title: DNA microarray reveals that high proportions of human blastocysts from women of advanced maternal age are aneuploid and mosaic.
abstract: Trophectoderm (TE) biopsy and DNA microarray have become the new technologies for preimplantation genetic diagnosis in humans. In this study, we comprehensively examined aneuploid formation in human blastocysts produced in vitro with microarray and investigated the clinical outcome after transfer of euploid embryos. Biopsied cells from either TE or inner cell mass (ICM) were processed for microarray to examine the errors in 23 pairs of chromosomes and the consistency between TE and ICM. It was found that 56.6% of blastocysts were aneuploid. Further analysis indicated that 62.3% of aneuploid blastocysts had single and 37.7% had multiple chromosomal abnormalities. Chromosome errors could occur in any chromosome, but errors in chromosome 21 accounted for the most (11.3%) among the 23 pairs of chromosomes. Transfer of array-screened blastocysts produced high pregnancy (70.2%) and implantation (63.5%) rates. Microarray of TE and ICM cells in the same blastocysts revealed that high proportions of aneuploid blastocysts (69.2%) were mosaic, including aneuploid TE and euploid ICM, inconsistent anomalies between ICM and TE, or euploid TE cells and aneuploid ICM in the same blastocyst. These results indicate that high proportions of human blastocysts produced in vitro from women of advanced maternal age are aneuploid and mosaic. Errors can occur in any of the 23 pairs of chromosomes in human blastocysts. Biopsy from TE in blastocysts does not exactly predict the chromosomal information in ICM if the embryos are aneuploid. Some mosaic blastocysts have euploid ICM, which may indicate important differentiate mechanism(s) of human preimplantation embryos.
authors.affiliation: Key Laboratory of Major Obstetrics Diseases of Guangdong Province, Guangzhou Medical College, Guangdong, China.
authors.forename: Jianqiao
authors.initials: J
authors.lastname: Liu
authors.forename: Weihua
authors.initials: W
authors.lastname: Wang
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Sun
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Jin
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Craig
authors.initials: C
authors.lastname: Witz
authors.forename: Dan
authors.initials: D
authors.lastname: Williams
authors.forename: Jason
authors.initials: J
authors.lastname: Griffith
authors.forename: Josh
authors.initials: J
authors.lastname: Skorupski
authors.forename: Gus
authors.initials: G
authors.lastname: Haddad
authors.forename: Jimmy
authors.initials: J
authors.lastname: Gill
mesh_terms: D000026:Abortion, Habitual / Q000503:physiopathology; D000328:Adult; D000375:Aging; D000782:Aneuploidy; D001755:Blastocyst / Q000378:metabolism* / Q000473:pathology; D053624:Blastocyst Inner Cell Mass / Q000378:metabolism / Q000473:pathology; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D015925:Cryopreservation; D004475:Ectoderm / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D010064:Embryo Implantation; D005260:Female; D005307:Fertilization in Vitro; D006801:Humans; D007247:Infertility, Female / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008423:Maternal Age; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D018873:Pregnancy Rate; D019836:Preimplantation Diagnosis; D012189:Retrospective Studies; D058989:Vitrification