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Jill Pinarowicz’s life has been shaped by a mutation in her mother’s DNA. The genetic error gave her two brothers a rare disease called Wiskott-Aldrich syndrome, which occurs in fewer than one in 100,000 births and almost exclusively affects males. Boys with the disorder are born without functioning white blood cells — a type of immune cell — which makes the body more susceptible to infections and causes spontaneous bleeding that can be life threatening. Within the first few months of life, babies with the disorder can develop eczema, severe nosebleeds, bloody diarrhea, and recurrent bacterial infections.
Both of Pinarowicz’s brothers passed away from complications of the disease. One died as a toddler, before she was born, and her other brother died at age 18, when Pinarowicz was a teenager.
“My whole childhood was completely traumatizing and chaotic,” she says. Her older brother’s life was punctuated by health emergencies. “He would end up in the hospital in the middle of the night, and we wouldn’t know if he was going to live or die.”
Wiskott-Aldrich syndrome is caused by a mutation in the WAS gene on the X chromosome. Because women have two X chromosomes, they can have a mutation in one copy of the gene and not have the disease — what’s known as a carrier. Even though she didn’t have the disease herself, Pinarowicz worried that she could pass on the mutation to her future children. So, when she was 23, she got tested to see if she was a carrier. The results came back positive.
Pinarowicz thought it would be too risky to have her own children. As a carrier of an X-linked recessive condition, the chance of having a boy with Wiskott-Aldrich is 50 percent. But years later, after meeting her husband, Pinarowicz learned about a powerful technology that would allow her to have children while being certain that she would not pass on the mutation that had killed her brothers and plagued her family.
The technique is called preimplantation genetic testing (PGT). By using PGT together with in-vitro fertilization, Pinarowicz and her husband had a healthy son in May 2017.
“I wanted to end my disorder completely. That was my plan when I started.”
PGT is a method of scanning embryos outside the womb to identify genetic abnormalities. After eggs and sperm are fertilized outside the body in the beginning stages of IVF, a thin needle is used to extract just a few cells from the resulting embryos. Those cells are tested for select genetic conditions, like Wiskott-Aldrich syndrome in the case of Pinarowicz and her husband. Parents can then choose which embryos they want to use, and the rest of the IVF process proceeds as usual. (The other embryos are frozen, discarded, or donated for medical research.) The technology gives families the ability to root out deadly genetic diseases like Huntington’s, cystic fibrosis, or Wiskott-Aldrich syndrome from their family tree.
PGT was first carried out successfully in 1990, and while it still isn’t widespread, it has become increasingly common. The U.S. Centers for Disease Control and Prevention (CDC) reported in January that PGT was used in 22 percent of IVF cases in 2016, up from just 5 percent in the previous year. As American couples wait longer to have children, more will likely need the help of IVF to get pregnant. The CDC reported that in 2016, for the first time, there were more women ages 30 to 34 having babies than women ages 25 to 29. Add to that a booming interest in personal genetics and an increasing number of employers willing to cover workers’ fertility treatments, and PGT is set to take off.
Widespread use of PGT represents a new era of family planning. Scientists are working to perfect and improve the technology, and in the future, such tests will be faster and more affordable. They could even enable parents to test for more common conditions like diabetes and even autism. Future advances might even permit parents to choose embryos with certain physical characteristics like height and hair color. As the technology advances, it will raise questions about who has access to a new way to have children — and how our society will change as a result.
Though PGT has been around for nearly 30 years, it’s mostly been used to identify aneuploidy, the presence of an abnormal number of chromosomes. The most common and well-known type of aneuploidy is Down syndrome. As a woman ages, her eggs — and thus, embryos — have an increased chance of aneuploidy, which is also a cause of spontaneous miscarriage.
What’s less common is testing embryos for single gene disorders, like the one Pinarowicz carries. Right now, only a small percentage of PGT is used to test for these conditions. One reason is that these conditions are fairly rare. Another is that would-be parents may not know PGT is available to screen for such conditions — something experts say could change very soon.
“I think the whole medical field is going to have to adapt to this concept that we have this other option that’s not focused on managing disease but preventing it in the first place,” says Zev Williams, chief of reproductive endocrinology and infertility at Columbia University Medical Center.
One major reason for a push for more PGT use from geneticists and reproductive specialists is that the technology could also save the health care system — not to mention families — tremendous medical costs that come with treating rare and serious genetic diseases.
“Having an opportunity to do something that would extend the life of your child is something many people are interested in.”
Consider sickle cell disease, a painful genetic blood disorder. A 2009 study found that the lifetime health care costs for a 45-year-old with sickle cell came to more than $950,000. Other genetic conditions — like cystic fibrosis, a frequently fatal disease that damages the lungs’ airways — can cost hundreds of thousands of dollars to manage in a single year. A drug approved for a subset of patients, called Orkambi and made by Vertex Pharmaceuticals, costs $272,000 for a year’s prescription.
There are treatments for such diseases in the pipeline that directly target faulty genes after children have been born. Such gene therapies are a one-time intervention designed to halt, reverse, or potentially even cure disease, but they come with sky-high price tags. One such therapy being developed by Novartis for infants and young children with spinal muscular atrophy — a muscle-wasting disease that’s estimated to afflict as many as 10,000 to 25,000 children and adults in the United States — could cost $4 million to $5 million for a one-time treatment, according to recent estimates.
By comparison, an IVF cycle in the United States runs about $12,000 to $15,000 before medications. PGT adds another few thousand dollars. That can bring the cost to $20,000 for a single round of IVF plus PGT, though many women need two or three rounds to get pregnant. It adds up, but as Williams notes, “When you compare it to the cost of a lifelong treatment for a child who has a disease, it’s minuscule.”
But not every prospective parent has access to IVF and PGT. In the United States, where the health care system is fragmented, it’s been hard to convince insurance companies to pay for IVF, says David Sable, a reproductive endocrinologist and early pioneer of PGT who is now an investor in the field. “The insurance company taking care of the mother today is not necessarily the insurance company that will be saddled with all the costs of taking care of the adolescent or adult years later,” he says.
Some states mandate that insurers provide coverage for IVF, but in most cases, couples have to provide proof of infertility. However, a small but growing number of companies — including Intel, Starbucks, Spotify, and Bank of America — provide fertility treatment coverage to employees. Some also pick up the cost of freezing eggs. “That’s just a pure business decision,” Sable says. “It’s an extremely effective way to recruit and retain employees.”
Most insurance companies will not cover IVF and PGT for an otherwise healthy woman who, like Pinarowicz, carries a potentially inheritable genetic disease. Pinarowicz and her husband have had five different insurance plans over the past few years — including policies from Aetna, Blue Cross Blue Shield, and Cigna — and all of them have declined coverage for IVF and PGT. Whether insurers will decide to cover the procedure specifically as a means to prevent a genetic disease in a future baby is unknown.
In addition to the possibility that IVF coverage will expand, improvements to embryo testing technology could also help bring down the cost and speed up the turnaround time for testing, which could increase the use of PGT. Currently, PGT involves a biopsy, in which a tiny needle is used to remove three to six cells from an embryo. The cells are then sent to a lab for analysis. That process is done by hand. Sometimes the biopsy can damage embryos, making them unsuitable for transplant to a would-be mother.
In the meantime, embryos need to be frozen, because it typically takes a few weeks to get the test results back. Freezing embryos is expensive, and not all embryos will survive the freezing and thawing process. Though there’s considerable debate on whether fresh or frozen embryos are preferable, some evidence shows that for women who produce fewer eggs, transferring fresh embryos leads to better pregnancy and birth rates compared to those who receive frozen embryos.
Williams thinks PGT could be enhanced by testing embryos on-site instead of sending them away for testing. His team at Columbia recently published a study that used handheld genetic sequencers about the size of an iPhone to rapidly identify genetic abnormalities in embryos. They sequenced a total of nine samples and found that one sample could be analyzed within 20 minutes, and five could be done within two hours. “With this procedure, the embryo can be tested and transferred right away,” Williams says. It’s also cheaper to do testing this way, which should lower the bar to insurers.
Fertility researchers are also exploring ways to test embryos without employing a biopsy. The Colorado Center for Reproductive Medicine (CCRM), one of the largest fertility clinics in the United States, has begun a clinical trial for an approach that analyzes the tiny amount of DNA released from embryos in a lab dish, instead of the cells from the embryo itself — no biopsy required.
Mandy Katz-Jaffe, scientific director at CCRM, says this method could be less expensive than current testing, and that it could improve the chance of a patient getting pregnant since fewer embryos would be destroyed along the way. Her clinic will be using the technology first to screen for aneuploidy; if it works as well as traditional embryo testing, they’ll expand it to single-gene disorders.
“With anything in medicine, there’s always a risk when you do an invasive test,” Katz-Jaffe says. “If we could get the same result but not do a biopsy, that would be a preferable option.”
Pinarowicz, now 41, is hoping to have another child with IVF. She wants a girl this time. When she began IVF to have her first child, she underwent three egg retrievals so she would have a few backups, just in case. Sometimes eggs don’t fertilize in the lab or embryos don’t attach to the wall of the uterus when transferred. But the female embryos she and her husband have left all have one mutation for Wiskott-Aldrich syndrome, making them carriers of the disease — like her. She just finished her fifth embryo transfer and is optimistic it will work.
“I wanted to end my disorder completely. That was my plan when I started,” she says. Now, if the latest embryo transfer results in a successful pregnancy, the Wiskott-Aldrich mutation will continue in her family line. A daughter almost certainly wouldn’t develop the disorder, but she might pass it on to her own children in the future. “That’s something I have to make peace with.”
In the near future, however, patients like Pinarowicz might not have to face that dilemma. Paula Amato, a reproductive endocrinologist at Oregon Health and Science University, says the gene-editing tool CRISPR could be used alongside PGT to correct embryos that harbor genetic mutations.
“If it turns out to be safe, why wouldn’t we use it?” Amato says of CRISPR. “You could increase the number of available embryos, increase the efficiency of the whole process, and decrease the number of embryos you have to discard.”
But the very success of such a process would create a host of thorny new ethical problems around reproduction. The same technology that could be used to edit out disease-causing genes in embryos could one day be used to create so-called designer babies, especially as embryo testing grows to include polygenic conditions — those where more than one gene is involved in the disorder.
“What could be more profound than letting a part of the population opt out of many forms of genetic disease?”
Genetic testing for polygenic diseases currently is neither reliable nor effective. It’s an emerging type of testing that uses complex algorithms to analyze multiple genetic variants and predict someone’s likelihood — known as a risk score — of developing a certain disease.
A few companies are already developing polygenic testing for embryos. One firm, Genomic Prediction, is offering parents a test to screen embryos for more common diseases like Type 1 and 2 diabetes, cardiovascular diseases, and prostate and breast cancer. This type of embryo testing, however, can only tell you the risk that your child will have one of these conditions; it can’t offer a clear yes-or-no answer like PGT for single-gene diseases.
Nathan Treff, chief scientific officer at Genomic Prediction, believes these expanded tests present an opportunity for parents to plan for their future children. “It gets to what people refer to as reproductive liberty,” he says. “Having an opportunity to do something that would extend the life of your child is something many people are interested in.”
Polygenic tests represent a major advance in what’s possible with embryo screening, but it’s important to remember that the tests are inherently uncertain — for now, at least — which may add even more stress to the usual anxieties of having a child. They also open the door to testing for traits that aren’t diseases, but rather for characteristics that have little to no impact on health but might be seen as socially desirable, like height, certain hair or eye color, and even intelligence.
Genomic Prediction says it can test the likelihood that embryos have intellectual disabilities, but out of ethical concerns, it won’t offer testing for high IQ. The company also doesn’t offer testing for what Treff calls “purely cosmetic” traits. “I don’t think designer babies are a major concern,” he adds. “This is something that could allow us to eventually reduce the prevalence of common diseases like diabetes and cancer. Many more people are interested in that than are interested in what color eyes their babies are going to have.”
Laura Hercher, a genetic counselor and professor of human genetics at Sarah Lawrence College, says PGT effectively already permits the creation of designer babies, because it gives parents an unprecedented degree of control over their future child’s genes. Eliminating genetic disease isn’t a bad thing on its own, but only some people will have the luxury of doing it, since costs put IVF and PGT out of reach for the vast majority. Hercher says we should be less worried about the possibility of designer babies than of the health disparities that could arise as a result of this divide.
“Out-of-pocket expenses alone put IVF out of reach to most families in the U.S.,” Hercher says. “For the bulk of people, this is not obtainable technology.”
Hercher worries that if coverage for IVF and PGT isn’t greatly expanded, genetic diseases will increasingly become the burden of the poor, something we’ve already seen with some noncommunicable diseases, like Type 2 diabetes. When diseases are more common in certain groups of people — like HIV/AIDS in the LGBTQ community and hepatitis C among drug users — they tend to become socially stigmatized. Hercher says she’s more concerned about this scenario than the possibility of parents choosing embryos for what she terms “trivial” characteristics like hair color and eye color.
In Iceland, for instance, the widespread availability of prenatal genetic testing has meant that nearly 100 percent of women choose to abort a fetus with Down syndrome, which has led to a near eradication of babies being born with the condition. Hearing-impaired people fear that cochlear implants and coming gene therapies could wipe out the deaf community. “What could be more profound than letting a part of the population opt out of many forms of genetic disease?” Hercher asks.
As we’re increasingly able to test more accurately for a greater variety of traits in embryos, parents will need to decide what characteristics they want to bestow on their future children. What was once left to chance will become an active choice — and therefore a responsibility.
Pinarowicz says that she’s felt guilty at times about choosing to go through with her last embryo transfer. She wonders whether she be should be bringing another person into the world who will be a carrier of the disease. “Most parents don’t know that they’re making this choice,” she says.
That’s what PGT provides — an informed choice. But with more available options to design our children’s genes, parents will be faced with decisions that previous generations never had to consider. That has major ramifications for future families and for society as a whole.