HD-Free Embryos on the Rise
The Future of IVF for Rare Diseases
In-vitro fertilization offers couples an opportunity to end HD for future generations.
Jessica Ryniec, M.D., is a specialist in in-vitro fertilization (IVF). She sees patients who are pursuing IVF for infertility and to identify embryos that do not carry a certain disease gene. She practices at CCRM Fertility in Boston, Massachusetts, where partial or full coverage of IVF is mandated by state law. This places her practice in an ideal position to see patients with rare diseases.
Tell me a little bit about your work in genetic testing for patients at risk for rare disease genes?
We do carrier testing through a blood test when the couple first comes to see us to find out if they carry the same disease gene as a family member, such as cystic fibrosis or spinal muscular atrophy or HD.
Sometimes people know ahead of time that there is a specific gene in their family—often these are dominant genes like in Huntington’s. But we also recommend genetic carrier screening for all patients to see if their partner and they carry the same recessive genes, because that would also be a risk. That is what we test with our 175+ gene panels.
In performing these blood tests, the labs need to make a probe specific to the patient’s genetics because even though we know what genes are associated with a disease, there can be different fingerprints in different people. So, there is an evaluation to see what exact gene this person has.
Our patients will have chosen ahead of time whether they want to know what we find that in testing or not. Then we proceed with the egg retrieval and the genetic testing of the embryos. For rare disease screening of monogenic disorders, we do pre-implantation genetic testing (PGT-M) of the embryos.
What are the risks in IVF?
The risks to the mother are very, very low. But there are other risks inherent in the IVF process in order to be successful. Even naturally, a lot has to happen for an embryo to get to the point of implanting and becoming a baby. But there are slightly elevated risks of embryo damage in vitro versus in the womb in rare disease IVF, because we have to manipulate them a little bit in the lab when we do the fertilization via intracytoplasmic sperm injection (ICSI). This is opposed to conventional IVF where we just put the sperm and egg in proximity to one another.
Then there are procedures like assisted hatching, where a small hole is drilled in the shell of the embryo to help it to grow and expand, and then there is the biopsy itself to test for the gene. But all these risks are usually pretty low.
If the couple wants to freeze eggs or embryos for the future, there are also some risks in freezing and warming them. Not all eggs or embryos will necessarily survive that process, but about 95% will, I’d say.
There used to be a much lower survival rate for eggs compared with embryos, but now they are getting pretty close. Embryos still do a little bit better because there are multiple cells instead of just the one cell and because we know more about the embryos, since they’ve already fertilized and the cells have undergone considerable cell division.
Can you test eggs for the HD gene?
No, because they are single-cell. To do a gene test, you have to remove some cells from the embryos, test them and then discard those particular cells. When you finish, typically about four to five cells from the outer part of the embryo are involved.
With rare disease testing, where are the pain points, the costs that might not be covered by insurance, the biological or technological difficulties with doing this?
While insurance covers IVF for infertility in my state and a few others, sometimes this doesn’t extend to rare disease IVF, and even when it does, the genetic testing for a specific gene disorder may not be included in that. Fortunately for my patients, many times it does when it is for a specific gene disorder—it really it depends on the specific insurance companies.
A single cycle can be up to $20,000–25,000, depending on how much medication someone needs. Ultimately, costs can depend largely on the characteristics of the person, because some people might need multiple cycles for us to find normal embryos, whereas others might just need one.
Why is this so expensive?
A large part of it is the medication and, of course, there are multiple ultrasounds and blood draws. There’s a procedure with anesthesia to retrieve the eggs, so you have surgical site and surgery fees, and then the lab fees to fertilize the eggs, grow and monitor the embryos, and do the biopsies on the embryos. Then there is the implantation procedure. So, there is a lot that goes into it. These high costs don’t look to change anytime soon, because you need all those components.
Do you know of specific advocacy groups that have worked or are working to get more IVF covered by insurers?
Resolve New England is probably the biggest IVF advocacy group in Massachusetts. There’s the New England Fertility Society, and Resolve, which does a lot of advocacy as well. And then, of course, patients and doctors can be huge advocates when they can make their voices heard by legislators.
Do you see any risks of the Dobbs decision changing IVF opportunities in some states?
I think it’s a very real concern, because IVF came about after Roe v. Wade. So IVF wasn’t really thought of when the state bills were written. There are definitely a lot of potential impacts that it could have, especially in states with those early personhood bills, because those define life at fertilization, which is near the beginning of the IVF process.
So, the questions that need to be addressed may be: do we have to limit the number of embryos that we make, or the number of eggs that we fertilize? And what do we do with embryos that are additional to the one that’s initially being transferred? What happens when no one has to pay for their upkeep forever, but the law says you can’t discard? If something happens to an embryo in the lab, is that technically manslaughter?
Some of it sounds crazy, but it’s definitely a concern. I doubt it is the intent of many legislators to ban IVF or influence current practice, but it could happen unless intentional exceptions are written into the law.
I think that the infertile population has some very, very fierce advocates that can make change happen. We saw this happen in Nebraska recently, when they were trying to put forward their personhood bill, and the parts that would affect embryo use and storage were taken out of the language. So I think this is a time for awareness and advocacy on a state level. And that’s why it’s really important for everyone to talk about what these possible impacts are and craft the laws to protect IVF.
Finally, tell me what led you to this line of work?
I come from a big family—four brothers and sisters—and family has always been the most important thing to me. And I think this field is such a wonderful balance of medicine and human compassion because we are taking everything we know about the menstrual cycle and our hormones and our bodies and altering or adjusting it to improve outcomes.
Then there are also a lot of psychological and mental health issues that go with this obviously difficult diagnosis of infertility, and for those with genetic concerns, that can be magnified!
There’s also surgery and procedures involved, and as a very hands-on person, I enjoy that. So there’s just a really nice balance of multiple things that I’m interested in. Best of all are those special moments I have to be a part of people’s lives, given how important family is to me. Being a mom was very important to me. I couldn’t imagine not being able to have a family. So having my own family and helping people have theirs just feels really perfect. It all fits together.
Will the Dobbs Decision Impact IVF or Embryo Research?
The country’s two major political parties came to blows, as is increasingly the pattern, over the Supreme Court’s Dobbs decision in June, 2022. With the abortion decisions sent back to the states, legislators have been busy assessing their trigger laws, and whether they will establish that human life should be protected at conception or at a certain number of weeks of gestation, and under what circumstances exceptions should be made. For many states, their laws automatically protect abortion rights clear to birth. Others establish more moderate cutoff periods, while still others ban abortion altogether.
Some in the HD community have raised concerns about whether, in pro-life states, the rights to IVF will be protected. We asked Tennessee Senator Richard Briggs, who is a physician and a legislator in a trigger law state, to offer his thoughts on whether the Dobbs decision will impact these rights or have an effect on embryonic research. Senator Briggs has been involved with CEOs of the major medical centers to help assure that the performance of medically necessary abortions are not thwarted, while waiting for trigger law revisions when the General Assembly reconvenes in January.
His comments on the Dobbs decision’s impact on current abortion, IVF practices and embryonic research:
Quite frankly, I’m not sure anyone thought that Roe vs. Wade would be reversed by the U.S. Supreme Court. Of course it was, and what our law in Tennessee basically did is revert to the 1970 law that was in place before Roe vs. Wade.
On things like rape, incest, mother’s health or severe fetal deformities, I think the trigger law needs to be modified to enable these exceptions right away. Then the debate can go, if somebody didn’t want to be pregnant, is an elective abortion allowed and when—at six weeks or 12 weeks or 16 weeks?
However, I am one of 132 legislators, and we have I think a very pro-right-to-life legislature. I’m certain there will be an entire spectrum of opinions. What I think is reasonable and a private medical issue, someone else may view as a crime.
“Regardless of the abortion backdrop, I don’t see any forthcoming change in IVF or use of embryos for research. I see it as a very separate issue from abortion. I think that we have done most of what we’re going to do about dealing with embryo research, as well as how to handle aborted fetuses. People can always file bills, but I don’t hear anyone talking about IVF or embryonic research being on the table.”
– Senator Richard Briggs
Meet Morgan, Matt and Addie Gothard
Elementary school teacher Morgan Gothard is an as-yet untested young woman who is at risk for HD. In 2021, she and her husband, Matt Gothard, an accountant with The Cutter Group, LLC, received a Help Cure HD grant for one cycle of IVF. Today, they are caring for a healthy, scrappy Addie Gothard as she approaches her ninth month of life.
We asked the couple to talk with us about their experience. As Addie was keeping Mom busy, Matt recounted their IVF journey from concept to conception to sitting here today with their HD-free baby girl.
How did you first learn about the HD risk?
We have been married almost five years. About a year after we married we found out that Morgan’s dad had HD.
He is a patient of Dr. Claassen’s, and Morgan goes in every year for testing as a participant in ENROLL-HD. Through getting more familiar with HD groups, we found out that there were new grants available through Help Cure HD, a group founded by Allie LaForce and Joe Smith.
We applied, and were one of the first ones to get a grant! This was at the end of 2019, but then COVID kind of shut things down. So we started our first IVF cycle in August
How does the grant work?
The grant pays for egg retrieval and genetic testing, plus all the medications you need along the way. The testing is blind, so the couple doesn’t know if the HD gene is found in any eggs or not. They also test for a lot of other common genetic abnormalities.
We started with shots to prepare Morgan for the egg retrieval. They retrieved eggs, did in-vitro fertilization and sent the eggs for genetic testing before implanting them. We were kind of a healthy couple and didn’t have any fertility issues, so they just implanted one of the embryos that came back as candidates.
Unfortunately, Morgan had a miscarriage at 10 weeks. About six months after that, we went through a second cycle, everything was great, and that embryo became Addie.
What were the biggest challenges during this process?
Probably all the shots. For about three weeks before each egg retrieval, Morgan got three shots a night so multiple eggs could be harvested at one time. That way, when they do the retrieval they are not just pulling one egg. Then there was one hormone shot a night for the first 12 weeks of pregnancy, plus estrogen patches to help make sure her body accepted the implanted embryo.
Fortunately, my sister is a nurse and was willing to come every night and deliver those shots. After that it was “pregnancy as usual”! Of course the next question is, do you plan to do it a second time? We do have some eggs that are frozen. We have to kind of recover a bit, let some time pass, then we probably will.
Tell me more about Help Cure HD. Do they raise all the funds for grants or does the Smith/ LaForce family donate as well?
It is both. We just went to the gala in Houston, and I think they raised over a half a million dollars at that one event. They are definitely growing, and they want to help more and more people each year.
Do you see an upturn in advocacy for insurance coverage, since the waiting list for grants will likely only grow as more couples are successful?
Help Cure HD is doing advocacy work on a national level. We just talked with Nicki Sims, who heads up the grant program for Allie and Joe. She is pushing for legislation to require insurers to help cover the costs of IVF, genetic testing, and the other expenses. It’s hard because any one insurer is unlikely to see the long-term cost-benefits of a healthy adult versus one with active HD, but system-wide, of course, it pays for the costs of IVF to be covered.
Any final thoughts on the potential IVF has for others at risk for HD?
Of course we are huge fans of IVF for HD! This is the one way to ensure that generations down the road don’t have to worry about Huntington’s disease. It’s simply a great thing, given that there’s no cure at this point in time.
Help Cure HD
Help Cure HD was founded in 2018 by TNT NBA sports commentator Allie LaForce and MLB pitcher Joe Smith, who lost his mother to HD in 2020. Together, they created the Help Cure HD grant program in 2018 and have, to date, provided nearly 100 couples a grant to cover the expenses for IVF, including medications and PGT-M genetic testing. Nearly 20 women have given birth to a child who is HD-free with a growing number of pregnancies each day.
“We just held our annual gala in Houston, where we raised over $500,000 toward funding our grant program,” said Nicki Sims, Director of Grants and Clinical Relations at Help Cure HD. “With these kinds of contributions, donations from our corporate sponsors and clinical sponsors, the funding has grown tremendously. In 2021, we awarded 54 grants, and so far in 2022, have awarded 23, and are about to award for cycle two of 2022 in a few weeks.”
Help Cure HD officially covers all the costs of one cycle of IVF, all the way until the patient is released to their obstetrician, eight to ten weeks following a successful transfer. In about 40% percent of the cases, the first cycle may not be successful in producing a baby. For these patients, Sims says negotiations and generosity on the part of clinicians sometimes fill the gap.
“Everyone wants to see a success for these couples,” she said. “We will advocate for them with their doctors, and there are certain doctors we work with who have gone out of their way to discount rates and make that second cycle possible. We could not do what we do without them.”