Embryo Biopsy & PGT Genetic Testing

Endometrial Biopsy

An endometrial biopsy is done to evaluate the development of the lining of the uterus (endometrium) in relationship to ovulation. Routinely performed 7-10 days after a positive LH surge test, this test determines if the lining of the uterus is developing at the expected rate. Because a catheter is inserted into the uterus and a sample of the uterine lining is obtained, it is extremely important that you are not pregnant: this procedure has a 5% chance of disrupting an early pregnancy. It for this reason that you have been advised to avoid or have only protected intercourse during this cycle.

To help minimize the discomfort associated with the procedure, we suggest you take two Aleve (440-550mg) or three to four Motrin/Advil/Nuprin (ibuprofen 600-800mg) one hour before the biopsy. Just prior to the biopsy, a topical anesthetic may be applied to the cervix followed by cleansing with an iodine-based solution. If you are allergic to novocaine, betadine, iodine, or shellfish, please notify the doctor prior to the procedure. Once the anesthetic has had time to become effective, an instrument is placed on the cervix to hold it in place while a small plastic tube (catheter) is inserted through the cervical canal and into the uterus. It is normal to experience moderate to severe menstrual-like cramps when the catheter enters the uterus and while the biopsy is being taken, but this usually takes no more than 10-15 seconds.

Once the catheter is removed, the cramping resolves quickly. If the adequate tissue has been obtained, the procedure is complete. We advise you to avoid intercourse for two days after the procedure and call us if you experience any excessive or prolonged bleeding, temperature in excess of 100.6 degrees, pulse rate greater than 100 or excessive or prolonged pain.

Preimplantation Genetic Testing

What is preimplantation genetic testing?

Preimplantation genetic testing (PGT) is a technique used in IVF to test for genetic abnormalities in your embryos. PGT involves performing embryo biopsy of day 5 or 6 blastocysts before they are transferred back to the uterus. The goal of PGT is to reduce the risk of transferring an abnormal embryo which may result in a failed embryo transfer, biochemical pregnancy, miscarriage, fetal death or a child born with anomalies.

Types of PGT 

There are different types of PGT:

1. Preimplantation genetic testing for aneuploidy (PGT-A)

A normal human embryo contains 23 pairs of chromosomes, one pair from the egg and one pair from sperm. Unfortunately, not all of our eggs and sperm have a normal number of chromosomes (termed euploid). Having embryos with extra or missing chromosomes, known as aneuploidy, happens by chance and is the most common cause of pregnancy loss. Aneuploid embryos may also result in an infant born with various anomalies. PGT-A involves testing the embryos for the correct number of chromosomes to maximize your chance of a healthy pregnancy

2. Preimplantation genetic testing for monogenic disorders (PGT-M)

Many diseases involve a single gene defect (or monogenic defect) that is passed on from the parents. Parents known to be carriers of a genetic mutation that can be inherited can test their embryos to reduce the risk of having an affected child through a process known as PGT-M, formerly known as PGD (preimplantation genetic diagnosis).

Common examples for the need to use PGT-M includes:

• Both parents are silent carriers of an autosomal recessive disease, where two copies of the mutation are inherited (one from each parent) resulting in a diseased child (eg. Cystic fibrosis, sickle cell anemia, spinal muscular atrophy). Parent carrier status is often discovered during routine genetic carrier screening, prior to IVF, or through family history.
• Being a carrier of an X-linked disease, where the mutation is passed on from the X chromosome (eg. Fragile X syndrome).
• Presence of an autosomal dominant condition in one parent (ex. Huntington disease). This will yield a 50% chance of having an affected child.
• Parents with previous child affected by a single gene disorder
• One parent has a mutation associated with hereditary cancer syndrome (eg. BRCA1/2, Lynch syndrome)

3. Preimplantation genetic testing for structural rearrangements (PGT-SR)

This type of testing is for patients who are known to have a rearrangement of their own chromosomes. For example, with a reciprocal translocation, a piece of a chromosome breaks off and reattaches another chromosome, resulting in no net loss or gain of genetic material for the parent but may result in a loss or gain of genetic material for the embryo. Classic clinical presentation of someone with a chromosomal translocation or inversion is a history of recurrent pregnancy loss, which is diagnosed by performing parental karyotype(s). Embryos that have an extra or missing piece of a chromosome have a higher risk of miscarriage or a child born with disabilities.

Candidates for PGT

PGT can only be performed during an IVF cycle. The decision to proceed with PGT can be fairly complex and will require significant counseling. Generally speaking, couples with a history of recurrent pregnancy loss, failed IVF cycles, advanced maternal age (>35 years old), or a prior pregnancy or child affected by a chromosomal or single gene defect.

How is PGT performed?

Step 1. Patients undergo IVF starting with ovarian stimulation (unless using donor eggs). After the egg retrieval, mature eggs are fertilized using your partner’s sperm (or donor sperm) in a process known as intracytoplasmic sperm injection [link for ICSI tab inserted] (ICSI).

ICSI is necessary prior to perform PGT to reduce the risk of contamination that may occur from other surrounding sperm in the petri dish during conventional IVF. This helps to maximize accuracy of the genetic testing

Step 2. The embryos are cultured in the lab and monitored over a period of 5-6 days, until the cells have divided enough to form a blastocyst (consists of approximately 70-100 cells). The blastocyst comprises an outer layer of cells known as the trophectoderm which will eventually develop into the placenta and an inner cell mass which will become the fetus. A trained embryologist will biopsy 5-10 cells from the trophectoderm and transfer the sample to an outside facility for analysis.

Step 3. The embryos are frozen while awaiting results. Results are usually available after 7-10 days.

Step 4. One euploid embryo is selected at a time for transfer back into the uterus.

Step 5. Aneuploid or abnormal embryos are either discarded or donated for research (with your consent).