Comprehensive Chromosomal Screening
It is no secret that in many IVF cycles , the transfer of apparently nice looking embryos will fail to result in a pregnancy or a live birth. There is a substantial amount of evidence that points to the likelihood that most of these failures are due to chromosome abnormalities in the embryos. Even in apparently normal healthy couples, a high percentage of embryos will not have the correct number of chromosomes. It has been thought that if abnormal embryos could be identified and then not used to attempt pregnancy, that the chance for a healthy live birth would be increased.
What is the correct number of chromosomes in an embryo?
Normal embryos should have 46 chromosomes arranged in 23 pairs. There should be two copies of chromosome #1 and two copies of chromosome #2 and so on. The 23rd pair of chromosomes are known as the sex chromosomes. These are the two chromosomes responsible for determining the gender of the individual. If there are two “X” chromosomes, the embryo will develop into a female. If there is one “X” and one “Y” chromosome, the embryo will develop into a male.
How many chromosomes can be tested?
In the early 1990s, we developed a technique known as preimplantation genetic diagnosis (PGD) to “count” the number of chromosomes in an embryo. PGD in those days relied on a technology known as fluorescent in-situ hybridization or FISH to count chromosomes. PGD with FISH allowed us to looked at 8 to 9 chromosome pairs.
Today, newer technologies such as Next Generation Sequencing (NGS) allow us to test all 23 pairs of chromosomes in an embryo. This is known as comprehensive chromosomal screening (CCS) or preimplantation genetic testing (PGT).
How does comprehensive chromosome screening work?
To look at the chromosomes in an embryo, it is necessary to remove one or more cells from the embryo. This is called an embryo biopsy. In the past, embryo biopsies were performed at a variety of different stage. Currently, the most common method for biopsying an embryo is to wait until it reaches the blastocyst stage (see below).
CCS with polar body biopsy
One option for couples, which was common in the past, is to remove two tiny cells that are normally disposed of by the embryo just after fertilization. These cells are called polar bodies. It is possible to do comprehensive chromosome screening on polar bodies. The main advantage of CCS with polar body biopsy is that results can be obtained in time to transfer the embryos at the normal time. No embryo freezing is required. The main disadvantage is that the polar bodies only give us information about embryo abnormalities that originated in the egg prior to fertilization. Recent data (2011) indicates that between 10-30% of chromosome abnormalities in an embryo may be missed by polar body testing. This means that is the CCS result is normal, that there is a 10-30% chance of abnormality being missed. Another disadvantage of CCS with polar body biopsy is that it is impossible to determine the gender of the embryos since gender is determined by the sperm chromosomes. Many babies have been born using polar body biopsy and CCS. However, it is no longer the recommended method for embryo biopsy.
CCS with blastomere biopsy
On the 3rd day of embryo development, most normal embryos should have divided into 8 cells or blastomeres. Biopsying one blastomere and performing comprehensive chromosome screening can also be performed. Blastomere biopsy is no longer performed since data emerged that the chance for implantation after biopsying an embryo at this stage was reduced.
CCS with trophoblast biopsy
By the 5th or 6th day of embryo development, a small percentage of the embryos should have reached the blastocyst stage. A blastocyst is an embryo which has divided into about 100 cells and has separated into two cell types. The inner cell mass is a small group of cells that will go on to form the fetus and should not be disturbed. This makes up about 5% of the blastocyst. The remaining 95% forms a fluid filled sphere and are called trophoblast cells. Trophoblast cells go on to make the placenta and all the other tissues except for the fetus. Trophoblast cells can be biopsied without affecting the development of the embryo. A 2011 study found NO ADVERSE EFFECTS of biopsy at the trophoblast stage.
Since many trophoblast cells can be removed, the results are going to be more accurate than either polar body or blastomere cells. Since only a portion of the embryos have the ability to reach the blastocyst stage, we don’t have to waste time or resources testing embryos that would not have developed anyway.
The combination of trophoblast biopsy, embryos freezing and PGT using Next Generation Sequencing is a powerful method of embryo selection and the chance for embryo implantation and delivery of a child is improved in patients over the age of 35. This is now the current recommended method for CCS at IVF1.
New techniques for evaluating embryos in IVF cycles are emerging. Next Generation Sequencing (NGS) is allowing us to assess embryos for abnormal numbers of chromosomes more quickly and for lower cost then we have been able to do in the past. Embryos that have reached the expanded blastocyst stage and have normal chromosomes by CCS have a very higher potential to produce a baby in older patients.