PGD / PGT for miscarriage

Preimplantation genetic diagnosis (PGD) – now referred to as Preimplantation Genetic Testing (PGT) is a method used to identify genetic and chromosomal abnormalities in embryos. There are many potential applications for PGD / PGT in the field of reproductive medicine. One of the most exciting uses for PGD / PGT is the ability to decrease the rate of miscarriage.

Miscarriage due to chromosome abnormalities

The vast majority of miscarriages are due to abnormalities in the number of chromosomes contained in the embryo. Many of these are currently detectable by PGT. The biologic process by which embryos receive their chromosomes is complex. Prior to ovulation, an egg has two extra sets of chromosomes. At the time of ovulation, one set of chromosomes is pushed out of the egg into a tiny cell called the first polar body. In an IVF cycle, this occurs when a woman takes the hCG trigger injection. At the time of fertilization, the second extra set of chromosomes is pushed out into the second polar body. This second extra set of chromosomes is essentially replaced by the chromosomes contained in the sperm. When fertilization is completed, therefore, the egg should have contributed one set of 23 chromosomes and the sperm should have contributed one set of 23 chromosomes. Thus, an embryo that contains 23 pairs of chromosomes, for a total of 46, is considered normal or euploid.

Unfortunately, during this complicated process, occasionally an embryo will lose or gain one or more chromosomes. These embryos are abnormal and are called aneuploid. Certain chromosomes seem to be more prone to gain or loss. So for example, embryos with extra copies of chromosomes 13, 18 or 21 occur much more commonly than embryos with extra chromosomes 1, 2 or 3.

PGD miscarriage TrisomyIf an embryo contains an extra or missing chromosome in all of its cells, there are only three possible outcomes for that embryo. Most of these aneuploid, abnormal embryos will never implant into the uterus and produce a pregnancy. If the abnormal embryo does implant, the majority will be lost during the early portion of the pregnancy. This is the most common cause of miscarriage in human beings. If an abnormal embryo does not miscarry, the baby born will have birth defects. One of the most well known birth defects is when an extra copy of chromosome 21 is contained in the embryo. These babies are born with a disorder called Down’s syndrome.

As women age, the percentage of embryos with chromosomal abnormalities increases. This is the primary reason why older women have lower fertility rates, higher miscarriage rates and higher rates of birth defects.

Currently, there is no known method to prevent embryos from developing these chromosome abnormalities. PGD / PGT can be used, however, to detect embryos with these abnormalities before they are placed into the uterus.

Preimplantation Genetic Testing

The PGT method most commonly used to detect the number of chromosomes in an embryo is called Next Generation Sequencing (NGS). This is a rapid and highly efficient technique for accurately determining the number of chromosomes.

Next Generation Sequencing for PGD
Next Generation Sequencing showing an embryo with a missing chromosome

PGT for miscarriage

The couples who are at highest risk for chromosome abnormalities and miscarriages include those in whom the female is older. In fact, the older the female, the higher the rate of abnormalities found and the higher the miscarriage rate. Others at high risk include couples who have had recurrent miscarriage.

PGT for recurrent miscarriage

In 4-5% of couples with recurrent miscarriage, either the male or female has a structural abnormality involving two of their chromosomes known as a translocation. A translocation involves breakage of two chromosomes with the pieces going to the other chromosome. For example, a 13:21 translocation means that a small bit of chromosome 13 is attached to chromosome 21 and a small piece of chromosome 21 is attached to chromosome 13. The individual who carries a translocation may be completely unaffected because the total amount of DNA is normal. This is called a balanced translocation.

However, if a translocation carrier tries to reproduce, the embryos produced may have too much or too little DNA. This is called an unbalanced translocation and will lead to miscarriage.

PGT can be used to detect translocations in embryos.

Next Generation Sequencing showing a translocation in an embryo

In studies of couples with recurrent miscarriage that have a translocation, the risk of miscarriage was reduced by over 90%.