Genetic aspects of miscarriage.

Area of Science:

• Reproductive genetics
• Fetal medicine
• Clinical cytogenetics

Background:

• Fetal chromosome abnormalities contribute significantly to first-trimester pregnancy loss.
• Numerical abnormalities are most common (86%), followed by structural abnormalities (6%) and mosaicism (8%).
• Recurrence risk for numerical abnormalities is low, limiting routine karyotyping of miscarriage tissue.

Purpose of the Study:

• To review the role of fetal chromosome abnormalities in early pregnancy loss.
• To discuss diagnostic techniques for identifying chromosomal abnormalities.
• To highlight the importance of parental carrier screening for structural abnormalities.

Main Methods:

• Review of conventional laboratory techniques: tissue culturing, karyotyping, chorionic villi sampling.
• Description of advanced techniques: fluorescence in situ hybridization (FISH), comparative genomic hybridization (CGH).
• Discussion of genetic mechanisms including single-gene defects, uniparental disomy, imprinting, and multifactorial disorders.

Main Results:

• Half of structural abnormalities may stem from parental balanced translocations or inversions.
• Parental carriership of balanced structural abnormalities is found in 4-6% of recurrent miscarriage cases.
• Inherited unbalanced structural abnormalities can lead to congenital malformations and intellectual disability.

Conclusions:

• Prenatal diagnosis is recommended for pregnancies where parental balanced structural chromosome abnormalities are identified.
• Further research is needed to clarify the role of other genetic mechanisms in miscarriage.
• Routine karyotyping of fetal material for numerical abnormalities in miscarriages may not be clinically indicated.