Abstract
Research question
What factors affect the proportion of chromosomally balanced embryos in structural
rearrangement carriers? Is there any evidence for an interchromosomal effect (ICE)?
Design
Preimplantation genetic testing outcomes of 300 couples (198 reciprocal, 60 Robertsonian,
31 inversion and 11 complex structural rearrangement carriers) were assessed retrospectively.
Blastocysts were analysed either by array-comparative genomic hybridization or next-generation
sequencing techniques. ICE was investigated using a matched control group and sophisticated
statistical measurement of effect size (φ).
Results
300 couples underwent 443 cycles; 1835 embryos were analysed and 23.8% were diagnosed
as both normal/balanced and euploid. The overall cumulative clinical pregnancy and
live birth rates were 69.5% and 55.8%, respectively. Complex translocations and female
age (≥35) were found to be risk factors associated with lower chance of having a transferable
embryo (P < 0.001). Based on analysis of 5237 embryos, the cumulative de-novo aneuploidy rate was lower in carriers compared to controls (45.6% versus 53.4%, P < 0.001) but this was a ‘negligible’ association (φ < 0.1). A further assessment
of 117,033 chromosomal pairs revealed a higher individual chromosome error rate in
embryos of carriers compared to controls (5.3% versus 4.9%), which was also a ‘negligible’
association (φ < 0.1), despite a P-value of 0.007.
Conclusions
These findings suggest that rearrangement type, female age and sex of the carrier
have significant impacts on the proportion of transferable embryos. Careful examination
of structural rearrangement carriers and controls indicated little or no evidence
for an ICE. This study helps to provide a statistical model for investigating ICE
and an improved personalized reproductive genetics assessment for structural rearrangement
carriers.
Keywords
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Biography
Çağrı Oğur is a senior clinical scientist working in the field of reproductive genetics since 2003. She has academic degrees in molecular biology, biomedical science and bioengineering. She has written more than 25 papers including articles, reviews and book chapters. Her research interests are the origin of chromosomal abnormalities in preimplantation embryos, non-invasive preimplantation genetic testing and the genetic basis of premature ovarian failure. She is currently working as a laboratory manager in Istanbul, Turkey.
Key message
Segregations were affected by rearrangement type and the carrier's sex, whereas female age was the dominant impact factor associated with de-novo aneuploidy. Carriers of balanced chromosome rearrangements did not exhibit higher aneuploidy rates for chromosomes not involved in the rearrangement, and the results revealed no evidence for an interchromosomal effect.
Article info
Publication history
Published online: July 30, 2022
Accepted:
July 25,
2022
Received in revised form:
July 17,
2022
Received:
March 22,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Declaration: The authors report no financial or commercial conflicts of interest.
Identification
Copyright
© 2022 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
