Can a pregnancy with Embryo Mosaicism (MOSAIC), specifically XY -22 (Monosomy 22, M: 50%) develop into a normal baby and result in a normal pregnancy?

From the Guidelines

Embryo MOSAICO XY -22(M:50%) has a significantly reduced chance of developing into a normal baby with a normal pregnancy due to the high risk of miscarriage or severe developmental issues associated with monosomy 22. This type of embryo has mosaic chromosomal abnormalities, specifically involving chromosome 22 and the sex chromosomes (X and Y), with approximately 50% of the cells affected. Mosaicism means some cells have normal chromosomes while others have abnormalities. The prognosis depends on which cells are affected and how they distribute during development. Some mosaic embryos can self-correct during development if the abnormal cells are eliminated or confined to tissues that won't affect the baby's development. However, monosomy 22 (missing a chromosome 22) is typically lethal, and if present in a significant portion of cells, would likely lead to miscarriage or severe developmental issues 1.

Key Considerations

• The 50% mosaicism level is concerning, as higher percentages of abnormal cells generally correlate with poorer outcomes.
• Genetic counseling is strongly recommended to understand the specific risks, and enhanced prenatal monitoring would be necessary if pregnancy occurs.
• The American College of Medical Genetics and Genomics (ACMG) recommends that noninvasive prenatal screening (NIPS) be offered to patients with a singleton gestation to screen for fetal chromosome abnormalities, including sex chromosome aneuploidies (SCAs) 1.
• However, the ACMG also notes that the screening performance of NIPS for SCAs can vary, and the positive predictive value (PPV) for monosomy X, for example, may be lower due to higher rates of placental mosaicism or maternal mosaicism 1.

Recommendations

• Genetic counseling is essential to understand the specific risks associated with Embryo MOSAICO XY -22(M:50%) and to discuss the potential outcomes and necessary prenatal monitoring.
• Enhanced prenatal monitoring would be necessary if pregnancy occurs to closely monitor the development of the fetus and to detect any potential complications early on.
• Consideration should be given to the potential for neurobehavioral differences related to sex chromosome aneuploidies, and patients should be referred to professionals who can provide an accurate depiction of the phenotype and discuss the most recent evidence of medical interventions that may mitigate some of those outcomes 1.

From the Research

Embryo Mosaicism and Pregnancy Outcome

The provided studies do not directly address the specific scenario of a pregnancy with Embryo Mosaicism (MOSAIC), specifically XY -22 (Monosomy 22, M: 50%) and its potential to develop into a normal baby. However, we can gather some insights from the available evidence:

• Confined Placental Mosaicism (CPM): Studies 2, 3 discuss the concept of CPM, where aneuploid cells are confined to the placenta and do not affect the fetus. This condition can be associated with adverse pregnancy outcomes, such as intrauterine growth restriction (IUGR) and preterm birth.
• Mosaicism and Fetal Outcome: The study 4 reports a case of low-level mosaic trisomy 2 at amniocentesis, which was associated with a favorable fetal outcome. This suggests that the presence of mosaicism does not always lead to adverse outcomes.
• Non-Invasive Prenatal Testing (NIPT): Studies 5, 6 discuss the use of NIPT for detecting chromosomal abnormalities. While NIPT is highly sensitive and specific, it has limitations, such as the potential for false positives and the inability to detect CPM.

Key Points to Consider

• The presence of mosaicism in a pregnancy does not always lead to adverse outcomes.
• CPM can be associated with adverse pregnancy outcomes, but the fetus may not be affected.
• NIPT is a useful tool for detecting chromosomal abnormalities, but it has limitations and should be used in conjunction with other diagnostic methods.

Factors Influencing Pregnancy Outcome

• Level of Mosaicism: The level of mosaicism may influence the pregnancy outcome, with higher levels potentially leading to more severe adverse outcomes.
• Type of Mosaicism: The type of mosaicism, such as trisomy or monosomy, may also impact the pregnancy outcome.
• Presence of CPM: The presence of CPM can increase the risk of adverse pregnancy outcomes, such as IUGR and preterm birth.