All else being equal, are some mosaic embryos involving single chromosome more "preferred"?
Not all mosaic embryos involving single chromosome are created equal
Leila, one of our fellows, asked whether mosaic embryos involving single chromosome have different outcome among themselves.
Guidelines concerning the transfer of mosaic embryos
Not all mosaic embryos are created equal. American Society for Reproductive Medicine (ASRM) and Genetic Counseling Professional Group published a committee opinion regarding the transfer of mosaic embryos (Fertil Steril 2020;114:246–54). It can be summarized below:
Percentage of mosaicism: a lower percentage of mosaicism is associated with a higher implantation and ongoing pregnancy rate.
Specific chromosome(s) involved: There is no known correlation between specific mosaic chromosomes and the reproductive outcome.
Monosomy vs. trisomy: No differences in pregnancy or miscarriage rates between embryos mosaic for monosomies vs. trisomies.
Full chromosome vs. partial (segmental) chromosome: Embryos with segmental mosaic aneuploidy have higher ongoing pregnancy rates.
Number of chromosomes involved: the higher the number of chromosomes involved, the worse the outcome. Three is worse than two; two is worse than one.
Different chromosome may have different impact on fetal viability
The above committee opinion says no data to support differential impact of chromosomes on fetal viability. Nevertheless, it is biological plausible that each chromosome has its own influence on the development of an embryo (or a fetus). If the reverse were true, all 23 chromosomes should be equally represented in miscarriage samples.
A recent publication shows not all chromosomes are equally represented in tissue obtained from miscarriages which were conceived naturally (Cells 2025, 14(1), 8). For example, the percentage of trisomy 16 is disproportionately high.
What are mosaic embryos with “preferred” chromosomes?
If certain chromosomes are “not as bad as” others, mosaic embryos involving these chromosomes are the “preferred” embryos to transfer. Preimplantation Genetic Diagnosis International Society (PGDIS) published a position statement in 2019 regarding the transfer of mosaic embryos. It recommended prioritizing mosaic embryos with chromosomes 1, 3, 10, 12, 19, and avoiding chromosomes 13, 14, 16, 18, 21, and X.
The recommendation was based on a scoring system, considering the risks of miscarriage, fetal involvement, and uniparental disomy (UPD). The data was derived from chorionic villi sampling (Reprod Biomed Online. 2018 Apr;36(4):442-449).
“Preferred” mosaic embryo based on PGT-A
A systemic review (Archives of Gynecology and Obstetrics (2022) 306:1901–1911) sought to answer the question based on PGT-A data. The review includes all published data till May 2021; 6 studies with 1,106 cycles of single mosaic embryo transfer were analyzed.
The figure below sums up their findings. The X axis shows MR (miscarriage rate) scores, and the Y axis, OP/LBR (on-going pregnancy/Live birth rate) score. Higher score means better outcome, i.e., higher OP/LBR and lower MR.
It is concluded that in mosaic embryos involving single chromosome, the following chromosomes 7, 2, 1, 18, 11, X, 13, 14, 12, and 9 are preferred (color in red).
In conclusion
The conclusion is obviously based on limited data. Nevertheless, it is a good place to begin the discussion. More data will refine the conclusion.
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