How does PGT-SR actually work?

[Anonymous]

How does PGT-SR actually work — how does the laboratory detect a chromosome imbalance in an embryo?

[Genetic Counselor]

Because this test is built around one family’s specific rearrangement, some preparatory work is usually needed before an in vitro fertilization cycle can proceed. The laboratory typically requests a blood sample from the carrier parent in advance to confirm the exact chromosomes and breakpoints involved, which allows the correct testing platform to be selected and, where needed, custom-designed for that rearrangement.

The couple then proceeds through a standard in vitro fertilization cycle:
• Ovarian stimulation and egg retrieval: hormone medications help the ovaries produce multiple eggs, which are then collected in a minor procedure.
• Fertilization: eggs are fertilized in the laboratory, usually with a technique called intracytoplasmic sperm injection, in which a single sperm is injected directly into an egg.
• Growth to the blastocyst stage: embryos are cultured for five to six days until they reach a stage with an outer layer, called the trophectoderm, and an inner cluster of cells that goes on to form the baby.
• Biopsy: a small number of cells are gently removed from the outer trophectoderm layer only, and the embryo is frozen while those cells are sent for genetic analysis.

The genetic analysis itself can use one of several laboratory methods, and the choice of method matters for what the result can and cannot tell a couple:
• Fluorescence in situ hybridization: an older technique using fluorescent probes targeted to the specific chromosome regions involved in the rearrangement; it can detect an imbalance but cannot tell a chromosomally normal embryo apart from one carrying the same balanced rearrangement as the parent.
• Array comparative genomic hybridization: measures the amount of genetic material across the genome to flag extra or missing segments, typically detecting imbalances above roughly 5 to 10 million base pairs; like fluorescence in situ hybridization, it cannot distinguish a normal embryo from a balanced-carrier embryo.
• Single nucleotide polymorphism array with haplotype analysis: tracks inherited patterns of genetic markers alongside the rearrangement, which uniquely allows the laboratory to tell a chromosomally normal embryo apart from one that is a balanced carrier like the parent, in addition to detecting unbalanced embryos.
• Next-generation sequencing: offers finer resolution and better sensitivity for detecting mosaicism, a state in which a mix of normal and abnormal cells is present within the same embryo biopsy.

Once results are available, an embryo classified as chromosomally balanced, whether fully normal or carrying the parent’s balanced rearrangement without gaining or losing material, is prioritized for transfer in a later cycle.

[Author]

Posts