Preimplantation Genetic Diagnosis in Chicago

At Reproductive Medicine Institute, we strive to offer our referring community and our shared patients the most current information on Assisted Reproductive Technologies (ART). In this blog, we discuss preimplantation embryo genetic screening.

Preimplantation Embryo Genetic Testing

John S. Rinehart, MD, PhD

Preimplantation embryo genetic testing:

Medicine has benefitted tremendously from the digital revolution as applied to the field of molecular biology. The revolution permitted the field of molecule biology to move into mainstream clinical practice. One example of this is the ability to determine the chromosome number of embryos before they are transferred. So why is this such a big deal?

Genetic testing: the phrase “genetic testing” has been applied to a number of different settings. One type of testing is prenatal carrier screening, where a person can have their DNA tested for single gene errors. People can have a number of errors in their genetic code but if the male and female both have the same gene error then there is a one out of four chance that their offspring could have the genetic disease, many of which are devastating. Embryos can be tested to determine if the embryo will result in a person with the disease and the parents can choose not to transfer the affected embryo. The second type of embryo testing can be done if a genetic disease runs in a family. The embryo can be tested for the family’s mutated gene and again the embryo need not be transferred. The actual number of people who are faced with these types of a genetic diseases is small compared to the number of couples who undergo IVF and have embryos that have the wrong number of chromosomes.

Chromosomes and chromosome number: The genetic code is a language a cell uses to construct a person. The language has only four letters (ATCG) and uses words that are three letters long. An example of a genetic disease that results from errors in the words is fragile “X” syndrome. Fragile “X” syndrome is a genetic disease where the affected individual has too many copies of the sequence CGG. Unaffected people have 5-44 repeats of CGG. If there are 45-54 repeats it is considered a gray zone but 54- 200 is considered abnormal and a female with this problem can experience premature ovarian failure. For individuals over 200 repeats, the consequences can be severe in the form of lower IQ, infertility, autism, and social development.

The three letter words are used to make sentences that tell a cell how to make proteins. These sentences are called genes. The sentences are grouped together in paragraphs called chromosomes. Each paragraph is a chapter in the book, “Making a Human”, and each chapter has two copies: one from mom and one from dad. That means there are 23 sets of two chromosomes. The body contains trillions of cells so somehow a cell has to divide to make two cells and that means the chromosomes need to be duplicated and then separated equally so that each daughter cell gets the correct number of chromosomes. This is a complicated and inexact process, where the results of errors can be seen clinically in individuals born with three sets of chromosome 21, which is Down syndrome.

Embryos and chromosome number: The formation of human embryos is a very inexact process with the majority of human embryos having the wrong number of chromosomes. One might think that one egg would form one embryo with the correct number of chromosomes (euploid embryo). However, even when the eggs are as good as eggs get (young, oocyte donor eggs), up to 30% of the embryos may have the wrong number of chromosomes (aneuploid). Embryos can be tested to determine if they have the correct number of chromosomes and then only those with the correct number can be transferred. There is considerable variation amongst experts in the predicted pregnancy rate for each euploid embryo transferred but approximately 50% of the patients who have one euploid embryo transferred will have a child. Science is working to try to understand why the other 50% do not have a child, but that work is still in its infancy.

Preimplantation embryo testing for chromosome number (PGT-A): Technology has progressed to a point where embryos can be tested for chromosome number. There remains considerable controversy about how this should be used in clinical practice. One camp says it is unnecessary and another says every embryo should be tested. As with almost all clinical medicine, the utility lies somewhere between these two camps and needs to be tailored to the individual patient. Performing testing does not correct the chromosome error. That means that for a retrieval in IVF, the number of euploid embryos is set so doing the testing will not increase the pregnancy rate per retrieval. However, avoiding the transfer of aneuploid embryos does increase the pregnancy rate per transfer and lowers the miscarriage rate per transfer. The percent of embryos derived from a retrieval increases with age such that for women over the age of 41-42 as many as 90% of the embryos are aneuploid. Some women under 41 will have no normal embryos from a retrieval cycle. That can be true for some women in their mid and even early 30s. Some physicians have advocated the use or PGT-A for recurrent pregnancy loss patients but American Society for Reproductive Medicine (or ASRM) has taken the stance that this is not clinically indicated. However, a recent presentation at the annual ASRM meeting did suggest a role for PGT-A for patients with recurrent pregnancy loss (RPL). The utility of PGT-A lies in the information derived from testing the embryos and thus will vary person the person.

Limitations: The primary limitation is cost since PGT-A is usually not considered a covered benefit. Secondly, PGT-A is new and long-term, follow-up studies have not been done.

Conclusion: PGT-A can prove to be a powerful diagnostic tool in the correct clinical setting. Presently, widespread use of PGT-A is not indicated. Discussion between the patient and the physician can determine when PGT-A would provide valuable information and thus is worth the expense.

At RMI, our goal is for the patient to have a healthy, successful pregnancy. We understand that each patient experiences their own unique journey through fertility. Our team is here to provide your patients with the information needed to meet their needs while giving them the best chances of having a successful pregnancy and a healthy baby.