title: Analysis of implantation and ongoing pregnancy rates following the transfer of mosaic diploid-aneuploid blastocysts.
abstract: Preimplantation genetic testing for aneuploidy (PGT-A) is widely used in IVF and aims to improve outcomes by avoiding aneuploid embryo transfers. Chromosomal mosaicism is extremely common in early development and could affect the efficacy of PGT-A by causing incorrect embryo classification. Recent innovations have allowed accurate mosaicism detection in trophectoderm samples taken from blastocysts. However, there is little data concerning the impact of mosaicism on viability, and the optimal clinical pathway for such embryos is unclear. This study provides new information concerning the extent to which mosaic preimplantation embryos are capable of producing pregnancies and births. Archived trophectoderm biopsy specimens from transferred blastocysts were analyzed using next generation sequencing (NGS). Unlike other PGT-A methods, NGS accurately detects mosaicism in embryo biopsies. 44 mosaic blastocysts were identified. Their clinical outcomes were compared to 51 euploid blastocysts, derived from a well-matched, contemporary control group. Mosaic embryos were associated with outcomes that were significantly poorer than those of the control group: implantation 30.1 versus 55.8% (P = 0.038); miscarriage rate 55.6 versus 17.2% (P = 0.036); and ongoing pregnancy 15.4 versus 46.2% (P = 0.003). 61% of the mosaic errors affected whole chromosomes and 39% were segmental aneuploidies. Embryo viability is compromised by the presence of aneuploid cells. However, a minority of affected embryos can produce successful pregnancies. Hence, such embryos should not necessarily be excluded, but given a lower priority for transfer than those that are fully euploid. It is recommended that pregnancies established after mosaic embryo transfers be subjected to prenatal testing, with appropriate patient counselling.
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, UK. elpida@reprogenetics.co.uk.|Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK. elpida@reprogenetics.co.uk.
authors.forename: Elpida
authors.initials: E
authors.lastname: Fragouli
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, UK.
authors.forename: Samer
authors.initials: S
authors.lastname: Alfarawati
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, UK.|Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
authors.forename: Katharina
authors.initials: K
authors.lastname: Spath
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, UK.|Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
authors.forename: Dhruti
authors.initials: D
authors.lastname: Babariya
authors.affiliation: 9.Baby, Family and Fertility Center Bologna, Bologna, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Tarozzi
authors.affiliation: 9.Baby, Family and Fertility Center Bologna, Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Borini
authors.affiliation: Reprogenetics UK, Institute of Reproductive Sciences, Oxford Business Park North, Oxford, OX4 2HW, UK.|Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford, UK.
authors.forename: Dagan
authors.initials: D
authors.lastname: Wells
mesh_terms: D000328:Adult; D000782:Aneuploidy; D001755:Blastocyst / Q000166:cytology / Q000378:metabolism; D016022:Case-Control Studies; D004171:Diploidy; D010064:Embryo Implantation; D004624:Embryo Transfer / Q000379:methods*; D005260:Female; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007621:Karyotyping; D009030:Mosaicism / Q000196:embryology*; D011247:Pregnancy; D018873:Pregnancy Rate; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA