SART Fertility Experts: Carrier Screening and Fertility Care

In this episode of the SART Fertility Experts podcast, host Dr. Kelly Lynch welcomes Teresa Cacchione, MS, a clinical genetic counselor at RMA of New York, to explore the evolving landscape of carrier screening. They discuss the importance of genetic screening for X-linked and recessive conditions, differences between panel sizes, ethical considerations, cost, timing, and how screening supports informed reproductive choices. Learn how carrier screening aligns with ASRM guidelines and empowers patients—especially those pursuing fertility treatment or using donor gametes—to plan confidently and proactively.

Hi, my name is Dr. Kelly Lynch from the SART Fertility Experts Podcast. My guest today is Teresa Cacchione, MS and Clinical Genetic Counselor at RMA of New York. I am so glad to have her here today and our topic today is carrier screening.

Thank you so much for joining me today, Teresa. Thank you for having me. Teresa, many of our patients have questions about whether or not to consider genetic screening.

Can you talk to us a little bit about the different types of screening panels that are available and why a patient might choose to have this testing done? Sure, definitely. So, I mean, there's a couple of different indications where patients might consider genetic testing. The one that I think we come across most frequently in the setting of reproductive endocrinology or obstetrics is carrier screening.

So, carrier screening is looking for risks for a particular individual or couple of what are called X-linked or recessive genetic conditions. And this is a really specific class of genetic disorders where, you know, the risk may not be apparent just from looking at the patient's own personal family or medical history. Typically, you know, carrier status is silent, meaning that someone can have the for recessive or X-linked genetic disorder in their genes, but not know it.

But then, you know, if in the case of recessive disorders, if their partner carries the same condition, or in the case of X-linked disorders, if the individual or couple has a male child, then we can suddenly see the disease pop up in the family. And this is borne out in multiple studies that have shown that for recessive and X-linked conditions, you know, 80% of individuals who are born with those disorders don't have any family history. So, I think that, you know, the biggest thing we often see, right, as patients come in and we talk about the option of carrier screening, and the first thing we hear is, well, I don't have any family history of genetic disorders.

And my reply is always, that's exactly the point, right? We are screening for things that we might not know about until it shows up in that generation. That's exactly the conversation that I have, as well as most people don't have any family history. And so, it is, it makes it a little bit harder conversation to have.

Definitely. Try to talk to them about the possibilities, but our goal is to try to help identify those people who might be at risk before they conceive. Exactly.

And the goal is really to give them the most number of reproductive options, right? Be able to have those conversations before, ideally before, you know, we're in a situation where a pregnancy, you know, we're sort of making decisions about whether or not to continue a pregnancy or whether or not to do additional testing, you know, on a pregnancy. So, the, you know, the goal is to have that testing done, you know, ideally preconception, but of course, not every pregnancy is planned. That's not always possible, but, you know, and if pregnancy has already occurred to try to get it done as early and as quickly as possible, you know, in the beginning of the pregnancy.

Right. And I try to tell my patients, this is empowering you. It's giving information to help you make decisions about what you want to do, but it's not a requirement, at least in our practice here.

It's often required. Yeah, definitely. I think that, you know, with carrier screening, you know, we recommend it, right? Of course, you know, I, being part of a large reproductive endocrinology clinic, it's definitely in New York City.

It's definitely something we recommend, but genetic testing is always optional and we absolutely have some patients that decide, you know, to decline after being counseled by our doctors or nurses about the potential benefits. I think, you know, uptake definitely, or whether or not someone wants to proceed can really vary depending on a lot of things, you know, depending on if they're pregnant already or depending on if they're planning fertility treatment where they might have more time and more options to consider based on the results. And also, you know, varies depending on personal preferences, religious or ethnic considerations, et cetera.

Can you comment a little bit about the size of the panels? And it seems like they're getting larger and larger. Yeah. Yes, this is a sort of a double-edged sword a little bit in genetics right now, especially for reproductive genetic counselors.

So, you know, historically carrier screening was very targeted. So it typically was targeted either towards conditions that seemed most relevant for particular ethnic backgrounds. And this, you know, was based in practical considerations for the most part.

Genetic testing used to be very labor intensive and very expensive. So we had to identify the people that were at the highest risk and screen for the conditions that were most severe and had the highest carrier frequency. And that sort of used to be the approach.

But there have been huge changes in genetic testing technology since then. You know, we now have something called next generation sequencing and a number of different other technologies that have made genetic testing much higher thoroughput, which means that you can screen for a lot more genes and a lot more changes within those genes simultaneously on the same blood sample and has made testing much less expensive in comparison to it's still not, you know, inexpensive, but in comparison to what it used to be. So, you know, now we have the ability to be screening for multiple diseases and causes of those diseases simultaneously, easily, much, you know, in a much more affordable fashion.

And simultaneously, there've been a lot of studies that have shown that, you know, maybe we're not the best at actually self-identifying our own ethnic backgrounds. There was one study done where 80% of the individuals who were found to be carriers for conditions that were traditionally associated with one particular ethnic group had not reported that ethnic group as their sort of known background. So I think, you know, our knowledge of sort of what testing is most appropriate for different individuals and that in combination with the technology getting better has meant that instead of doing targeted testing for just a handful of conditions, we're now screening for a larger number of conditions simultaneously and taking more of what's called a pan-ethnic approach, meaning that we're not really thinking about that individual's ethnic background.

We're thinking about, okay, in society as a whole, what are the most common conditions for individuals to carry? So that, I think, has been sort of the very well-motivated and positive aspect of the advances in our technology and understanding. On the flip side, you know, I think we've gotten a little carried away, you know, potentially between, I think, you know, different individuals wanting to offer more and more testing and different laboratories wanting to sort of offer the best thing they can offer. And there is evidence to show that, you know, once we get past a certain number of conditions, the clinical utility, meaning the usefulness of the test, starts to go down.

You know, unless two individuals who are conceiving are related or have a known family history of a particular disorder, the chance of them, you know, sort of overlapping for some more rare conditions starts to become incredibly low. So I think we're at a point in the field right now where we're trying to decide where is that cutoff point. So where are we sort of addressing what's the highest risk for the most number of individuals without suddenly screening for way more conditions than we really need to be in the general population.

And perhaps causing some anxiety. Absolutely, yes. And a lot of labor and time for all the health professionals involved.

Yeah. As a genetic counselor, are there any diseases that feel like everyone should be screened for? Yeah, I mean, I think that the classic ones, I think, still hold. You know, I think the diseases that were first screened for, you know, pan-ethnically for everyone were cystic fibrosis, spinal muscular atrophy, sickle cell anemia, and other hemoglobinopathies and Fragile X. I think those hold.

Those are definitely still very important and relevant for everyone. But I think after, you know, many years now of running a more pan-ethnic panel, there are certainly conditions that we see across multiple ethnic groups that maybe weren't traditionally screened for as much. Non-syndromic hearing loss is a very common one that we see quite frequently.

And that one is also a little bit debated because it is a condition that's treatable, that doesn't impact lifespan or intelligence. So there's been some debate whether or not it should be included on the panel. But it is extremely common in the general population, that carrier status for that condition.

And we also see familial Mediterranean fever a lot. That, I think, is another one that makes sense. And, you know, a number of the conditions like Tay-Sachs and other disorders of that nature that were traditionally considered diseases that, you know, were most relevant to individuals of Ashkenazi Jewish ancestry, I will say, appear to be more pan-ethnic than we originally thought.

We see them a lot in just the general European population as well. So I think, you know, that more pan-ethnic approach has made a lot of sense and has really made a positive difference for a lot of individuals at this point. I agree with you.

And I really think it just helps people start the conversation as a couple and then with their families about, we might carry this disease in our family, other people might want to be tested as well. What are the implications if we have a child with this condition? It just helps people to know a little bit more about this. And it's very difficult though to sometimes see the benefit always of this, but it helps people at least be aware of what's out there.

And would you be willing to just talk a little bit about the implications of, say, cystic fibrosis for a child and the family and why it's so important to offer this screening? Absolutely. Yeah. So for a condition like cystic fibrosis, it can be a bit of a range of severity, but traditionally that we started screening for this condition because of the more severe form of the disorder, which is called classic cystic fibrosis.

And basically it's a disorder where the mucus that lines our lungs and our gastrointestinal tract, reproductive tract as well, basically the body can't regulate the thickness of that mucus the way it's supposed to. And it causes blockages of those different tracts and can attract bacteria, particularly in the lungs. So individuals with cystic fibrosis typically will be very high risk for recurrent lung infections and severe infections like pneumonia and other rare infectious bacteria also typically have a lot of difficulty digesting food, tend to be very malnourished, you know, without the help of digestive enzymes that we call it pancreatic insufficient cystic fibrosis, where the pancreas can't really do its job because of that accumulated mucus, as well as there can be reproductive impacts as well.

Typically, historically cystic fibrosis, because of the recurrent lung infections and the scarring that results that does over time, start to restrict pulmonary abilities and all of that. Traditionally, the lifespan, you know, has typically been a very short and significantly shortened lifespan about 40 years old, you know, is the typical lifespan for most individuals with CF that has gotten a lot better. There are newer, you know, sort of medications, gene therapies out there that have made a big difference.

But of course, it is not a disease that is currently curable. And it is one of the more conditions, more common conditions pan-ethnically for individuals to carry the carrier frequency. So the likelihood of being a carrier is less than one in 100 for most ethnic groups.

But it is particularly common that carrier status in individuals of European ancestry, so about one in 25 on average carrier frequency. So if we, you know, find out that both the egg and the sperm source are carriers for the same condition, and I say that instead of the patient and the partner, because, you know, in reproductive endocrinology, we are often also looking at donor egg, donor sperm pairings, you know, when we're looking at this as well. If the egg and the sperm source are both a carrier for the same thing, you know, both a carrier for the cystic fibrosis, then we have a couple options to consider.

You know, if we're preconception, theoretically, we could, you know, use in vitro fertilization and something called preimplantation genetic testing or PGT to basically test the embryos prior to them being used for pregnancy and making sure that the embryos that are at risk that have inherited the cystic fibrosis, you know, disease-causing change from both parents, make sure those embryos aren't used for pregnancy. So we can use IVF as a selection mechanism. If someone doesn't want to do IVF or if pregnancy has already occurred, they can consider diagnostic prenatal testing, either in the form of a CVS at the end of the first trimester or an amniocentesis in the second trimester to elucidate the status of that pregnancy.

You know, is it negative, a carrier like the parents, or affected at risk for symptoms? And I think a lot of people think that, you know, we would only use those methodologies with the goal of potentially not continuing the pregnancy. But I do think they do have a role, you know, for individuals who may not, you know, be comfortable with that option. Also in just anticipatory planning, right? Having that knowledge prior to birth can be so important for, you know, finding that, finding out that, you know, an infant is affected with cystic fibrosis in the newborn period is possibly the worst time, you know, to find out that information if you can avoid it, just because, you know, the newborn period is so stressful for the parents to begin with.

I think having that knowledge ahead of time and being able to set up appropriate care providers and learning about the condition and everything can be really helpful. So I think that, you know, that knowledge is really the goal of carrier screening is to give patients knowledge that can help them make reproductive choices, even if it's one that really wouldn't impact their pregnancy planning, the knowledge that they can have to help them after birth as well. I totally agree with you, Teresa.

I try to educate my patients about this as well, that the goal of this testing is going to help you be a better parent, be better prepared for the child that you're going to have and know exactly what care that they might need, you know. So if they are carriers and they do decide to proceed without PGT, they can at least make sure that they educate themselves about how their child can receive the best care and they can be prepared for that. And so I really don't see too many downsides to knowing if you're a carrier for cystic fibrosis or if you're both carriers for cystic fibrosis, because you really do get to plan ahead, you know, about what may happen and you can really make sure that your child is going to have everything that they need from the start as opposed to having to try to make that diagnosis in the newborn period, which is difficult.

You also mentioned donor eggs and donor sperm, which of course in reproductive medicine, we help many patients with fertility problems with donor eggs and donor sperm. Can you talk about how carrier screening can be helpful in those situations? Yeah, so it can be really helpful in, you know, when we're helping a patient choose an egg donor or sperm donor, you know, they're using a lot of factors to make that choice. There are some personal preferences, there are some medical or biological preferences such as blood type or different infectious disease statuses like CMV.

But one factor that goes into it is wanting to make sure, you know, we've often done recommended carrier screening for, you know, the individual who's our patient, be they an egg contributor or a sperm contributor. And in choosing their donor, they want to make sure that whoever they're choosing does not overlap with them in terms of carrier status. And I think that that ends up being particularly relevant for, you know, our egg and sperm donor selection because there are choices, right? If they do overlap with someone that they're interested in, they can theoretically choose someone else, right? Which is not always a consideration, right, when we're working with couples using their own gametes.

So, you know, I think that we want to make sure that if they have that choice, that it's one that is safe and minimizing risk as much as we can where we can. And if, you know, there's a donor that they are really, really, really sort of attached to and really, really want to use, but there is a joint carrier status, we could consider PGT if we really wanted to. But, you know, both diagnostic prenatal testing and PGT require knowing about the joint carrier status ahead of time.

Those tests are targeted. We can't sort of go looking for things in the way that we do on carrier screening or on tests on blood. We have to already know what we're looking for.

So, the goal is to go into, you know, a pregnancy with as much, with all that information already known. Right. It's definitely helpful.

What I found is interesting, some of the sperm banks offer search tools that help you. You can put in the disease that you're a carrier for and choose select donors that are negative for those conditions to make the search a little bit easier. It's been immensely helpful for patients, definitely.

Absolutely. And I think, you know, it's sometimes the choice can be overwhelming for patients. So, this helps narrow down the choices a little bit.

Absolutely. It's been helpful and it'll, you know, it's a good way to help, you know, we want people to have healthy pregnancies. Well, this is one more thing that we can do to help improve the chances of a good outcome.

Definitely. Are there any other thoughts for patients that you'd like them to know about carrier screening? One of the questions I do get asked from time to time is, my DNA going to be out there? Is someone going to be able to, you know, is my DNA going to become part of a database if I subject to this testing? I mean, the answer to that is no, right? That would be against multiple guidelines. Most, you know, patients can read in their consent forms that they're signing for the labs about different laboratories have different policies about what they do with remaining DNA.

I know in New York state where I practice, DNA is discarded automatically after 60 days. That is a rule. But no, I mean, ultimately the testing is being ordered for a specific set of conditions.

The lab is not analyzing that individual's DNA outside of the genes that are being targeted. So, you know, there isn't additional information on individuals sitting out there somewhere in a database. You know, obviously most, and this is the case with most testing that's performed anywhere, you know, de-identified results are often used for research.

So the lab can say, you know, X percent of the people we tested were a carrier for Tay-Sachs or X percent were a carrier for this condition, just for sort of the sake of scientific knowledge. But nothing, all of the laboratories that I'm aware of, you know, will not sort of do anything that could potentially compromise revealing a patient's identity. That would be against HIPAA guidelines for sure.

Right. And do my best to reassure patients of that, but I think it's nice to hear from one of our genetic counselors too. I think one thing I would love patients to know and a common question I get is patients often ask, you know, or are often concerned that the testing they're doing is going to reveal risk to their own health.

Right. So they're often concerned that it's going to tell them about cancer risks or risks for Alzheimer's or Parkinson's or things like that. So we often, you know, have to reassure patients that the conditions that are being tested are curated for a very specific reason.

The labs choose what genes go on there. And the goal is to assess reproductive risks. So risks to the next generation.

Right. So the testing being run, we're not testing for anything dominant. So dominant diseases are diseases where there is really no carrier status.

If there is a change in that gene, you personally will, you know, sort of be at risk for health effects from it. So that, you know, comes down to things like Huntington's disease and the breast cancer genes, BRCA1 and 2, and other things that are similar. So those genes are, you know, dominant conditions are not included on carrier screening.

So the carrier screening is not intentionally going to be revealing anything about the personal health of the individuals being tested. There are a couple conditions on there where we might accidentally find out about minor increased risks. So that is something that we like to mention in pre-test counseling.

There are a couple of genes that carrier status comes with slight increases in cancer risk, but it's on there because the recessive form of the disease is very severe. So it's worth, you know, finding out about the carrier status to rule out risk. There are every once in a while, we'll actually pick up someone who has a recessive condition and didn't really realize it.

It's usually conditions that have milder versions that could have gone undetected. So, you know, that will happen, but the goal ultimately is not to sort of be identifying anything about the individual being tested on health. And whenever possible, when we're doing that type of testing, it requires additional pre-test counseling.

Exactly, exactly. So we would typically not run BRCA analysis or Huntington's testing or anything like that as part of a general reproductive screen. That would be done after consultation with an MD specializing in that particular area or with a genetic counselor specializing in that area who would review the family history, discuss the benefits and risks of testing and recommend testing that's most relevant based on the personal and family history.

That's a diagnostic testing approach. It's very customized. So we would not do that as part of just a general screen.

So I have one last question for you. So when we see new patients, we offer this screening, but there is a cost to it. It's covered by insurance.

What do these panels typically cost in your experience? And does insurance ever cover the cost of screening where you are? Yeah, great question. I think it can vary by laboratory and by contract. So the contract between the laboratory and that hospital or that doctor's office, depending on volume, but I would say on average, if not covered by insurance, I'm usually seeing carrier screening run between $250 and $500 per person being tested.

So per couple, that could be, you know, $500 to $1,000 for testing. You know, I think that that definitely is still a fair amount of money. Although I think historically being able to look back at what genetic testing used to cost, it's actually relatively inexpensive, but absolutely it's still a significant amount of money for a lot of people.

I will say that some insurance companies will cover it. I see a lot of variation in that between different plans. There are definitely some major payers in the country that do not.

And it is, I think, a major goal of genetic counselors and obstetricians and the carrier screening laboratories to really make a case as to why this testing is so important. And ultimately, you know, not that we'd like to put things into dollar signs, but ultimately, you know, sort of will help prevent the occurrence of diseases that are so significant. But I think that, you know, we're seeing a range, definitely.

I think that we have a long way to go in terms of sort of making a case to the insurance companies about how important this testing is. And in terms of a new patient or couple that you're seeing, do you recommend tandem screening or sequential screening? What's your preferred? I think it depends on their goal, you know, or their timing. I think if they're already pregnant or if they are trying to move forward with fertility treatment quickly, then tandem testing or concurrent testing makes the most sense because typically, you know, carrier screening results take about two to three weeks to come back per person.

So if they're doing it sequentially, so, you know, typically, we would recommend the female individual or the individual who is contributing eggs to go first because individuals with egg cells can carry X-linked disorders. And ultimately, you want to make sure you have screened that pairing for X-linked conditions. So a lot of times, you know, egg contributor will go first, and then we'll screen the sperm contributor second for only the recessive conditions that the egg contributor carries.

But that ultimately means that getting all results back will probably take at least six weeks altogether. Assuming everyone had blood drawn immediately, and there wasn't counseling time and everything. And that's a long time if an individual has already conceived or is trying to move forward quickly with fertility treatment.

I would say, you know, in my practice in reproductive endocrinology, it is very common for them to do screening together because most of the patients I'm working with are trying to get moving very quickly. That's a great point. Thank you so much for taking the time to meet with me today and review the ins and outs of carrier screening for patients.

This has been a really helpful conversation. Thank you so much for joining me for this episode of SART Fertility Experts, the podcast for people trying to build a family. And again, this was my guest, Teresa Cacchione from RMANY.

Thank you and have a great day. Thank you for having me. The information and opinions expressed in this podcast do not necessarily reflect those of ASRM and its affiliates.

These are provided as a source of general information and are not a substitute for consultation with a physician.