If you're planning to undergo in vitro fertilization (IVF), you may have heard the term preimplantation genetic screening. Preimplantation genetic screening (PGS), also known as aneuploidy testing, is a genetic test carried out on IVF embryos before transfer. It's an option available to individuals or couples undergoing IVF, and it involves genetically testing the embryos before embryo transfer. These tests can be done:
- To reduce miscarriage rates by transferring only genetically normal embryos
- To eradicate a genetic disorder from a family
- For the purposed of gender selection (although this is somewhat controversial)
- For patients who have a poor prognosis with IVF
If you're curious about or are considering PGS, it can help to understand how this testing is carried out and whether you are likely to benefit. Here we'll take a look at PGS in depth.
What are chromosomes and why do they matter?
To understand the genetic testing of embryos, you must first grasp some basic cell biology. Each cell in the body has 46 chromosomes, except eggs and sperm, which each have 23. The egg and sperm combine to give the offspring a total of 46 chromosomes. We inherit half of our chromosomes from our father and half from our mother. These chromosomes act like instruction books and control the function of our cells.
If an egg or a sperm is missing a chromosome, then the embryo created from that egg will also be missing a chromosome and a whole set of instructions. If there is an extra chromosome in an egg, the embryo will be abnormal, having twice as many copies of those instructions then it should have. Down Syndrome is one example of a genetic disorder that can be caused by an additional copy of a chromosome.
Most such embryos will not implant at all, some will cause an early miscarriage and some can go to full term and be born. Almost all of the babies born with extra or missing chromosomes will have some kind of physical and/or mental disability.
Why undergo preimplantation genetic screening?
In most studies, preimplantation genetic screening has not been shown to improve pregnancy rates for the general population undergoing IVF. However, it has been shown to:
- Reduce the miscarriage rate for women with a history of recurrent miscarriage
- Be beneficial for women of advanced maternal age (leaning more heavily towards 37 and over)
- Be beneficial for individuals or couples who have had repeated failed IVF cycles
Genetic Counseling as Part of the PGS Process
If you are considering testing your embryos during an IVF cycle, you will likely be referred to a genetic counselor who will ask extensive questions about your family history. This counselor will also take into account the age of the female partner and tell you your chances of having normal embryos during your IVF cycle.
A genetic counselor, as well as your doctor, should discuss the pros and cons of testing your embryos as per your specific situation and whether it’s the right decision for you.
How Embryos Are Tested During Preimplantation Genetic Screening
It’s possible to test each individual embryo created by IVF and count the number of chromosomes. This is done by taking cells called blastomeres from the embryo on day three, day five, or day six of development and running a test on those cells to determine the embryo’s genetic makeup.
Embryo testing can be performed on either day three at what's called the morula stage, or around day five at the blastocyst stage. The advantage of doing a blastocyst biopsy is that several cells can be tested, thereby reducing the risk of a false result.
However, if embryos are tested on day five or day six at the blastocyst stage, they usually have to be frozen because the results aren’t available in time for a fresh transfer. A few clinics do offer overnight testing and this option may become more available with time and better technology.
Some clinics offer to test the “spare” embryos from an IVF cycle. In this case, you get a fresh transfer of untested embryos and any extra embryos of suitable quality will be biopsied before being frozen.
PGS and Embryo Growth
The removal of cells from the embryo at these early stages does not affect an embryo's development in terms of making it abnormal. The embryo can usually compensate for the damage within a few cell divisions. In good hands, the biopsy of an embryo has little effect on its growth, although it may slow down slightly.
That said, the biopsy itself is very invasive, and there is a chance that a normal embryo that would have otherwise implanted could be damaged beyond repair. This is a major risk in PGS: it can compromise the viability for the embryo tested. Note that this will not lead to abnormalities in a baby. In this case, the embryo has been damaged so that it is no longer able to implant.
Cost Is a Major Consideration for PGS
Another thing to consider with PGS is that it incurs additional fees on top of those charged for your regular IVF cycle. In general, the cost of PGS includes three fees:
- Biopsies charged by your IVF clinic
- Shipping of biopsies charged by your IVF clinic
- Testing charged by the genetic testing lab
All these charges are refundable if there are no embryos to biopsy. The total cost for embryo testing is in the region of $5,000, not including the cost of frozen embryo transfer cycles that will be incurred to transfer the tested embryos. This can also be several thousand dollars.
Remember that so far data have shown that women over 37 are most likely to benefit from embryo testing, whereas younger women may have better success without it.
The Limitations of PGS Genetic Testing
PGS does have some limitations. The rationale behind the test is the presumption that each cell in the embryo is genetically identical. In other words, if you test one cell from the embryo, you know what all the other cells are. However, there have been reports of embryos exhibiting mosaicism, where not all the cells are identical. This leaves open the possibility of misdiagnosis and the discarding of normal embryos or the transfer of abnormal embryos.
Because most genetically abnormal embryos stop growing before the blastocyst stage or fail to implant, most women do not have increased pregnancy rates following PGS. The outcome of the IVF cycle is likely to be the same with or without the testing. The main difference is that by doing PGS, you have the information sooner rather than later. PGS can help women struggling to decide whether to continue to use their own eggs after several failed IVF cycles.
The Potential Pros of Seeking Preimplantation Genetic Screening
- It allows lab personnel to identify normal embryos for transfer for women of advanced maternal age or with repeated implantation failure or miscarriage. This will lead to a FASTER time to pregnancy for women in this group.
- It saves time and money by avoiding the transfer of embryos that are genetically abnormal in frozen embryo cycles
- It reduces miscarriage rates
- It provides information to help you make decisions about future treatments
- It can help avoid the need for invasive testing once pregnant
- It can provide peace of mind
Potential Cons of Seeking Preimplantation Genetic Screening
- There is usually no improvement in pregnancy rates for younger women with a good chance of success. In young, healthy women, testing may actually decrease the chances of success because the embryos have to go through an invasive biopsy and freezing process, both of which can damage them to some degree.
- Normal embryos could be damaged during the biopsy. The biopsy itself is very invasive, and there is a chance that a normal embryo that would have otherwise implanted could be damaged beyond repair.
- Normal embryos could be damaged during freezing. At this time, all PGS embryos must be frozen until the results from the genetic testing have been processed. This additional step of freezing and thawing the embryo can further compromise its potential for pregnancy.
- Results may not be 100% reliable
- The cost could be prohibitive for some couples
- You must pay for a subsequent frozen embryo transfer cycle if you choose to freeze all your embryos
- Theoretically, it does not eliminate the need for prenatal testing
How are embryos chosen for transfer following PGS?
If you decide to undergo PGS, the embryos chosen for transfer have to be:
- Genetically normal
- Have a normal pattern of growth
- Survive the freeze-thaw process
There is no point transferring a four-celled embryo on day five that has clearly stopped growing, even if the genetic analysis comes back normal. In other words, there is always a chance of not having an embryo transfer regardless of the PGS results.
Preimplantation Genetic Screening and Maternal Age
Because PGS is not without risk to the embryo, it is important to consider who is most likely to benefit from the procedure. Data collected so far have shown that the risks outweigh the benefits for younger women (the pregnancy rates are lower with testing). But for women aged 37+, the benefits outweigh the risks, and we are seeing improved pregnancy rates for this group.
Your Options for Genetic Testing of Your Embryos During an IVF Cycle
In this case, both the embryos transferred in the fresh cycle and subsequent frozen embryo replacement cycles have unknown chromosomes. You then have the option to do genetic testing on the baby after a pregnancy is established, while it’s growing in the womb. This is the best option for young women who have a good chance of success.
Test Spare Embryos Only
In this case, the embryos transferred in the fresh cycle have unknown chromosomes. Any subsequent frozen embryos transferred are tested. This saves time and money transferring embryos that are chromosomally abnormal and should improve the pregnancy rate for the frozen embryos transferred. This option is best if you want good information about your spare embryos, have a good chance of success without genetic testing with your fresh embryos, are interested in reducing the chance of a pregnancy/child with an abnormality in chromosome number, or are interested in knowing the gender in future cycles.
Test All Embryos
Testing of all embryos is generally recommended if you want as much information as possible before transfer, are interested in reducing the chance of a pregnancy/child with an abnormality in chromosome number, would not do any testing on the baby after a pregnancy is established, are of advanced reproductive age, have had two or more miscarriages, have gone through multiple failed IVF cycles, have a previous pregnancy or child with an abnormality in chromosome number, or must freeze all of your embryos anyhow.
Some IVF cycles produce only one or two embryos of suitable quality for testing. In this case, you can choose to freeze the embryos and undergo another IVF cycle in the hope of having additional embryos to test. This is called embryo banking. It’s a cost-effective way to test embryos from several IVF cycles; you pay the testing fee only once. The embryos can be frozen before or after biopsy, depending on your clinic’s procedures.
PGS and a 'No Diagnosis' or 'Mosaic' Result
Sometimes embryos that undergo PGS have a “no diagnosis” result. This means that the test failed for a particular embryo. Some couples choose to transfer these embryos anyway, despite not obtaining any information about that particular embryo.
Sometimes embryos that undergo PGS have a "mosaic" result. This means there was a mixture of normal and abnormal cells. Most clinics do not allow the transfer of mosaic embryos a this time.
PGS and Karyotyping
PGS can also be used to detect translocations in the embryos, which are changes in the structure of the chromosomes. Changes are quite rare but do account for some cases of recurrent miscarriage or implantation failure. It’s estimated that 1 in 700 people carry a translocation.
If you have suffered multiple miscarriages or multiple failed IVF cycles, it might be a good idea to talk to your doctor about checking the structure of the chromosomes for translocations in the female and the male partners. This testing is called karyotyping.
Testing for Recessive Genetic Disorders
At any stage, you may be offered to test for recessive genetic disorders. These are diseases that lie dormant in DNA and could be passed onto a child if both partners carry the same recessive genes. If you want to learn more about this type of testing, ask your doctor.
Preimplantation Genetic Screening (PGS) Versus Preimplantation Genetic Diagnosis (PGD)
PGS counts the overall number of chromosomes, but preimplantation genetic diagnosis (PGD) identifies a specific disease in a preimplantation embryo.
Genetic diseases are often caused when a gene mutates or the instructions have become misspelled on part of the DNA. This causes the cell to malfunction and not produce the correct proteins needed to do a specific task in the body. Genetic diseases of this type are called single-gene disorders.
A person who carries this type of genetic disorder can undergo a cycle of IVF. This presents an opportunity to eliminate this disease from the family and future generations. The accuracy of the results is close to 100%.
Although PGD carries some risk of damaging the embryo during biopsy, for some this risk is offset by the peace of mind in knowing a child will not inherit a potentially debilitating or even lethal disease.
PGD is able to detect the following diseases and many more:
- Cystic fibrosis
- Sickle cell anemia
- Tay-Sachs disease
- Myotonic dystrophy
- Muscular dystrophy
- Fragile X syndrome
- Spinal muscular atrophy
- Huntington’s disease
In PGD testing, cells are removed from each embryo during early development and the DNA is multiplied many times. A specially made probe is then used in the specific region of DNA (or gene) that carries the disease mutation. The results confirm whether each embryo is carrying the defective gene or has normal genetics.
Choosing the Gender of Your Baby with PGS
Preimplantation genetic testing can be used to detect the gender of the embryos when a baby of a certain sex is desired. Even though this is a controversial use of reproductive technology, most clinics offer this as a service. Some clinics have restrictions on which families they allow to choose gender. They may require a couple to already have children and want a child of the opposite sex. This is called family balancing.
During an IVF cycle, the embryos are biopsied and analyzed the same way as in PGS testing. The other chromosomes are also tested at the same time to ensure genetic normalcy of the embryo, as well as gender.
At the time of the embryo transfer, you are told the results of the genetic analysis and the quality of the embryos. It’s possible that there may not be good-quality embryos of the desired gender. In this case, you would have to decide whether to transfer the alternate gender or lower quality embryos.
Should you Choose PGS?
This is a very personal question that each couple must weigh based on information from their fertility treatment team. PGS has been shown to have benefits for women of advanced maternal age. It can also reduce miscarriage rates and provide peace of mind. The downside of doing PGS is that there is a potential of disrupting the embryo growth by doing the biopsy. The procedure is also very costly and may not provide an accurate result.