PGT-A Preimplantation Genetic Testing for Aneuploidies

PGT-A Preimplantation Genetic Testing for Aneuploidies

PGT-A (Preimplantation genetic testing for aneuploidies) is a genetic test to check the completion of 23 pairs of embryo chromosomes during IVF or ICSI procedures prior to transferring the embryo back into the uterus to achieve a successful pregnancy; the embryo is healthy, strong, and at low risk for genetic disorders such as Down syndrome, Turner syndrome, or Edwards syndrome (trisomy 18). PGT-A is appropriate for infertile couples, women who have experienced recurrent miscarriages from older pregnancies, or women who have failed IVF multiple times. PGT-A lowers the risk of miscarriage, reduces IVF/ICSI cycles, and increases the chance of a successful pregnancy outcome.

Why PGT-A?

Typically, human chromosomes consist of 23 pairs of chromosomes totaling 46 chromosomes, comprising 22 pairs of somatic chromosomes and 1 pair of sex chromosomes; female chromosomes are 22 + xx = 23 pairs and male chromosomes are 22+ xy= 23 pairs. If the number of chromosomes is complete or balanced, the condition is known as euploidy; if chromosomes are missing or extra to the normal chromosome number of 46 chromosomes, the condition is known as Aneuploidy, which is typically found in older pregnant women, which not only reduces the chance of an active pregnancy but also increases the risk of miscarriage, pregnancy of a fetus with Down syndrome or impaired intelligence, developmental delays, or Cri-du-chat syndrome with bodily organ abnormalities.

PGT-A screens for a full complement of 23 pairs, or 46 chromosomes, not missing or more than 23 pairs, which reduces the risk of miscarriage, lowers the chance of conceiving a Down syndrome baby and prevents the risk of passing on genetic diseases to the next generation. In addition, PGT-A, by selecting healthy embryos, increases the chance of pregnancy for older women, lowers the risk of recurrent miscarriages, and allows couples with abnormal chromosomes to have live-born, healthy babies.

Who can benefit from PGT-A?

• Women over the age of 35 desire to conceive and have a child.
• Women who have previously been pregnant with an abnormal chromosome.
• Women with a history of more than 2 miscarriages due to chromosomal abnormalities or unknown causes.
• Women or men with infertility who have failed more than 2 IVF cycle attempts.
• Women or men with a family history of chromosomal abnormalities.
• Couples who choose IVF/ICSI to have a child in order to reduce the risk of having a baby with Down syndrome or another genetic disorder.

What is the PGT-A procedure?

Trophectoderm Biopsy

The embryologist will culture embryos in the embryology laboratory until reaching the blastocyst stage, or approximately 5–6 days after the egg retrieval procedure. The reproductive endocrinologist will then collect 5–6 samples of trophectoderm epithelium, or the outer cells of the chromosomes that will form into a child’s placenta, to check for chromosomal abnormalities without harming the embryonic cells that will develop into a baby. During this time, the embryo will be kept frozen while waiting for the results of the trophectoderm biopsy.

Embryo Freezing

While the reproductive endocrinologist collects samples of trophectoderm epithelium, or chromosome outer cells, for genetic testing in the genetics laboratory, the embryologist will freeze the embryos. If the PGT-A results are normal and the mother's physical condition is appropriate for pregnancy, the reproductive endocrinologist will proceed with the frozen embryo transfer (FET) procedure, which involves thawing and transferring the embryo into the uterus for implantation and pregnancy.

Chromosomal Analysis

At the genetic laboratory, the genetic technician will examine samples of trophectoderm epithelium or placental cells to detect aneuploidy by counting the number of chromosomes to verify if all 23 pairs are complete, including checking the shape of chromosomes to see if there are any abnormalities, whether chromosomal aneuploidy or segmental chromosomal aneuploidy, and also checking the total number of chromosomes to see if they are missing or extra chromosomes from the normal 46 chromosomes number, and if so, how many chromosomes are missing or adding, as well as checking the gender chromosomes for both female chromosome xx and male chromosome xy.

Genetics Report

After completing the PGT-A analysis, the genetic technician will send the PGT-A report to the reproductive endocrinologist, who will summarize and inform the examinee about the embryo's chromosome status, indicating the number of chromosome pairs, the total number of chromosomes, and the completeness or shape of the chromosomes, including the sex chromosomes, to plan a personalized treatment plan suitable for each individual.

Embryo Selection and Frozen Embryo Transfer

Once the physical condition of the prospective mother is ready for pregnancy, the embryologist will select embryos with all 23 pairs of healthy chromosomes to thaw. The reproductive endocrinologist will then transfer the embryos into the uterus to achieve a full pregnancy. The remaining healthy embryos will be frozen as a backup in case a repeat embryo transfer procedure is needed in the coming cycles.

What does the PGT-A result mean?

The PGT-A results can be reported in 4 types:

1. Euploidy
   Normal: Embryo chromosomes consist of 23 pairs of chromosomes (for a total of 46 chromosomes) and are suitable for transfer into the uterus for pregnancy.
2. Aneuploidy
   Abnormal: Embryo chromosomes are missing, have extra chromosome numbers than the normal 46 chromosomes, or have an abnormal shape and are not suitable for transferring into the uterus for pregnancy.
3. Mosaic
   Mixed: Normal and abnormal embryo chromosomes are mixed. Some types of Mosaic chromosomes can transfer the embryo into the uterus for pregnancy. The reproductive endocrinologist will determine the ratio of normal and abnormal chromosomes. If the ratio of abnormal chromosomes is less than normal chromosomes and there is a high chance of conceiving a normal, healthy baby, the reproductive endocrinologist will decide whether to proceed with the embryo transfer procedure as a next step, depending on the doctor’s discretion.
4. No Result
   Inconclusive: The embryo chromosome results were inconclusive due to poor chromosome quality or an inadequate number of chromosomes for PGT-A. The reproductive endocrinologist will consider repeating PGT-A using the remaining frozen embryo in order to obtain conclusive results.

How long does it take for the PGT-A result?

Typically, PGT-A results will be available within 1-2 weeks, depending on each individual’s health condition. However, if an individual has a complex chromosomal disorder, a genetic technician may take an additional 2-4 weeks to process and summarize the test results.

What are the advantages of PGT-A?

• Increased Implantation Rates: Missing embryonic chromosomes is the most common cause of miscarriage in the first eight weeks of pregnancy. PGT-A aids in the selection of high-quality embryos with 23 pairs of normal-shaped chromosomes without missing or extra chromosomes from the normal 46 chromosomes, ensuring a safe and smooth pregnancy.
• Reduces Miscarriage Rates: The reproductive endocrinologist typically detects abnormal chromosomes or aneuploidy in up to 50% of older pregnant women, as well as eggs with a greater number of missing or extra chromosomes than the average young pregnant woman. PGT-A detects abnormal chromosomes, prevents the transmission of genetic diseases to the future child, and potentially lowers the risk of miscarriage.
• Reduce IVF/ICSI Cycles: PGT-A aids in achieving a successful IVF pregnancy in just one cycle (depending on the maternal health) by selecting only healthy chromosomes before transferring, significantly saving time and cost from repetitive IVF cycles and lowering the risk of conceiving a baby with genetic conditions that require postpartum, long-term treatment.
• Inform crucial health information: Prior to deciding to have a child, PGT-A provides crucial health information, such as healthy chromosomes that contribute to a healthy baby. With this benefit, those with perfect chromosomes can be privileged with PGT-A by receiving an initial consultation with an expert reproductive endocrinologist to plan for their future children.
• Improved Pregnancy Outcomes: PGT-A selects normal chromosomes for transfer into the maternal womb. Only healthy chromosomes will result in a healthy pregnancy and contribute to a quality pregnancy, particularly in the first trimester when the pregnancy is most vulnerable. When a pregnant mother has a healthy pregnancy, her chances of having a healthy baby free of genetic diseases increase even more.

What if a PGT-A ‘No Result’?

Typically, the results of the PGT-A 'No Result' are classified into 2 types:

1. Insufficient chromosomes or poor-quality embryo chromosomes: Embryos with insufficient chromosomes or poor-quality chromosomes typically fail to progress to the blastocyst stage (5–6 days after egg retrieval) and are insufficient for trophectoderm biopsy during the PGT-A. To proceed with the procedure, the reproductive endocrinologist may determine to repeat the ovulation stimulation process and collect new eggs with sufficient chromosome number and quality for the next PGT-A in order to gain the result.
2. Misinterpretation: PGT-A is a sampling of cells using only 5–6 chromosomes that will develop into the baby's placenta. As a result, there is a chance of incorrect interpretations, particularly in the case of mosaics, where normal and abnormal chromosomes have mixed. Misinterpretation may occur from trophectoderm biopsy if the samples consist of only cells with abnormal chromosomes, despite most cells having normal chromosomes. To confirm the PGT-A results, the reproductive endocrinologist will order a repeat trophectoderm biopsy.

How accurate is PGT-A?

PGT-A is a chromosome screening test or embryo grading with a high accuracy rate of up to 98%, allowing those with infertility, women over the age of 35, and those with a family history of chromosomal abnormalities to successfully conceive and have a baby.

What is the success rate of PGT-A?

According to a study of women who had undergone IVF or ICSI at various ages and compared those who had PGT-A before embryo transfer to those who did not, the success rates of PGT-A varied with age as follows:

1. Women under 35 with PGT-A had a 56.5% pregnancy rate. Those who did not get a PGT-A had a pregnancy rate of 48.1%.
2. Women aged 35–37 with PGT-A had a 54.2% pregnancy rate. Those who did not get a PGT-A had a pregnancy rate of 39.2%.
3. Women aged 38–40 with PGT-A had a 52.2% pregnancy rate. Those who did not get a PGT-A had a pregnancy rate of 27.6%.
4. Women aged 41–42 with PGT-A had a 46.7% pregnancy rate. Those who did not get a PGT-A had a pregnancy rate of 15.3%.
5. Women over 42 with PGT-A had a 42.4% pregnancy rate. Those who did not get a PGT-A had a pregnancy rate of 5%.

These findings also revealed that those undergoing IVF or ICSI who received PGT-A testing prior to transferring the embryos into the uterus had a 95% pregnancy success rate within 3 consecutive frozen embryo transfers.

PGT-A at MedPark Hospital

Fertility and Genetics Center at MedPark Hospital, Bangkok, Thailand, is led by a team of expert reproductive endocrinologist professors with extensive experience in performing reproductive medicine both nationally and internationally, who are ready to provide diagnostic and treatment for those with infertility through IVF and ICSI using PGT-A, PGT-M, or PGT-S prior to embryo transfer, utilizing state-of-the-art technology and equipment in the JCI standards embryology laboratory and the highest standard of care throughout every step of the journey to ensure the embryo is healthy, strong, and yields a quality pregnancy while providing comprehensive care for both the mother and the baby from prenatal to postpartum to ensure the mother is healthy, the baby has perfect physical development, free of complications, and can safely born, become a golden chain bonds all family members.