Embryo biopsy is a micro-surgical procedure performed during In Vitro Fertilization (IVF) that serves as the initial step for Preimplantation Genetic Testing (PGT). The technique involves the careful removal of a small collection of cells from an early-stage embryo developed in the laboratory. This sample of cells contains the embryo’s genetic material, which is then sent for analysis. The primary goal of this intervention is to screen the embryo for specific chromosomal abnormalities or single-gene disorders before it is transferred into the uterus.
The Purpose of Embryo Biopsy
Embryo biopsy is necessary for Preimplantation Genetic Testing, which helps increase the likelihood of a successful pregnancy and a healthy live birth. The procedure allows specialists to examine the embryo’s genetic makeup without disturbing the cells that will ultimately form the fetus. This screening is broadly categorized into three types, each focusing on a different genetic concern.
Preimplantation Genetic Testing for Aneuploidy (PGT-A)
Preimplantation Genetic Testing for Aneuploidy (PGT-A) is the most common form of testing and focuses on identifying embryos with an incorrect number of chromosomes, known as aneuploidy. Embryos with missing or extra chromosomes, such as those that cause Down syndrome, are a cause of implantation failure and miscarriage. PGT-A is often recommended for women of advanced maternal age or those with a history of recurrent pregnancy loss.
Preimplantation Genetic Testing for Monogenic Disorders (PGT-M)
Preimplantation Genetic Testing for Monogenic Disorders (PGT-M) is used when there is a known risk of a specific single-gene defect being passed down from the parents. This test screens for conditions like cystic fibrosis, sickle cell anemia, or Huntington’s disease, which are caused by a mutation in a single gene. A unique test, or “probe,” is often customized for each family’s specific genetic mutation before the IVF cycle begins.
Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR)
Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR) is utilized when one or both parents carry a structural abnormality in their chromosomes, such as a translocation or inversion. These rearrangements can lead to the embryo having missing or excess genetic material, which can result in recurrent miscarriages or a child with severe health issues.
The Physical Biopsy Procedure
The removal of the cells is a micro-manipulation performed by an embryologist under a specialized microscope. The procedure is almost always performed when the embryo has developed to the blastocyst stage, which typically occurs on Day 5 or Day 6 after fertilization. At this stage, the embryo is composed of two distinct cell groups: the inner cell mass (ICM), which will form the baby, and the trophectoderm (TE), which will form the placenta.
The embryologist extracts cells from the trophectoderm layer, ensuring the inner cell mass remains untouched. To access the trophectoderm cells, a small opening is created in the zona pellucida, the embryo’s outer shell, often using a precise, non-contact laser pulse. A fine biopsy pipette is then gently introduced through this opening to aspirate a small cluster of cells.
The goal is to remove approximately five to ten trophectoderm cells, which is a sufficient sample size for genetic analysis without compromising the embryo’s viability. The cells are separated from the rest of the embryo using a final, carefully placed laser pulse or a mechanical shearing motion, often referred to as “flicking.” Once the sample is secured, the biopsied cells are packaged in a sterile tube and prepared for shipment to the genetic testing laboratory.
Genetic Analysis and Reporting
After the trophectoderm cells are successfully biopsied, they are transported to a specialized lab for genetic analysis. The small sample of five to ten cells contains DNA, which is not enough for direct testing. Therefore, the first step is Whole Genome Amplification (WGA), a process that creates millions of copies of the DNA to provide a sufficient sample.
Modern genetic analysis utilizes Next-Generation Sequencing (NGS) technology to examine the amplified DNA. NGS provides a high-resolution view of the embryo’s chromosomal set. This technology can detect numerical abnormalities, single-gene mutations, and complex structural changes, depending on the type of PGT requested.
The genetic laboratory typically provides results within a week to ten days, allowing the fertility clinic to proceed with embryo selection. The results are classified into several categories: euploid, meaning the correct number of chromosomes; aneuploid, indicating an abnormal number of chromosomes; or mosaic, which suggests the presence of both normal and abnormal cells within the trophectoderm sample. These results are then used by the physician to determine which embryos are suitable for transfer.
Embryo Safety and Outcomes
The modern technique of trophectoderm biopsy, when executed by an embryologist, has a high success rate and is considered safe for the embryo. Biopsy at the blastocyst stage, removing cells from the pre-placenta, minimizes the impact on the inner cell mass.
Immediately following the biopsy, the embryo is cryopreserved, or flash-frozen, using a technique called vitrification, while awaiting the genetic results. The survival rates of embryos after this biopsy and subsequent freezing/thawing process are high and comparable to those of non-biopsied embryos undergoing the same cryopreservation. This freeze-all approach allows time for the genetic analysis and ensures the embryo is transferred into a uterus prepared in a cycle separate from the stimulation phase.
The procedure has not been shown to compromise the embryo’s developmental potential, as it targets the trophectoderm, a cell lineage separate from the one that forms the baby. The use of PGT following a successful biopsy is linked to higher implantation rates per transfer and a lower risk of miscarriage because it allows for the selection of the most chromosomally normal embryos.