A baby with a disease gene or no baby at all: Genetic testing of embryos creates an ethical morass

In almost every way, the 2-year-old is the child that his moms dreamed of. He loves playing with cars and trucks. He delights in entertaining others. And he’s strong-willed: He knows what he likes and what he wants.

But there, in a gene tucked away on one of his chromosomes, an anomaly lurks.

The boy carries a mutation in the BRCA1 gene that raises his risk of developing breast, prostate, and pancreatic cancer. His moms knew about it when he was just a frozen embryo. But faced with a choice between transferring the embryo into her womb or not having a biological child, Samantha, along with her spouse, Jessie, chose the former.

“There’s a part of me that feels selfish, indulgent, self-conscious, like I shouldn’t have wanted this so badly or I shouldn’t have gone to such lengths,” said Samantha, who has the BRCA mutation herself and provided the egg for the pregnancy. (STAT is using pseudonyms for the women to keep private their son’s medical information.)

“I wish that I hadn’t passed it on,” she added.

Jessie and Samantha’s story speaks to an emerging ethical morass in the field of reproductive medicine: what to do when patients seeking to get pregnant select embryos with DNA that could lead to a disease or disability. Should clinicians’ desire to help their patients have children override concerns about possibly doing harm to those children? And what about cases in which patients — like Samantha and Jessie — end up with only one viable embryo through in vitro fertilization?

As Dr. Sigal Klipstein, a reproductive endocrinologist at InVia Fertility in the Chicago area, put it: “Would I rather have this baby with this disorder or no baby at all?”

The issue also pokes at a broader puzzle ethicists and experts are trying to reckon with as genetic testing moves out of the lab and further into the hands of consumers. People have access to more information about their own genes — or, in this case, about the genes of their potential offspring — than ever before. But having that information doesn’t necessarily mean it can be used to inform real-life decisions.

A test can tell prospective parents that their embryo has an abnormal number of chromosomes in its cells, for example, but it cannot tell them what kind of developmental delays their child might have, or whether transferring that embryo into a womb will lead to a pregnancy at all. Families and physicians are gazing into five-day-old cells like crystal balls, seeking enlightenment about what might happen over a lifetime. Plus, the tests can be wrong.

“This is a problem that the rapidly developing field of genetics is facing every day and it’s no different with embryos than it is when someone is searching Ancestry.com,” said Judith Daar, a bioethicist and clinical professor at University of California, Irvine, School of Medicine. “We’ve learned a lot, and the technology is marvelous and can be predictive and accurate, but we’re probably at a very nascent stage of understanding the impact of what the genetic findings are on health.”

Preimplantation genetic testing, or PGT, emerged in the 1990s as a way to study the DNA of embryos before they’re transferred to a womb, and the technology has grown more advanced with time. Federal data show it has been used in about 5 percent of IVF procedures going back several years, but many experts pin the figure as high as 20 or 30 percent.

In these cases, deciding whether to transfer an embryo or not requires weighing what a clinician is comfortable doing, as well as what the potential parent or parents want — and couples don’t always agree themselves. There’s also a third party to consider, one that at that point is just a frozen bundle of cells with no agency.

In interviews, a dozen experts from around the country emphasized that requests to transfer embryos with genetic anomalies are rare. In the large majority of cases, patients who want genetic testing on their embryos are doing so to select one with the healthy number of chromosomes or to avoid a genetic disease that has popped up in their families. And if all the embryos created through IVF have genetic defects, many women — depending on their age and financial situation — can go through another cycle.

But the experts also said they are seeing more patients asking for genetic testing on their embryos, which means that requests for transfers that involve ethical quandaries could become more common.

“This is a growing field,” Klipstein said. “There’s more awareness that you can test embryos. There’s more screening of patients who are thinking of parenting. The array of diseases that are available for testing is growing. The ethical issues have increased to an extent because some diseases are considered more health impacting than others. So where do you draw the line?”

In a paper published earlier this year, Daar, Klipstein, and their colleagues on the American Society for Reproductive Medicine’s ethics committee highlighted all the angles and inquiries involved with transferring embryos with genetic anomalies: patient autonomy, the rights and well-being of the offspring, and clinician choice among them. Their goal was to at least provide a foundation for how to think about the issues.

Though there are no U.S. regulations for these cases, some countries have stepped in. In the United Kingdom, for example, doctors cannot transfer embryos with abnormalities that may cause serious diseases or disabilities unless there are no other viable embryos.

The circumstances in these cases vary widely, but in some, physicians should not transfer the embryo, the committee wrote. Examples include when mutations seem guaranteed to cause life-threatening conditions or severe disabilities from an early age. Many physicians also say they typically won’t transfer embryos with an abnormal number of chromosomes; those embryos are more likely to fail to implant in a womb or to miscarry than they are to result in a birth, and any children who are born will likely have a range of physical and intellectual disabilities.

“Physician assistance in the transfer of embryos in this category is ethically problematic and therefore highly discouraged,” the ethicists wrote.

But beyond those scenarios, it’s difficult to draw clear guidelines.

Some people, often because of their religious beliefs, think that every embryo should be given the opportunity to be transferred.

And in other cases, patients will want to select an embryo with a certain genetic trait. Most frequently, experts say, this happens in the cases of patients who are deaf or have dwarfism and want to have children with the same traits. Such instances highlight the delicacy of rendering judgments about what’s acceptable in reproductive medicine and what’s not.

Some people in the deaf and dwarfism communities, for example, bristle at their DNA being described as having “genetic anomalies” and at the perception that their qualities are disabilities to be avoided. Others question why even severe disabilities are shunned instead of accepted. In an email, Howard Rosenblum, the CEO of the National Association of the Deaf, emphasized the importance of “reproductive liberty” — that deaf parents who want to use reproductive technology to bear deaf children should have that right.

The ethics committee said that in cases in which a child is expected to be born with a treatable disease or manageable condition, physicians are ethically right to transfer an embryo. But, the committee wrote, clinicians should also be able to refuse such a patient request. Doctors will often agree to move embryos to other clinics in those situations.

“It’s not a black-and-white issue,” said Dr. Mark Sauer, a reproductive endocrinologist at the University of California, San Francisco, and a member of the ethics committee. “You have diseases that are universally accepted as pretty awful to inherit that most people — not all — would agree would be best not to be transferred. But more commonly there are areas of gray.”

While she was trying to get pregnant four years ago, Samantha learned a relative carried a BRCA mutation, but she was so focused on having a child that she initially disregarded the news. But when a second relative found out she had a mutation as well, Samantha agreed to get tested. She was headed into her late 30s, and at least one relative had died of ovarian cancer in her early 40s.

Samantha found out she had the mutation in November 2013, and her doctors told her that with her family history, she needed to have her ovaries removed before she got pregnant. First, though, she went through three egg retrievals over the course of four months.

While working with an IVF specialist, Jessie and Samantha did at times question how far they were willing to go to have a child, and just how technical getting pregnant was becoming. Jessie’s priority was Samantha having her ovaries removed, but Samantha felt an urge to get pregnant, so both processes proceeded essentially in tandem.

“There was a lot of information, and it was overwhelming, and a lot of it was science-y,” Jessie said. “We were both a little like deer in the headlights.”

In March 2014, Samantha had her ovaries removed. Then they turned back to the embryos.

Samantha had only produced a few eggs during each retrieval, likely both because of her age and because the BRCA mutation limited production. Overall, the couple had four fertilized eggs.

Three of the embryos were chromosomally abnormal, however, and their reproductive endocrinologist told the couple that they wouldn’t lead to fruitful pregnancies. That left them with one embryo. It carried the BRCA mutation.

The good news was that the embryo was male. While the mutation increases the chances of certain cancers in men, the risk is not nearly as high as it is for women getting breast or ovarian cancer, a likelihood that sometimes leads them to have their breasts or ovaries removed prophylactically.

But transferring that embryo also meant Samantha and Jessie were keeping the mutation in their family, and that their son could pass it down to his children. And they knew they might run into some skepticism of their choice.

After Samantha and Jessie had made the decision to transfer the embryo but before the procedure, they were at a conference for the BRCA community. There, they met someone who was critical of people who would knowingly pass on the mutation to their children.

“Why would you do that? Obviously if you find out, you’re not going to transfer,” Samantha recalled the person saying.

Samantha and Jessie didn’t say anything, but Jessie said she remembers thinking, “Well, not obviously.”

“Right,” Samantha added. “Unless you only have one.”

Samantha and Jessie said they would have proceeded with the pregnancy if it had been a female embryo, despite the implications. Unlike Jessie, Samantha felt a deep pull to be a biological mother. And she felt that passing on the BRCA mutation — though doing so frustrated her — was not enough to overlook that.

“Having a baby, being pregnant, bringing a child into the world has been one of the purest, surest things I’ve known since I was a child myself,” she said. “I wasn’t willing to ignore that or let it go without trying everything we possibly could. It felt like it would have been devastating not to be able to do this.”

The couple’s reproductive endocrinologist, Dr. David Ryley of Boston IVF, said women with BRCA mutations generally accept the risk of passing it on to children.

“Think of it from her choice,” explained Ryley, who also teaches at Harvard Medical School. “She’s a BRCA positive female. Would her parents have discarded her if they had the choice? No. These women are surprisingly comfortable transferring these embryos.”

Ryley acknowledged that, were he to face requests to transfer embryos with other kinds of genetic anomalies, he would decline. It goes to show how, as the ethics committee wrote, clinicians should consider the different possibilities they might encounter; the committee also recommended that practices have written policies to share with patients.

“Here I am telling you that I’m OK transferring a BRCA-positive embryo, but not a trisomy 21 embryo,” Ryley said, referring to a chromosomal abnormality that causes Down syndrome. “And I get it, it makes you think.”

Members of the ethics committee said they weren’t sure how often physicians are asked to transfer embryos with genetic anomalies. One of the only data points is from a 2008 survey that found that 3 percent of IVF clinics offering PGT had had patients who wanted “to select an embryo for the presence of a disability.”

(There are two types of PGT: preimplantation genetic screening, which counts the number of chromosomes in each cell, ideally looking for 23 from mom and 23 from dad, and preimplantation genetic diagnosis, which is aimed at identifying specific genetic mutations. The latter is generally only done if there’s a reason to suspect the embryos might have the mutation, while the former is more common, particularly for embryos created with eggs from older women.)

In interviews, experts could often only recall a few relevant experiences from their careers. Carlos Guerrero, an embryologist and laboratory director at Fertility Specialists of Texas, said the practice does more than 600 egg retrievals a year and couldn’t remember a patient ever wanting to select for an embryo with deafness or dwarfism.

And Dr. James Grifo, the director of the New York University Langone Fertility Center, could only remember one pertinent case: a patient who had just one embryo, which would have resulted in a child with Down syndrome. At first the patient wanted to move forward, but later decided against it after meeting with a genetic counselor. Regardless, the clinic wouldn’t have performed the procedure and would have had to find another clinic to handle the transfer.

“When she understood what was going to happen, she changed her mind,” Grifo said.

The question of transferring embryos with known anomalies is not the only ethical debate at the intersection of genetics and reproductive medicine. Sometimes, an embryo will present as “mosaic,” meaning some of the cells shaved from the embryo for a biopsy have the normal 46 chromosomes, while others have an abnormal number.

Experts are finding that in some cases, those embryos develop into healthy children, perhaps because the abnormal cells die off or are partitioned into the placenta. The issue has led to concerns that some embryos that could mature into healthy children are being discarded, limiting options for prospective parents. And it’s an example of how, as the ethics committee wrote, “genetic testing of embryos can produce results that are indeterminate, inaccurate, or both.”

“What if you test five cells and one cell comes back 47 XY with one extra chromosome 21?” asked Dr. Owen Davis, an IVF expert at Weill Cornell Medical College and former president of the American Society for Reproductive Medicine. In that case, that one cell would indicate the child could have Down syndrome, while the other four would indicate a healthy child.

For all the heartache and stress that went into getting pregnant, Samantha’s actual pregnancy was quite easy. She delivered her and Jessie’s son two weeks after her due date.

They’re not sure yet how they’re going to tell their son about the mutation — perhaps when they tell him about how he came to be, or when he learns about DNA in school. And while they occasionally think about the mutation, they are much more focused on every other part of their son.

“From the moment he came out,” Samantha said, “I couldn’t believe how beautiful he was.”