Preimplantation Genetic Testing

Individuals who carry genetic mutations such as BRCA, CHEK2, PALB2, ATM, Lynch Syndrome, etc. that could be passed on to their children, thereby elevating their children’s risk of a hereditary cancer diagnosis, and carriers of other mutations associated with genetic conditions, such as Huntington’s Disease or Marfan’s Syndrome.

Couples who are both mutation carriers for the same recessive genetic condition, such as cystic fibrosis or Tay-Sachs disease, and individuals who have a personal or family history of a genetic disease, including a pregnancy or child with a genetic or chromosome condition, would also be considered candidates for PGT.

If you are considering pursuing PGT-M, we encourage you to speak with a fertility or reproductive specialist who will provide more information and guidance.

PGT-M is a tool available to help build families but is not required.  It is important to remember:

• IVF and PGT-M do not have 100% success rates.
• Any mutations that are present in a parent – the ones you know about and the ones you don’t know about – can be passed along at a 50% rate.
• Having a child naturally does not mean that s/he will automatically be a carrier of any genetic mutations that the parents may carry.
• Couples should be aligned about whether they intend to pursue PGT and also about what to do if first attempts do not result in a successful pregnancy.

PGT-M can be a very controversial subject, and sometimes partners or their family members don’t agree on it.
PGT-M can be cost-prohibitive even if there were couples who ideally would like to pursue it.
No matter the reason, whether to pursue PGT-M is a very personal decision that should be made thoughtfully and carefully.

Each child of a BRCA mutation carrier has a 50% chance of inheriting the mutation. Most hereditary cancer syndromes do not pose risks to children to develop cancer as children, meaning that they can be raised “normally.”  A parent may choose to share information about healthy lifestyles, family history, and cancer risks in developmentally appropriate ways.  Genetic testing is not recommended until the child is at least 18 years of age.

All types of PGT (M, A, and SR) are completed in the same manner using IVF. After the egg retrieval, the sperm and egg will be combined to form an embryo. Around day 5, the embryo is a mass of cells that resembles a ball composed of two parts: an outer layer and an inner layer. At this point, an embryo biopsy is performed, during which a couple of cells are removed from the outer layer of the embryo; these are the cells which will eventually develop into pregnancy structures, like the placenta and membranes.  It is thought to be safer to remove cells from the outer layer since pulling cells from the inner layer (which will become the fetus) might be damaging to normal development. The cells of the outer layer are generally expected to be representative of the entire embryo.

The embryo will stay in your reproductive center while the biopsy is sent to the laboratory of your choice for further testing. The laboratory will design a custom test for the embryos, called a probe, based on your personal and family medical history. This may require meeting with a reproductive specialist, genetic counselor, or laboratory technician; additional documentation or blood/saliva samples may be needed to design the probe.

The number of cells being tested is much smaller with PGT-M than when you have genetic testing done on a vial of blood or saliva. The embryo biopsy is microscopic and made up of a very small number of cells, probably less than a dozen.  In order to test such a small number of cells, a special probe must be made just for you, which will test for the mutation that has already been identified in one or both parents.  This also allows for the highest accuracy possible; if the PGT-M test does not detect the mutation, you can be highly confident that it isn’t there.  Blood/saliva samples will be needed from the parents of the embryo and sometimes from other family members as well. The probe can take a few months to complete.

The cells that are evaluated by the probe are destroyed in the process of testing. The biopsied cells can never be returned to the embryo.  If the egg or sperm were tested, they would not be able to be used.  Also, the egg and sperm each have only half the DNA (23 chromosomes) of a typical cell; the full amount is present after the egg and sperm merge (46 chromosomes).

A woman’s fertility begins to decrease with age and probably peaks before 30 years of age.  If you know you will want to use IVF, you may want to consider retrieving eggs at a younger age and freezing them.  In terms of quality, freezing eggs keeps them at the age they were when they were retrieved.  You may be older when you are ready to have children, but the quality of your eggs will be related to the time when they were harvested, not the time when they were thawed.

Freezing eggs requires a lab that has experience with freezing and thawing eggs.  When you freeze your eggs, there are no concerns about “custody,” which can arise when a couple who freeze embryos ends their relationship.

Women who are BRCA-mutation carriers may have a reduced ovarian reserve (fewer number of eggs responding to hormones), or they may undergo menopause at an earlier than average age.  This might be more likely with BRCA1 than BRCA2, although the studies are not conclusive.

Once the pregnancy is well established, you will switch from the fertility practice to a “regular” obstetrician.  This is generally between 8 and 12 weeks of pregnancy. This can feel like a big adjustment, since you will no longer have as many visits with the doctor. Your pregnancy will likely be treated as high risk, even if there is no indication that you are at high risk other than your having pursued PGT.

Some of the challenges cited most frequently include the following:

• As part of the IVF process, hormones are given to stimulate the development of egg follicles before the retrieval, and again after the implantation of the embryo. Often, these hormones are given by injection, which can be painful.  Also, some women report that taking hormones can make them feel like they are on an emotional roller coaster.
• IVF and PGT-M are processes that require significant time and funds, and they involve many physician appointments.

Pursuing IVF and PGT-M can strain a couple’s relationship. Some choose to explore mental health counseling, while others seek confidantes such as peer supporters with whom to discuss some of their experiences.

It’s important to have realistic expectations when having a child using IVF and PGT-M. This process does not prevent all birth defects, unknown genetic mutations, or health problems in your children. There is always a 3-5% risk that a child will be born with another health condition or birth defect (e.g., autism) that cannot be predicted prior to birth. Also, if you haven’t yet tried to have children naturally, you won’t know if you have fertility issues that are yet to be discovered.

Because of their fragile state, some embryos do not survive to the biopsy stage or the thawing process (if they were frozen) prior to being transferred. Also, for reasons we can’t always explain, some embryos stop growing and cannot be used for transfer.

It is possible that some or all of the embryos that are biopsied will be found to have a genetic condition; in fact, there can be a big drop-off from the number of eggs retrieved to the number of embryos that are found to be genetically healthy and developing normally. Multiple cycles may be required to yield the desired number of embryos, and it may be best to overestimate the number of eggs that are needed.

The cost of PGT varies depending on various factors, including insurance coverage, personal and family medical history, and laboratory costs.  IVF, which is a necessary component of the PGT process, can cost between $25,000-50,000 without grants or insurance.

Pursuing IVF and PGT-M does not guarantee that a healthy child will be born; in fact, it may require multiple cycles to have enough healthy embryos to attain a healthy pregnancy.  Miscarriages may occur, usually for unexplained reasons.

In efforts to make PGT more affordable, women with insurance coverage often choose to complete as many costly procedures as possible during one insurance calendar year – these procedures could include egg retrievals, IVF, and (bilateral) mastectomy and reconstruction – in order to maximize benefits.  Also, select fertility clinics have unused, donated medications, and some communities advertise informal networks of women who share their unused and leftover medications.

Sharsheret has information about organizations that offer grants to individuals pursuing PGT, many of which are local to specific states or metropolitan areas.  It is probably helpful to search fertility resources in your local area – please let us know if you find any that we could include in our information bank.

To learn more about PGT, including personalized medical, technical, and financial considerations, please reach out to a reproductive specialist or medical provider near you.

Sharsheret can often find a peer supporter who is willing to discuss their own experience with you.  Please reach out to Sharsheret for more information.

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