Abstract
Study question
Which ethical and clinical aspects should be considered for preimplantation genetic testing PGT-SR strategy management for a consanguineous couple carrying the same reciprocal translocation?
Summary answer
PGT-SR management required specific probe designs to distinguish chromosomal patterns of balanced embryos, leading to complex transfer choices that required an adapted genetic counseling.
What is known already
Reciprocal translocation is a classic case in PGT-SR management, since all balanced embryos are transferable without distinguish between normal and balanced embryos. In accordance with the several recommendations, professionals calculated the reproductive risk related to the abnormalities and established an appropriate genetic counseling. However, an extreme case, such as the same reciprocal translocation carried by both members of a couple complicates PGT-SR management at all levels. Mainly, the genetics counseling around balanced embryo transfers. To date, only one study has reported a similar case, however, genetic counseling and the choice of embryos to be transferred have been poorly documented
Study design, size, duration
This study reports an extremely rare case of a couple (26-year-old woman and 29-year-old man) who was referred to our PGT center of the Montpellier University Hospital after 4 spontaneous miscarriages. The couple, first degree cousins in whom both partners are carrying the same reciprocal translocation 46,XX/XY,t(3;18) t(q26.1;q12.1). The patients were informed of the investigations and gave their consent before participation in the study.
Participants/materials, setting, methods
Peripheral blood of each member was investigated by FISH to caracterize chromosomal breakpoints. Secondly, a theoretical estimation of different segregation products to find a normal or balanced embryos were performed considering the extreme complexity of the case. Finally, an adapted PGT-SR probe strategy was conceived and proposed to a couple. Choices of balanced embryos to transfer were detailed to ensure that the patient is aware of risks and potential benefits.
Main results and the role of chance
In this particular case where both members of the couple are carrying the same reciprocal translocation, the chance of finding a normal or balanced embryo was further lowered 2% (4/196). It is estimated that the couple would produce 1 normal embryo and 15 balanced embryos. Diagnostic was possible on 16 biopsied embryos on day 3. Probe signal interpretations revealed four balanced embryos. Two embryos were proposed for a transferred on day 4. These balanced embryos had a different probe patterns, the first balanced embryo was normal and the second balanced embryo resulting from an adjacent–1 segregation mode presented an uniparental disomy (UPD).
Limitations, reasons for caution
ESHRE recommendations were established for common chromosomal rearrangements. In specific cases, limitations are strongly related to the complexity of the human genome. In this study, the choice of the embryos to be transferred depended entirely to our knowledge of phenotypic consequences of a homozygous gene alterations involved in chromosomal breakpoints.
Wider implications of the findings: Professionals were confronted with requests to transfer balanced embryos with a partial/complete UPD or a balanced double translocation homozygote to improve the transfer rate from 3/196 of balanced combinations to 16/196. Dilemma between risks and benefits were considered for counseling to ensure an informed decision-making by patients.
Trial registration number
NA
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