Your IVF cycle appeared to go perfectly. You retrieved a number of eggs. Many of them were
mature eggs which fertilized and developed into expanded blastocysts. Because you were older,
you biopsied these blastocysts and had testing to determine the number of chromosomes. Then you
transferred one of these chromosomally normal blastocysts into your uterus,
waited eight days and then had a blood test to determine if pregnancy occurred.
You waited patiently for the results to come in and then were devastated to learn it was negative.
What went wrong? Why did the transfer of a PGT normal embryo not result in a pregnancy
or live birth? Part of the answer may be that the embryo was not actually normal at all.
Let me explain.
In 2022, IVF programs have two methods for evaluating an embryo. First,
we can see whether an embryo develops appropriately to the blastocyst stage.
Second, we can determine whether the embryo has the correct number of chromosomes.
Normal embryos have 23 pairs of chromosomes. These two techniques will help identify a number of
abnormalities that could cause an embryo to fail. Failure could mean the embryo does not implant
or implants and then miscarries or results in a baby with congenital abnormalities.
There is another type of abnormality present in embryos that we do not yet have an easy way
to test for - these are problems with the genes. These problems include mutations in a single gene
in which the structure of the gene has been changed. There are many diseases that occur
in live born humans which occur as the result of mutations in a single gene. With our current
technology, the only way to identify these mutations in an embryo is if you know ahead
of time that one or both of the parents is a carrier for the mutation or is known to already
have that disease. Watch this video about genetic carrier screening that potential parents can do.
If there are genetic mutations that cause diseases in live born people couldn't there
also be genetic mutations that cause an embryo to miscarry or fail to implant? The answer is yes.
Here are just a few examples. This 2019 study found that mutations in the gene
that makes a protein called folliculin would cause a blastocyst to fail to implant.
This study found that mutations in the MOS gene caused embryos to simply stop developing.
Various mutations in these genes have also resulted in embryos failing to divide at all
or by stopping their development at some point during the first several days after fertilization.
All of these examples were genetic mutations in the embryos that prevented implantation.
Genetic mutations can also block implantation of an otherwise normal embryo by affecting the
uterus. Followers of this channel might remember this video we did about mutations in the FOXD1
gene. People with these mutations are 10 times more likely to suffer from recurrent miscarrige.
This study has also identified some FOXD1 mutations as interfering with implantation.
There are a family of related genes that make up what is called the P53 pathway.
Scientists have found that some variations in the genes of the p53 pathway
are associated with a lower likelihood of embryo implantation
Please realize that the study of genetic mutations and IVF failure is just beginning. Human beings
have somewhere around 30,000 genes. In the year 2000, we only knew about 1000 genetic diseases.
By 2006, that number had increased to 2000. As of March 2022,
over 6000 separate conditions have been identified that are caused by over 4000 different genes.
It is likely that there are hundreds, maybe thousands of genes that have an
impact on embryo development, implantation or miscarriage. We hope that in the future,
we will have new technologies that will allow us to identify these abnormalities in an embryo or
person looking to carry a pregnancy. Until then, it is important for doctors to stop
saying things like “everything was perfect when it is likely that not everything was.