Abstract
Research question
To analyse why unbalanced viable offspring are derived mainly from the 3:1 segregation
mode in t(11;22)(q23;q11.2) reciprocal translocation.
Design
Retrospective analysis of 24 pre-implantation genetic testing for chromosomal structural
re-arrangements (PGT-SR) cycles was performed on seven male and five female carriers
of t(11;22) translocation. Sperm analysis was performed on each male carrier. These
patients were directed to the study centre after several years of miscarriages and/or
abortions, primary infertility for male carriers or birth of an affected child.
Results
Twenty-four PGT-SR cycles were performed to exclude imbalances in both male and female
carriers. The unbalanced embryos derived from the adjacent-1 segregation mode were
the most represented in both male and female carriers (68.4% and 50%, respectively).
These results were positively related with meiotic segregation analysis of reciprocal
translocation in spermatozoa. A thorough analysis of the unbalanced embryo karyotypes
determined that the expected viable +der22 karyotype resulting from 3:1 malsegregation
was less represented at 5.3%.
Conclusions
These findings highlight the divergence that may exist between meiotic segregation
and post-zygotic selection. Post-zygotic selection would be responsible for the elimination
of unbalanced embryos derived from the adjacent-1 segregation mode. The combined action
of several factors occurs at the beginning of post-zygotic selection. Genetic counselling
must consider the risk of a birth related to the adjacent-1 segregation mode, irrespective
of the sex of the translocation carrier. These results will allow deeper understanding
of the PGT results of t(11;22) carriers, which often include a high number of aneuploid
embryos.
KEYWORDS
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Biography
Reda Zenagui received his PhD in Molecular Biology from the University of Montpellier, France in 2011. He specializes in monogenic disorders. He is now part of the Pre-implantation Genetic Diagnostic Unit at Montpellier Hospital, focusing on improving reproductive care in patients with chromosomal abnormalities.Key message
This study ascertained that the adjacent-1 segregation mode was the predominant imbalance in spermatozoa and embryos. However, the adjacent-1 products undergo post-zygotic selection responsible for their elimination. Therefore, post-zygotic selection would favour a viable offspring derived from the 3:1 segregation mode.
Article info
Publication history
Published online: March 11, 2019
Accepted:
February 28,
2019
Received in revised form:
February 19,
2019
Received:
November 30,
2018
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
