The nature of aneuploidy with increasing age of the female partner: a review of 15,169 consecutive trophectoderm biopsies evaluated with comprehensive chromosomal screening

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Abstract

To determine the relationship between the age of the female partner and the prevalence and nature of human embryonic aneuploidy. Retrospective. Academic. Trophectoderm biopsies. Comprehensive chromosomal screening performed on patients with blastocysts available for biopsy. Evaluation of the impact of maternal age on the prevalence of aneuploidy, the probability of having no euploid embryos within a cohort, the complexity of aneuploidy as gauged by the number of aneuploid chromosomes, and the trisomy/monosomy ratio. Aneuploidy increased predictably after 26 years of age. A slightly increased prevalence was noted at younger ages, with >40% aneuploidy in women 23 years and under. The no euploid embryo rate was lowest (2% to 6%) in women aged 26 to 37, was 33% at age 42, and was 53% at age 44. Among the biopsies with aneuploidy, 64% involved a single chromosome, 20% two chromosomes, and 16% three chromosomes, with the proportion of more complex aneuploidy increasing with age. Finally, the trisomy/monosomy ratio approximated 1 and increased minimally with age. The lowest risk for embryonic aneuploidy was between ages 26 and 30. Both younger and older age groups had higher rates of aneuploidy and an increased risk for more complex aneuploidies. The overall risk did not measurably change after age 43. Trisomies and monosomies are equally prevalent. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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To err (meiotically) is human: the genesis of human aneuploidy.

Terry Hassold, Patricia Hunt (2001)

Aneuploidy (trisomy or monosomy) is the most commonly identified chromosome abnormality in humans, occurring in at least 5% of all clinically recognized pregnancies. Most aneuploid conceptuses perish in utero, which makes this the leading genetic cause of pregnancy loss. However, some aneuploid fetuses survive to term and, as a class, aneuploidy is the most common known cause of mental retardation. Despite the devastating clinical consequences of aneuploidy, relatively little is known of how trisomy and monosomy originate in humans. However, recent molecular and cytogenetic approaches are now beginning to shed light on the non-disjunctional processes that lead to aneuploidy.

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Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial.

Kathleen M. Upham, Nathan R Treff, Deanne Taylor … (2013)

To determine whether blastocyst biopsy and rapid quantitative real-time polymerase chain reaction (qPCR)-based comprehensive chromosome screening (CCS) improves in vitro fertilization (IVF) implantation and delivery rates. Randomized controlled trial. Academic reproductive medicine center. Infertile couples in whom the female partner (or oocyte donor) is between the ages of 21 and 42 years who are attempting conception through IVF. Embryonic aneuploidy screening. Sustained implantation and delivery rates. We transferred 134 blastocysts to 72 patients in the study (CCS) group and 163 blastocysts to 83 patients in the routine care (control) group. Sustained implantation rates (probability that an embryo will implant and progress to delivery) were statistically significantly higher in the CCS group (89 of 134; 66.4%) compared with those from the control group (78 of 163; 47.9%). Delivery rates per cycle were also statistically significantly higher in the CCS group. Sixty one of 72 treatment cycles using CCS led to delivery (84.7%), and 56 of 83 (67.5%) control cycles ultimately delivered. Outcomes were excellent in both groups, but use of CCS clearly improved patient outcomes. Blastocyst biopsy with rapid qPCR-based comprehensive chromosomal screening results in statistically significantly improved IVF outcomes, as evidenced by meaningful increases in sustained implantation and delivery rates. NCT01219283. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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Cleavage-stage biopsy significantly impairs human embryonic implantation potential while blastocyst biopsy does not: a randomized and paired clinical trial.

R. Scott, E N Forman, Nathan R Treff … (2013)

To determine if cleavage- or blastocyst-stage embryo biopsy affects reproductive competence. Paired randomized clinical trial. Academic-assisted reproduction program. Attempting conception through IVF. After selecting two embryos for transfer, one was randomized to biopsy and the other to control. Both were transferred within shortly thereafter. The biopsy was submitted for microarray analysis and single-nucleotide polymorphism (SNP) profiling. Buccal DNA obtained from the neonate after delivery had microarray analysis and SNP profile compared with that of the embryonic DNA. A match confirmed that the biopsied embryo implanted and developed to term, whereas a nonmatch indicated that the control embryo had led to the delivery. Paired analysis of the delivery rates of the transferred embryos. Either twin delivery or failure to deliver represents equivalent outcomes for the biopsied and control embryos. In contrast, singletons were determined to be from the biopsied or the control embryo. Blastomere biopsy on day 3 of development resulted in a significant reduction in sustained implantation. Only 30% of biopsied embryos had sustained implantation and ultimately developed into live-born infants versus 50% of unbiopsied controls, a relative reduction of 39%. In contrast, sustained implantation rates were equivalent (51% vs. 54%) for biopsied and control blastocysts. Cleavage-stage biopsy markedly reduced embryonic reproductive potential. In contrast, trophectoderm biopsy had no measurable impact and may be used safely when embryo biopsy is indicated. NCT01219504. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.