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When couples at risk of passing on an inherited single gene disorder like cystic fibrosis want to have a baby, they often consider in vitro fertilization (IVF) with preimplantation genetic testing (PGT). This form of testing can help prospective parents ensure that their children don’t inherit the gene mutation. Before undergoing the procedure, however, parents understandably want to know the likelihood of success of PGT. How probable is it that PGT will result in a healthy pregnancy and baby?

The answer to this question is not a simple one and is influenced by a wide variety of factors. The chances of success with PGT for single gene disorders (PGT-M) depends primarily on five factors. We’ll explore these success factors here to better understand what they are and what questions you might ask your doctor or IVF care team to better understand your chances of success.

1. Test Design

Part of the PGT process is designing a genetic test that can be used on the embryos after fertilization to determine whether they have a single gene disorder passed down from one or both of their parents. While it may seem simple to test for a single gene disorder, testing an embryo is very different from drawing blood from a baby — very little DNA can be taken from five to 10 biopsied cells.

“When we are designing a test for a single gene disorder, we’re never looking at just the disease mutation itself,” says Erin Armenti, MS, LCGC, a genetic counselor at CooperGenomics, a lab that performs PGT. “When possible, we examine the mutation directly, but we’re always looking at the normal DNA variants that surround that gene to give us the pattern of inheritance.”

That means DNA testing from not only the prospective parents, but also other family members, is critical to the test design. Knowing which family members carry the gene for the disease and which other genetic markers surround the affected one helps confirm the test results in the embryo.

“For instance, if we know the disease is inherited from the mother’s side, then we know that other neighboring genes from the mother will be associated with the disease mutation,” explains Armenti. Depending on the specific disease, there may be an increased chance of getting inconclusive results, according to Armenti. In this case, DNA testing of additional family members may become crucial to the test design.

Armenti says labs will often take into consideration all the specific, unique factors of each case before committing to designing the test, including how many DNA samples they have from which family members, as well as the unique genetic profile of the disease. “We very rarely tell patients that we absolutely can’t design a test for them, but if we don’t think we can, we will tell them that, and give them options going forward.” For example, if parents decide to try to conceive naturally, the DNA from a prior pregnancy or live-born child may allow a test to be built in the future.

Other options for prospective parents who can’t have a test built for them include using donor eggs or donor sperm to avoid passing on the genetic mutation.

2. Parental Age

The age of the parents will affect the success of PGT as well. For women who are beginning their PGT journey at an older age, there is an increased likelihood that aneuploidy, or random chromosomal errors, will occur in the egg cell. Older women also produce fewer eggs overall. Parents can choose to add an additional PGT procedure (known as PGT-A) to test for aneuploidy. While adding this additional test will decrease the chance of finding an embryo that “passes” both tests, the chromosomal makeup of an embryo is an important indicator of an embryo’s viability. Women over 43 years of age may want to consider an egg donor.

For older men, there is an increase in de novo mutations, or changes in genes that happen with that specific conception. From an assisted reproduction standpoint, there is no way to detect these mutations, says Armenti, so “our hands are tied. We have no way of knowing what they could be, so we can’t test for them.” It’s simply an increased risk factor for couples to be aware of and during pregnancy patients may choose to do additional ultrasounds to screen the anatomic health of the baby. Using donor sperm would be one possible way to avoid this risk.

3. Female Factors

IVF success factors specific to the potential mother, such as hormone levels, follicle count and uterine health, can also affect the success of PGT. Clinics use hormone levels to measure ovarian reserve and to understand how a woman might respond to IVF medications. Follicle count determines how many eggs she may have available.

Both follicle count and ovarian reserve can affect how many embryos are created during each IVF cycle and thus, the number of unaffected embryos that can potentially be transferred to the uterus. Uterine health, meanwhile, may impact the likelihood of a successful embryo transfer. Depending on these factors, an egg donor or gestational carrier (surrogate) may be a possibility for increasing chances of success.

4. Male Factors

There are also IVF success factors specific to men that couples seeking PGT need to consider. It’s possible that the male partner has a low sperm count or abnormal sperm test. There are many potential causes of male factor infertility, some environmental and some genetic. Depending on the cause and your fertility specialist’s advice, a sperm donor or testicular sperm extraction (TESE) may be options for achieving greater success with PGT.

5. Clinical IVF Success Rates

Finally, your clinic’s success rates with IVF with PGT will influence your individual success with the technology. Looking at the clinic’s SART data can help you choose the best clinic for you, but it’s important to look at those success rates based on the type of IVF cycle (such as with PGT) rather than just directly comparing clinic data. There are filters you can use to look at SART’s National Summary Report this way.

PGT is an excellent option for couples with inherited single gene disorders, but there are some factors that can influence its success rate. Before opting for IVF with PGT, talk to your doctor about the above five factors to determine how likely PGT will be successful for you.