@article{6ca32030339c46fe958d91ed61b9e8c6,
title = "In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages",
abstract = "Although chromosomal instability (CIN) is a common phenomenon in cleavage-stage embryogenesis following in vitro fertilization (IVF)(1-3), its rate in naturally conceived human embryos is unknown. CIN leads to mosaic embryos that contain a combination of genetically normal and abnormal cells, and is significantly higher in in vitro-produced preimplantation embryos as compared to in vivo-conceived preimplantation embryos(4). Even though embryos with CIN-derived complex aneuploidies may arrest between the cleavage and blastocyst stages of embryogenesis(5,6), a high number of embryos containing abnormal cells can pass this strong selection barrier(7,8). However, neither the prevalence nor extent of CIN during prenatal development and at birth, following IVF treatment, is well understood. Here we profiled the genomic landscape of fetal and placental tissues postpartum from both IVF and naturally conceived children, to investigate the prevalence and persistence of large genetic aberrations that probably arose from IVF-related CIN. We demonstrate that CIN is not preserved at later stages of prenatal development, and that de novo numerical aberrations or large structural DNA imbalances occur at similar rates in IVF and naturally conceived live-born neonates. Our findings affirm that human IVF treatment has no detrimental effect on the chromosomal constitution of fetal and placental lineages.",
keywords = "HIDDEN-MARKOV MODEL, HUMAN-EMBRYOS, CHROMOSOME INSTABILITY, MOSAICISM, GENOME, ANEUPLOIDY, COMMON, ABNORMALITIES, CONSTITUTION, BLASTOCYSTS",
author = "Esteki, {Masoud Zamani} and Triin Viltrop and Olga Tsuiko and Airi Tiirats and Mariann Koel and Margit Noukas and Olga Zilina and Katre Teearu and Heidi Marjonen and Hanna Kahila and Jeroen Meekels and Viveca Soderstrom-Anttila and Anne-Maria Suikkari and Aila Tiitinen and Reedik Magi and Sulev Koks and Nina Kaminen-Ahola and Ants Kurg and Thierry Voet and Vermeesch, {Joris Robert} and Andres Salumets",
note = "Funding Information: We gratefully thank all families that participated in this study in Estonia and Finland. This research was funded by an institutional research grant from the Estonian Ministry of Education and Research (no. IUT34-16 to A.S.); Enterprise Estonia (grant no. EU48695 to A.S.); the Horizon 2020 innovation (WIDENLIFE) (grant no. EU692065 to A.K.); the European Union{\textquoteright}s FP7 Marie Curie Industry-Academia Partnerships and Pathways (grant no. EU324509 to A.S.); the Helsinki University Hospital fund (to A.Tiitinen); the Faculty of Medicine, University of Helsinki fund (to N.K.-A.); the EVA (Erfelijkheid Voortplanting & Aanleg) specialty program fund of Maastricht University Medical Centre (MUMC+) (to M.Z.E.); the Estonian Research Council (grant nos. IUT20-60 and IUT24-6); the European Union through the European Regional Development Fund Project (nos. 2014-2020.4.01.15-0012 GENTRANSMED and 2014-2020.4.01.16-0125 to R.M.); and KU Leuven funding (no. C1/018) and FWO grant (no. G.0392.14N to J.R.V. and T.Voet). We thank B. de Greef, A. van Montfoort and N. Davarzani for statistical consultations. Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2019",
month = nov,
day = "4",
doi = "10.1038/s41591-019-0620-2",
language = "English",
volume = "25",
pages = "1699--1705",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "11",
}