Analysis Of Factors Related To Pregnancy Outcome After Mosaic Embryo Transfer

BackgroundMosaic embryo is the embryo containing two or more cell lines that carry different chromosomal compositions,which is common in preimplantation genetic testing(PGT).Mosaic embryos have significantly lower developmental potential and pregnancy outcomes(including clinical pregnancy rate,pregnancy continuation rate and live birth rate)compared to euploid embryos,but still have the potential to achieve live birth after transfer.Previous studies have suggested that the ratio of aneuploid cells in mosaic embryos(mosaic level),the type of aneuploid cells(mosaic type)and the age of egg retrieving may influence pregnancy outcomes of mosaic embryos,but there is no definitive conclusion made yet.ObjectiveTo investigate the pregnancy outcome of mosaic embryo transfer in nextgeneration sequencing(NGS)based-PGT,and the effect of different mosaic ratios and types on the pregnancy outcomes.MethodsRetrospectively analysed patients who underwent next-generation sequencing(NGS)-based PGT for assisted pregnancy in Center for Reproductive Medicine,Cheeloo College of Medicine,Shandong University from January 2018 to December 2020.308 cycles performing mosaic embryo transfer and 904 cycles of euploid embryo transfer at the same period were collected and defined as mosaic and euploid group,respectively.Pregnancy outcomes,including biochemical pregnancy rate,clinical pregnancy rate,ongoing pregnancy rate,early miscarriage rate,live birth rate and pregnancy complication rate,were compared between the mosaic and euploid groups.The mosaic groups were divided into two subgroups,low-and high-level mosaicism,according to mosaic ratio;and three subgroups,fragmental deletion/duplication,chromosomal monosomy/trisomy and complex mosaicism,according to the chimerism type;in order to analyse the effects of different mosaic ratios and types on the transfer outcome of mosaic embryos.ResultsThe mosaic group had significantly lower ongoing pregnancy rate(49.35%vs.58.19%,P=0.020,OR=0.924,95%CI=0.865-0.988)and live birth rate(48.38%vs.55.75%,P=0.031,OR=0.930,95%CI=0.870-0.994)compared to the euploidy group,while there was no difference in pregnancy complication rate between mosaic and euploid group.The high-level mosaic group had a significantly lower clinical pregnancy rate(47.50%vs.64.82%,P=0.043,OR=0.850,95%CI=0.727-0.995),ongoing pregnancy rate(37.50%vs.58.19%,P=0.009,OR=0.817,95%CI=0.703～0.950)and live birth rate(35.00%vs.55.75%,P=0.011,OR=0.820,95%CI=0.705～0.955)compared to euploidy embryos.The high-level mosaic group had a significantly lower live birth rate(35.00%vs.50.37%,P=0.028,OR=0.840,95%CI=0.719～0.981)compared to low-level mosaic group.The biochemical pregnancy rate(58.49%vs.70.91%,P=0.020,OR=0.889,95%CI-0.809～0.982),clinical pregnancy rate(49.06%vs.64.82%,P=0.003,OR=0.864,95%CI=0.783～0.953),ongoing pregnancy rate(43.40%vs.58.19%,P=0.003,OR=0.864,95%CI=0.784～0.952)and live birth rate(43.30%vs.55.75%,P=0.003,OR=0.877,95%CI=0.795～0.966)of chromosomal monosomy/trisomy mosaic group were significantly lower than euploid group,while there was no significant difference in pregnancy outcomes between fragmental deletion/duplication mosaic group and euploid group.The biochemical pregnancy rate(64.47%vs.84.13%,P=0.002,OR=0.793,95%CI=0.683～0.920),clinical pregnancy rate(57.89%vs.77.78%,P=0.006,OR=0.814,95%CI=0.702～0.943),ongoing pregnancy rate(47.37%vs.68.25%,P=0.017,OR=0.829,95%CI=0.711～0.967)and live birth rate(46.05%vs.65.08%,P=0.042,OR=0.850,95%CI=0.726～0.994)of fragmental deletion mosaic group were significantly lower than fragmental duplication mosaic group.ConclusionSome mosaic embryos can still result in healthy live births after transfer.Different mosaic ratios or types affect the pregnancy outcome of mosaic embryos.Therefore,in clinical genetic counselling,the order of mosaic embryos for transfer should be considered to obtain the best pregnancy outcome for patients who have no euploid embryos available.