An embryo is a developing organism formed by the fusion of an egg and sperm. Genetic instructions are organized into chromosomes; humans typically have 46 chromosomes arranged in 23 pairs, with one set coming from each parent. An aneuploid embryo possesses an abnormal number of these chromosomes—either too many or too few. This chromosomal imbalance significantly impacts the embryo’s ability to develop, implant, and progress through a successful pregnancy.
Defining Aneuploidy
Aneuploidy is a chromosome count that deviates from the normal human complement of 46 chromosomes. The two primary forms are Trisomy and Monosomy. Trisomy occurs when a cell has an extra copy of a specific chromosome, resulting in 47 chromosomes (e.g., Trisomy 21). Conversely, Monosomy describes the absence of one chromosome from a pair, leaving the cell with only 45 total chromosomes.
This error most often originates during meiosis, the process that creates egg or sperm cells. The mechanism is known as nondisjunction, which is the failure of chromosomes to separate correctly during cell division. When homologous chromosomes or sister chromatids fail to pull apart, the resulting gamete has an incorrect number of chromosomes. If this abnormal gamete participates in fertilization, the resulting embryo will be aneuploid.
Maternal Age and Aneuploidy Risk
The risk of an embryo being aneuploid is strongly correlated with the age of the mother. As a woman ages, the quality of her egg cells (oocytes) gradually declines, increasing the likelihood of errors during meiosis and leading to higher rates of nondisjunction.
Egg cells are particularly susceptible because they begin meiosis before birth but pause until ovulation. This prolonged pause is thought to contribute to the deterioration of the cellular machinery responsible for accurate chromosome separation. For example, the rate of aneuploidy in women undergoing IVF increases significantly with age, rising from about 30% at age 31 to potentially 89% by age 44.
Potential Outcomes of Aneuploidy
The vast majority of aneuploidies are incompatible with sustained development. In most cases, an aneuploid embryo will fail to implant in the uterus or result in a first-trimester miscarriage. Chromosome abnormalities are the most common cause of implantation failure and pregnancy loss, affecting nearly half of all first-trimester miscarriages.
Only a few specific aneuploidies allow for the possibility of a live birth, limited to Trisomy 21, Trisomy 18, and Trisomy 13. Trisomy 21 (Down syndrome) is the most common viable condition, while Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) are much more severe. The majority of fetuses with Trisomy 18 do not survive to term, and less than 10% of infants with this condition survive past their first year due to severe congenital defects.
Understanding Mosaic Embryos
A mosaic embryo contains two or more distinct populations of cells: some are chromosomally normal (euploid), while others are aneuploid. This condition typically arises from an error in cell division that occurs after fertilization, during the initial mitotic divisions of the developing embryo, rather than during the formation of the egg or sperm.
The presence of both normal and abnormal cells makes the clinical outcome of a mosaic embryo less certain. Mosaic embryos have a lower implantation rate and a higher miscarriage risk compared to fully normal embryos. However, a mosaic embryo can sometimes self-correct by eliminating the abnormal cells through apoptosis or by the preferential growth of the normal cell line, occasionally allowing for the development of a healthy fetus.