What is the difference between euploid, aneuploid, and mosaic (having a mixture of normal and abnormal cells) embryos in terms of genetic composition?

From the Guidelines

Euploid embryos are the most desirable for pregnancy success, containing the correct number of chromosomes (46 in humans). Aneuploid embryos have an abnormal chromosome count, either too many or too few, which typically leads to implantation failure, miscarriage, or genetic disorders if pregnancy proceeds. Mosaic embryos represent a middle ground, containing a mixture of both normal and abnormal cells, with varying pregnancy potential depending on the percentage and type of abnormal cells present. During IVF procedures, preimplantation genetic testing (PGT) can identify these embryo types, with doctors typically prioritizing euploid embryos for transfer. If only mosaic embryos are available, those with lower percentages of abnormal cells or abnormalities in less critical chromosomes may be considered for transfer after thorough genetic counseling. The concept of mosaicism, as described in a study published in Nature Reviews Drug Discovery 1, is crucial in understanding the complexity of embryo chromosomal status, where mosaicism is defined as the presence of cells of multiple different genotypes within a single animal or cell population. Key points to consider when evaluating embryo types include:

• Euploid embryos: optimal choice for transfer due to their normal chromosomal count
• Aneuploid embryos: generally not recommended for transfer due to high risk of implantation failure or genetic disorders
• Mosaic embryos: may be considered for transfer if the percentage of abnormal cells is low and after thorough genetic counseling
• Maternal age: a significant factor in determining embryo chromosomal status, with older women producing higher rates of aneuploid embryos.

From the Research

Euploid, Aneuploid, and Mosaic Embryos

• Euploid embryos have a normal chromosome complement, while aneuploid embryos have an abnormal number of chromosomes 2.
• Mosaic embryos contain a mixture of euploid and aneuploid cells, which can be detected through preimplantation genetic testing for aneuploidy (PGT-A) 3, 4.
• The prevalence of mosaicism in IVF blastocysts has been reported to be around 13.9% in one study, with segmental mosaicism being more common than whole-chromosome mosaicism 5.

Pregnancy Outcomes

• Transferring euploid embryos results in higher pregnancy rates and lower miscarriage rates compared to transferring aneuploid embryos 2.
• Mosaic embryo transfer (MET) has been reported to have reassuring outcomes, with over 100 live births documented and no abnormal phenotypes observed 3.
• However, the positive predictive value of noninvasive prenatal testing (NIPT) is altered in women who conceive through IVF with PGT-A, and positive test results should be interpreted with caution 6.

Factors Influencing Mosaicism

• Paternal age has been shown to be positively associated with mosaicism, with a higher risk of mosaicism observed in older fathers 5.
• Other factors such as maternal age, antral follicle count, and sperm concentration do not appear to be significantly associated with mosaicism 5.
• The use of intracytoplasmic sperm injection (ICSI) may be preferable to conventional insemination to minimize the rate of mosaicism in NGS PGT-A cycles 4.