An aneuploid embryo possesses an incorrect number of chromosomes, the structures within cells that carry genetic information. Humans typically have 46 chromosomes, arranged in 23 pairs, with one set inherited from each biological parent. A euploid embryo, in contrast, contains the correct count of 46 chromosomes and is considered genetically normal. Aneuploidy is a common topic in fertility medicine, as it can affect the potential for a successful pregnancy.
The Genetic Basis of Aneuploidy
Chromosomes carry the genetic instructions for building and operating a human body. Each cell normally contains 23 pairs of these chromosomes. Most instances of aneuploidy arise from random errors during meiosis, the specialized cell division process that produces eggs and sperm. During meiosis I or II, chromosomes or their sister chromatids may fail to separate properly, a phenomenon called non-disjunction.
These errors are generally not attributed to anything parents did or did not do. A significant factor influencing aneuploidy is advanced maternal age. As women age, the likelihood of errors during egg development increases; more than half of oocytes from women over 35 years may be aneuploid. By age 40, approximately 70% of eggs may be abnormal. This age-related increase in meiotic errors is a primary reason for the higher incidence of aneuploidy in embryos from older women.
Detection Through Genetic Testing
Aneuploid embryos are primarily identified through Preimplantation Genetic Testing for Aneuploidy (PGT-A), typically performed on embryos created during an in vitro fertilization (IVF) cycle. During PGT-A, a small number of cells (3 to 10) are carefully removed from the trophectoderm, the outer layer of a developing embryo. This biopsy usually occurs when the embryo reaches the blastocyst stage, around day 5 or 6 of development.
The biopsied cells are sent to a specialized genetics laboratory for analysis. The laboratory screens all 23 pairs of chromosomes to determine if the correct number is present. PGT-A aims to identify euploid embryos for transfer, improving the chances of a successful pregnancy and reducing the risk of adverse outcomes.
Outcomes of Aneuploid Embryos
When an embryo is identified as aneuploid, there are several possible outcomes, most of which are incompatible with a healthy, ongoing pregnancy. The most frequent outcome for aneuploid embryos is implantation failure. This means the embryo does not successfully attach to the uterine wall, preventing the initiation of a pregnancy. Aneuploidy is considered a leading cause of such failures.
Another common outcome is early pregnancy loss, or miscarriage. The genetic imbalance within an aneuploid embryo is often too severe for sustained development, leading the pregnancy to end spontaneously. A significant proportion of miscarriages, potentially up to 76% in the first trimester, are linked to aneuploidy. While less common, some aneuploidies can result in a live birth with a chromosomal condition. A well-known example is Trisomy 21, also known as Down syndrome, which occurs when an embryo has an extra copy of chromosome 21.
Understanding Mosaic Embryos
A mosaic embryo, identified through genetic testing, contains a mixture of both chromosomally normal (euploid) and abnormal (aneuploid) cells. This differs from a fully aneuploid embryo, where all tested cells are abnormal due to errors typically originating in the egg or sperm. Mosaicism means the embryo is neither entirely normal nor entirely abnormal.
Mosaicism commonly arises from errors that occur after fertilization, during the early cell divisions of the embryo. The proportion of normal versus abnormal cells can vary, often categorized as low-level (e.g., 20-40% abnormal cells) or high-level mosaicism (e.g., 40-80% abnormal cells). Research suggests that some mosaic embryos may possess a potential for “self-correction,” where abnormal cells either die off or are shunted to the part of the embryo that forms the placenta, allowing euploid cells to predominate in the developing fetus.
Clinical Decisions and Considerations
When genetic testing results are available, fertility treatment prioritizes the transfer of euploid embryos, which offer the highest likelihood of successful implantation and a healthy live birth. However, the presence of mosaic embryos, or situations where no euploid embryos are available, can lead to complex decision-making for patients and their reproductive teams.
Clinicians consider various factors, including the specific chromosome(s) affected, the percentage of aneuploid cells, and the type of mosaicism (e.g., whole chromosome versus segmental). Some clinics may proceed with the transfer of mosaic embryos, particularly those with low-level mosaicism. This decision is made after counseling on the potential risks, which can include a higher chance of miscarriage compared to euploid embryos. This ensures patients are informed about their options and potential outcomes.