Within in vitro fertilization (IVF), a “mosaic embryo” contains a mixture of cells with different chromosomal compositions. Understanding mosaicism is increasingly relevant in fertility treatments, offering a nuanced view beyond simple normal or abnormal classifications.
Understanding Mosaicism in Embryos
A mosaic embryo contains a blend of cells: some possess the correct number of chromosomes (euploid cells), while others have an abnormal number (aneuploid cells). This differs from a fully euploid embryo, where all cells have the expected 46 chromosomes, or a fully aneuploid embryo, where all cells carry an incorrect chromosome count, such as an extra chromosome (trisomy) or a missing one (monosomy).
The proportion of normal and abnormal cells varies significantly. Low-level mosaic embryos have a smaller percentage of abnormal cells (typically 20-40%), while high-level mosaic embryos contain a larger proportion (often 40-80%). This distinction is important because the level of mosaicism can influence an embryo’s potential for development. Mosaicism reflects a gray area in embryo classification, sitting between the clear-cut categories of euploid and aneuploid.
Formation and Identification of Mosaic Embryos
Mosaic embryos typically arise from post-zygotic mitotic errors during cell division after fertilization. As the embryo develops and its cells rapidly divide, a mistake in chromosome segregation can lead to some cells having an incorrect number of chromosomes, while others remain chromosomally normal. Errors occurring early in development might affect a larger proportion of cells, potentially leading to high-level mosaicism, whereas later errors may result in a lower percentage.
In an IVF setting, mosaic embryos are identified through Preimplantation Genetic Testing for Aneuploidy (PGT-A). This testing involves taking a small sample of 5 to 10 cells from the trophectoderm, the outer layer of the embryo that will eventually form the placenta. PGT-A is a screening test, not a diagnostic one, providing a likelihood of chromosomal anomalies rather than a definitive diagnosis for the entire embryo.
A limitation of PGT-A is that the biopsy only samples a few cells from the trophectoderm, which may not perfectly represent the chromosomal composition of the inner cell mass that develops into the fetus. The accuracy of PGT-A in detecting mosaicism can vary, and there is a possibility that a mosaic result for the biopsied cells does not fully reflect the whole embryo. Some studies suggest that the technical limitations of PGT-A can lead to an overestimation of mosaicism, identifying embryos as mosaic that might be entirely euploid or aneuploid.
Clinical Outcomes and Considerations for Transfer
Transferring mosaic embryos can lead to varying clinical outcomes. Many mosaic embryo transfers have resulted in healthy live births, providing reassurance for patients who may not have euploid embryos available. However, compared to euploid embryos, mosaic embryos generally show a lower rate of implantation and a higher risk of miscarriage. For instance, one study found a live birth rate of 46.6% for mosaic embryos compared to 59.1% for euploid embryos, while another reported a 30.8% live birth rate for mosaic embryos versus 46.6% for euploid embryos.
The degree and type of mosaicism can influence these outcomes. Low-level mosaic embryos, with a smaller percentage of abnormal cells, tend to have better outcomes than high-level mosaic embryos. Some research indicates low-level mosaic embryos can have live birth rates approaching those of euploid embryos. For example, a study noted that low-grade mosaics (less than 50% abnormal cells) had a 42.2% live birth rate, which was close to the 46.6% for euploid embryos. High-level mosaic embryos, with more than 50% aneuploid cells, demonstrate significantly lower live birth rates.
Despite the potential for a healthy live birth, overall rates of ongoing pregnancy and live birth are generally lower for mosaic embryo transfers compared to euploid embryo transfers, while miscarriage rates are higher. A meta-analysis indicated that mosaic embryo transfers resulted in a lower ongoing/live birth rate (27.1%) and a higher miscarriage rate (33.3%) compared to euploid transfers (47.0% and 20.5%, respectively). Importantly, studies have shown that babies born from mosaic embryo transfers typically do not exhibit evidence of mosaicism at birth.
Navigating Decisions with Mosaic Embryos
Decisions surrounding the transfer of mosaic embryos are often intricate and highly personal. Fertility specialists and genetic counselors play a significant role in guiding patients through these complex considerations. They interpret PGT-A results, explaining the specific type and percentage of mosaicism present in an embryo. Patients learn how the particular chromosomal abnormality might affect potential outcomes, including implantation rates, miscarriage risk, and the likelihood of a healthy live birth.
Genetic counseling helps patients understand the nuances of mosaicism, including that biopsy results may not perfectly reflect the entire embryo. Discussions often include the potential for self-correction in mosaic embryos, where abnormal cells may be eliminated or pushed to the placenta, allowing for normal development of the fetus. Shared decision-making is central to this process, involving the patient’s individual circumstances, such as age, the number of available embryos, and personal values.