GENETICS 101

Chromosomes are small structures that contain all 20,000 of our genes, which produce the signals for the development and maintenance of the human body. Every cell in the human body needs to have a total of 46 chromosomes; 23 chromosomes that originally came from the egg and 23 chromosomes from the sperm. Both your chromosomes and genes play a vital role in conception and can impact the health of your baby. When chromosomal abnormalities or gene mutations occur, it may result in infertility, miscarriage or having a child with a genetic disease.

Fortunately, through advancements in reproductive genetics, cells from your embryos can be removed and screened with molecular techniques to determine which embryos are affected by chromosomal abnormalities and/or gene mutations. By only selecting and using the highest quality chromosomally normal embryos possible during the in vitro fertilization (IVF) process, it reduces the likelihood of implantation failure, miscarriage, and gives you the best chance of delivering a healthy baby.

YOUR RISK OF CHROMOSOMAL ABNORMALITIES

Maternal Age and Chromosomal Abnormalities

The most common chromosomal concern in a preimplantation embryo is aneuploidy – when the embryo has an incorrect number of chromosomes (gain or loss). Chromosomally abnormal embryos are unlikely to implant in the uterus or they will result in miscarriage or chromosomal disorders, such Down syndrome (extra copy of chromosome 21).

As a woman ages, she is more likely to have aneuploid embryos. At the age of 25, 75% of a woman’s eggs are chromosomally normal. At 35 years of age, about 50% of a woman’s eggs are chromosomally normal. By the time a woman reaches 40, about 10-15% of her eggs are chromosomally normal.

YOUR RISK OF INHERITED GENE MUTATIONS

Hereditary Genetic Disorders

Some diseases, such as cystic fibrosis and muscular dystrophy, are caused by single gene mutations that are inherited from the parents. If both parents are identified as carriers for a specific genetic disorder, their chance of having an affected child is 25%. This is called recessive inheritance. There is also dominant inheritance in which one parent has the genetic disease and their chance of having an affected child is 50%.

We recommend that families at-risk for inherited genetic diseases consult with their physician to determine if preimplantation genetic testing (PGT) of their embryos is a reproductive option.

PREIMPLANTATION GENETIC TESTING AVAILABLE AT CCRM

PGT for Aneuploidy (PGT-A)

CCRM was the first fertility center to offer PGT-A, also known as comprehensive chromosome screening (CCS), on a day five or day six embryo starting in 2007. CCS is a technique that counts all 23 pairs of chromosomes, performed in conjunction with IVF. During this procedure, embryos are cultured in the lab to the blastocyst stage (day 5 or 6 of embryonic development) prior to 3-6 cells being removed (biopsied) to test for chromosomal numeration.

PGT-A is recommended for women age 35 and older, whose eggs are at increased risk for chromosome errors, and for women with a history of multiple miscarriages or repeated implantation failure. CCRM PGT-A success rates are some of the highest in the nation, including a significant reduced risk of miscarriage (less than 5%) and increased live birth rates. Through CCRM’s efforts, more than 5,000 healthy babies have been born following the transfer of embryos with the correct number of chromosomes.

As pioneers of blastocyst CCS, the team at CCRM has implemented technology changes over the years allowing for developments in the laboratory to be tested and transferred into clinical practice. These have provided fantastic benefits to patients including faster turnaround time for results, a deeper look at embryonic chromosomes and added cost effectiveness.

PGT-A for Family Balancing/Sex Selection

For families wanting to choose the sex of their baby, CCRM offers PGT-A for the purpose of family balancing. By analyzing the sex chromosomes of an embryo during the IVF process, we can report male embryos with an X and Y chromosome, and female embryos with two X chromosomes.

Preimplantation Genetic Testing for Monogenic (Single Gene) Disorders (PGT-M)

PGT-M was first developed in the early 1990s to screen embryos for X-linked diseases, such as Fragile X. The technology has improved to include any inherited genetic disorder that has a known mutation such as cystic fibrosis, Tay-Sachs disease, muscular dystrophy, and more recently hereditary cancers, which have a 50% chance of being passed onto the embryo. (Learn more about Hereditary Cancer & Disease Prevention).

PGT-M tests biopsied embryonic cells for the specific genetic disorder that is inherited within the family. Embryos identified to be free of the single gene disease are selected for transfer to the uterus during an IVF cycle. Tens of thousands of unaffected children have been born worldwide from PGT-M for hundreds of different inherited single gene disorders.

Preimplantation Genetic Testing for Chromosomal Structural Rearrangements (PGT-SR)

What Are Translocations/Chromosomal Rearrangements?

In some instances, sections of chromosomes are rearranged and found in a different position than expected (known as chromosomal rearrangement). Individuals that have chromosomal rearrangements are healthy carriers, but have an increased risk of infertility, miscarriage, stillbirth, and/or having a child with a chromosome abnormality as a result of an unbalanced form of their rearrangement.

Two main types of chromosomal rearrangements include:

• Reciprocal Translocations: in which segments of two different chromosomes break off and change places
• Inversions: in which a segment of a chromosome has reversed orientation

What is PGT-SR for Translocations/Chromosome Rearrangements?

Preimplantation genetic testing for structural rearrangements (PGT-SR) for translocation/chromosome rearrangements helps to identify embryos that have the correct amount of chromosome material (balanced/normal) and embryos that have extra or missing chromosome material as a result of the translocation or rearrangement (unbalanced).

PGT-SR can reduce the likelihood of a failed implantation or an early miscarriage, or of having a child with a chromosome abnormality (which can lead to birth defects and intellectual disabilities) and increases the chances of a healthy pregnancy after an in vitro fertilization (IVF) cycle.

Origin of Aneuploidy

Aneuploidy is the presence of an abnormal number of chromosomes in an embryo which may result in arrested embryo development, failed implantation, miscarriage or chromosome abnormalities in newborns (including genetic birth defects and intellectual disabilities). Aneuploidy can originate from the sperm and/or the egg. CCRM Genetics can determine if the chromosomal error originates in the egg or sperm allowing your CCRM physician to customize your clinical management.

PGT and Genetics Research

CCRM Genetics is continuously finding new ways to improve patient outcomes. The following CCRM Genetics clinical studies are currently underway on PGT:

• Non-invasive comprehensive chromosome screening: this preimplantation technique analyzes nutrient-rich solution surrounding the embryo for the presence of DNA instead of invasively removing cells from the embryo itself. This has the potential to eliminate the invasive biopsy procedure from the PGT procedure.
• Investigating additional genetic tests as an adjunct to PGT in order to offer higher success and outcomes to IVF patients from the first frozen embryo transfer.