胚胎植入前基因检测信息

Preimplantation genetic testing (PGT) comprises a group of molecular diagnostic assays performed on embryos generated through in vitro fertilization (IVF) to assess genetic integrity prior to uterine transfer. PGT is used to evaluate chromosomal copy number, chromosomal structural integrity, and known pathogenic single-gene variants to support informed embryo selection and clinical decision-making.

PGT is routinely applied to help improve implantation rates, reduce miscarriage risk, and minimize transmission of inherited genetic disorders.

PGT-A: Aneuploidy Screening

PGT-A assesses whole-chromosome copy number across all 23 chromosome pairs, including autosomes and sex chromosomes. Aneuploid embryos are associated with lower IVF success rates, implantation failure, early pregnancy loss, and chromosomal syndromes.¹

PGT-SR: Structural Rearrangement Analysis

PGT-SR is indicated for patients with known chromosomal rearrangements (e.g., reciprocal or Robertsonian translocations, inversions). The assay detects unbalanced chromosomal content resulting from meiotic segregation errors.

PGT-M: Monogenic Disorder Testing

PGT-M is performed when a pathogenic or likely pathogenic variant is known within a family, typically involving single nucleotide variants (SNVs) or small insertions/deletions. Embryos are screened to identify non-carriers or unaffected carriers based on the inheritance model.²

Humans possess 46 chromosomes (22 autosomal pairs and one pair of sex chromosomes). Deviations in chromosomal number or structure can lead to abnormal embryonic development, miscarriage, or live-born genetic conditions such as trisomy 21 or monosomy X.

Based on PGT-A and PGT-SR results, embryos are classified as:

• Euploid: Normal chromosomal copy number and structure; generally prioritized for transfer.
• Aneuploid: One or more whole or segmental chromosomal abnormalities; typically excluded from transfer.
• Mosaic: Presence of two or more chromosomally distinct cell lines within the embryo. Transfer decisions are individualized based on the level and type of mosaicism, chromosomes involved, and availability of euploid embryos.

PGT is performed on biopsied embryonic cells, most commonly from the trophectoderm at the blastocyst stage. DNA is extracted from the sampled cells and subjected to downstream molecular analysis.³

Historical and Current Testing Technologies:

• FISH: Chromosomal enumeration or rearrangement detection
• PCR-based assays: Targeted detection of known single-gene variants

Limitations include low genomic resolution, restricted chromosome coverage, and reduced diagnostic accuracy.

Array Comparative Genomic Hybridization (aCGH)

aCGH enables genome-wide assessment of chromosomal gains and losses with improved resolution compared to FISH by comparing the sample to a reference genome but does not detect all forms of mosaicism or sequence-level variants.

Next-generation sequencing (NGS) is commonly used for preimplantation genetic testing due to its high analytical sensitivity, genomic resolution, scalability, and ability to integrate multiple testing modalities within a single workflow.

In NGS-based PGT, DNA is extracted from biopsied embryonic cells, most commonly trophectoderm cells at the blastocyst stage, and is subjected to whole-genome amplification (WGA) followed by massively parallel sequencing. Sequencing reads are aligned to a reference genome and analyzed using quantitative bioinformatic pipelines to assess chromosomal copy number and targeted sequence variants.

Detection Capabilities

NGS helps enable comprehensive genomic assessment, including:

• Whole-chromosome aneuploidy:
  Detection of gains or losses of entire chromosomes across all autosomes and sex chromosomes with high accuracy.
• Segmental aneuploidy:
  Identification of partial chromosomal gains or losses, typically at the megabase scale, which may be associated with unbalanced structural rearrangements or post-zygotic mitotic errors.
• Chromosomal structural imbalances:
  Detection of chromosomal translocations, inversions, and deletions when used in PGT-SR workflows resulting from unbalanced transfers of genetic material.
• Targeted monogenic variants (PGT-M):
  When combined with locus-specific enrichment or linkage-based analysis, NGS can help identify known pathogenic variants, including single nucleotide variants (SNVs) and small insertions/deletions, while simultaneously assessing chromosomal status.

Mosaicism Assessment

NGS provides a quantitative measurement of copy number variation, enabling estimation of the proportion of abnormal cells within a biopsy sample. This helps support classification of embryos as euploid, aneuploid, or mosaic based on defined thresholds and laboratory-validated algorithms.

Quantitative NGS data allows:

• Improved sensitivity for detecting low- to moderate-level mosaicism
• Differentiation between true biological mosaicism and technical artifacts
• More informed clinical decision-making regarding mosaic embryo transfer

Advantages Over Earlier Technologies

Compared to historically used methods such as FISH and aCGH, NGS-based PGT may offer:

• Higher genomic resolution and broader chromosomal coverage
• Increased sensitivity for segmental abnormalities
• Greater accuracy in mosaicism detection
• Faster turnaround times with batch processing
• Scalability and standardization across high-throughput IVF laboratories

Clinical Considerations

While NGS-based PGT provides robust genomic insight, results are influenced by factors such as biopsy quality, WGA performance, sequencing depth, and bioinformatic thresholds. As with all PGT modalities, findings should be interpreted in conjunction with clinical context and supported by genetic counseling.

 In reproductive medicine, PGT is used to:

• Increase chances of IVF success
• Improve embryo selection efficiency
• Reduce miscarriage rates, particularly in patients of advanced maternal age
• Decrease the likelihood of transferring embryos with pathogenic genetic abnormalities
• Shorten time to pregnancy
• Reduce the number of IVF cycles required to achieve a live birth

PGT functions as a risk stratification and prioritization tool rather than a diagnostic test of fetal health, and results should be interpreted within the context of clinical findings and genetic counseling.