the potential to implant and result in the birth of healthy babies1. The aim of this study was to determine whether the extent of chromosomal mosaicism can influence the development potential of mosaic embryos. The transfer of mosaic embryos at different aneuploidy percentage was offered to 77 women for whom IVF had resulted in no euploid embryos between May 2013-March 2016. The clinical outcome obtained after transfer of mosaic embryos with low (<50%) and high (≥50%) aneuploidy percentage, was compared with those resulting from a control group of 251 euploid blastocysts. We aimed to assess if there was any statistically significant difference in the development potential between these groups. All embryos were cultured to blastocyst stage; trophectoderm biopsy was performed on Day-5 of development or Day6/7 for slow growing embryos. Comprehensive chromosome screening PGS was performed using either NGS or array-CGH methodologies. Transfers of mosaic embryos with a high percentage of chromosomally abnormal cells (≥50%) resulted in a live birth rate of 15.1% and involved a miscarriage rate of 9%. In contrast, mosaic embryos with a lower aneuploidy percentage (<50%) resulted in a live birth rate of 42.2%, with a miscarriage occurring in 7.0% of the transfers. All pregnancies that went to term were confirmed, through sampling of the chorionic villi and/or amniotic liquid, to have a normal karyotype. Mosaic embryos with high aneuploidy percentage (≥50%) showed significantly lower implantation rate (24.4% vs 54.6%; P=0.001) and live birth rate (15.1% vs 46.6%; P=0.001) than euploid blastocysts. In contrast, embryos with lower aneuploidy percentage (<50%) have similar clinical outcomes of those euploid. The biochemical pregnancy rate and miscarriage rate were not significantly different between the two groups (Table 1). The results of this study further confirm that mosaic embryos can develop into healthy euploid newborns. We demonstrated that the extent of mosaicism affects the IVF success rate. Priority for transfer should be given to mosaic embryos with low mosaicism levels.Table 1Comparison of clinical outcomes in euploid embryos vs mosaic embryo different mosaicism levelEuploidMosaic with <50%pMosaic with >50%pNo. of embryos transferred2514533No. of transfer2504433No. of positive beta hCG160 (64%)26 (59%)0.411 (33.3%)0.001No. of Biochemical pregnancies24 (9.6%)5 (11.36%)0.83 (9.1%)0.8No. of embryos implanted137 (54.6%)22 (48.9%)0.58 (24.4%)0.01No. of Early abortion20 (8.0%)3 (6.8%)0.83 (9.1%)0.9No. of Ongoing clinical pregnancies per ET117 (46.6%)19 (42.2 %)0.75 (15.1%)0.001No. of Pregnancies went to term116 (46.4%)18 (41%)0.45 (15.1%)0.001No. of Babies Born117 (46.6%)19 (42.2 %)0.75 (15.1%)0.001 Open table in a new tab