Hi everyone, my name is Nour Chanouha. I'm a genetic counsellor at the University of Iowa Healthcare and I'm so excited to be hosting this SART Fertility Expert episode on genetic screening of donor sperm. I have with me here Katherine Hornberger.
Katie is a genetic counsellor, a board certified and multi-state licensed genetic counsellor with over 10 years of experience in assisted reproductive technology. Katie currently serves as a genetic counsellor at Seattle Sperm Bank and as a genetic counselling advisor at Core Fertility. Prior to joining Seattle Sperm Bank, Katie worked for a world-renowned IVF center as well as pre-implantation genetic testing laboratory.
Katie has gone through a fertility journey of her own and hosts a YouTube channel dedicated to explaining genetic concepts related to fertility and conception. Katie, welcome and thank you for being with us today. Thanks so much for having me, Noor.
Okay, so let's delve right in. My first question is kind of related to the donor genetic screening process at your meet bank. Can you walk us through that donor genetic screening process, really from initial intake to final eligibility determination? Yes, absolutely.
And just as I start to dive in here, I do want to share the views that I'm sharing are my own and don't necessarily reflect the views or policies of my employer or any of the affiliated organizations. But yeah, let's talk about at a typical gamete bank, a sperm bank and egg bank, kind of what all occurs in the screening specifically related to genetic screening. And there's a lot that needs to happen before you even get to genetic screening.
You know, whether it's an egg or a sperm donor, you've got to look at their fertility, semen analysis for sperm donors, a few different tests for potential egg donors. But where genetic screening really starts is with the family history. Okay, that's the first thing that most banks are going to look at.
They're going to ask donors, applicants to complete a family history form to meet with somebody at the bank to go through their family history in a really detailed sense. Most reputable banks are going to ask about the donor, whether they have any medical diagnoses. They're going to ask about the donor's children, if the donor has children of their own, donor's siblings, donor's parents, donor's aunts and uncles, cousins, and donor's grandparents.
So this is going to be a detailed at least three-generation family history or pedigree, as we call it in genetic counseling, looking for any medical diagnoses in that family history. And then we use guidelines from the American Society of Reproductive Medicine to say, does this donor meet eligibility based on this family history? So that's kind of the first part of genetic screening is looking at what can we glean from this family history? Does it look like there's a high chance of a heritable condition in future children of this donor or not? And then the second part of genetic screening is going to be actual genetic testing. So using a blood sample or a cheek swab sample from the donor, running some genetic testing to say, okay, we've got one piece from the family history, but is there anything we can't tell from looking at the family history? And the reason we do these two different approaches is because usually the things you find on genetic testing are things we weren't going to be able to identify on family history and vice versa.
So when we talk about genetic testing of donor applicants, the standard genetic tests that most banks are going to run are one, a karyotype. It's also called a chromosome analysis. And this is a test that quantifies how many chromosomes are present and looks at how they're arranged.
And it usually comes back pretty binary, like pass, this donor has a typical karyotype or chromosome analysis, or disqualification. There is a chromosome or something atypical in this karyotype or chromosome analysis that means the donor might have an increased risk to have children or pregnancies with chromosome differences, maybe an increased risk of miscarriages. So that one's pretty straightforward.
The other test that's standardly run at most GAMI banks is a carrier screen. And the carrier screening, which probably many intended parents or individuals who've already sought fertility treatment have become aware of, is typically looking at hundreds of different genetic conditions. Most of them are conditions where both the egg source and the sperm source have to be carriers of that same disease in order for there to be an increased risk to have a child with that condition.
So this test, most donors will actually come back positive, meaning they'll be found to be a carrier of something, one or more genetic conditions. But the way you want to think about these results is you want to interpret them with both the egg and sperm sources results hand-in-hand to compare and to check to see if there's any overlap of those conditions. So those are the two typical panels or genetic tests you'll see run by most GAMI banks.
So whenever you're evaluating those donors, how do you approach those what we call like multifactorial conditions like autism, diabetes, heart disease, where, you know, there's both genetic and environmental factors that are contributing, right, to those conditions? I mean, you mentioned ASRM or the American Society of Reproductive Medicine kind of guidelines. Do you follow these strictly? If not, how do you incorporate those? Yes, multifactorial conditions, conditions for which there's both a genetic component as well as environmental factors or triggers that lead to the disease, they can be really challenging because there can be really severe multifactorial conditions like maybe multiple sclerosis. There can be much more mild multifactorial conditions like maybe hypertension and a 70-year-old grandparent that's well-controlled with lifestyle factors, you know.
So we want to think about each of these differently. And I would say, yes, most reputable GAMI banks are definitely going to strictly follow ASRM's guidelines. And oftentimes they layer on top their own protocols or guidelines because ASRM's criteria, they can be pretty ambiguous.
They leave a lot up to interpretation. So, for example, ASRM's guidelines say for something like ADHD, an ADHD diagnosis in a donor or in a donor's first-degree relative, so a sibling, child, a parent, it says it should be considered case-by-case depending on things like severity. So ADHD, you know, it's so common.
According to the CDC, 15% of boys in the U.S. receive a diagnosis of ADHD at some point. So if we were just going to exclude based on a diagnosis of ADHD, there goes 15 out of 100 of our donor applicants before we even look at anything else. And those could be excellent donors.
So when I think about multifactorial conditions, I'm taking into account what is the incidence of this condition? Is it really common or is it rare? I'm taking into account severity. What does the medical management look like for the individual who's impacted? What was the age of onset? How many family members are impacted by this condition or genetically related conditions? And using all of that to make a determination. So it can be challenging, but a lot is going into it, certainly ASRM's guidelines, and then probably the expertise of a genetic counselor at that bank, hopefully, or maybe a physician at that bank to determine whether that condition might be an exclusion or an excluding factor or whether it might be considered acceptable.
How do you address concerns about donor family history accuracy? Are there any protocols in place at your bank to maximize accurate reporting and documentation of family history? And what about updates to reported family history over the years? Yes, those are such good questions and such valid concerns because family history, like you mentioned, it's inherently imperfect. It completely depends on what the donor's been told, what relatives have been comfortable sharing, and how they discuss health information in their family. So even with perfect intentions, a donor could be unaware of something.
And then the other piece is donor applicants might be 24 years old. And if a donor applicant has young parents, maybe their parents had them when they were 18 and young grandparents, some of those later onset conditions just haven't shown up yet because everyone in the family is young. So I always encourage people who are looking at donor family histories to understand they're not comparing apples to apples.
If you look at a 38-year-old sperm donor compared to a 22-year-old sperm donor, things might look pretty different just because of the age of the donor and their relatives. Now, that being said, there is no way that a GAMI bank can collect the medical records of every single provider that every donor family member has seen. It's just not possible.
So we do rely on donors to be honest and transparent with us. And we do stress the importance of that by explaining what this family history is for, what implications it has for future donor conceived people and their family members. And we go from that.
I think a lot of banks also have a system in place where there's multiple people going through this family history. So for example, at Seattle Sperm Bank, the donor fills out their family history online. Then they meet with a trained donor coordinator who's going to ask and fill in any gaps and ask for clarifications about things that might be missed like age of onset, severity.
Oh, what about these relatives? And clean it up. Then a genetic counselor is going to review it. The genetic counselor might have follow-up questions too.
And they're going to write an assessment of, okay, what does all of this mean in terms of chances for conditions for future children? And then finally, a doctor is going to review it when they meet with the donor in person for their physical exam and they may have additional questions. So there's multiple levels of review to try to make sure we're catching everything that's available to us. And then, yeah, you're right.
Updates are super important. Family history certainly is not static for any of us. So it's important that any GAMI bank has made their donors aware of the importance of updating them with new medical information for themselves or their close family members and has also informed all intended parents and recipients of donations that it's important they update the bank if their child receives a diagnosis because that then becomes part of the donor's family medical history.
So it can go both ways. It can be that the donor updates the bank themselves or a recipient updates the bank themselves. A future donor-conceived person updates the bank.
It can also occur when, for example, at Seattle Spring Break, we send out questionnaires to our donors regularly, our retired donors, to say, hey, have you had any changes in your medical history? What are they? And we ask them, give them some questions and some common conditions that often arise and take in that medical information. But that's only part of it. The next piece is what protocol does the bank have in place to investigate and report out those medical updates if they're relevant to everyone? So those are really great questions for people who are deciding how they want to go about finding their donor to ask a future bank or to ask a known donor, hey, what's the process going to look like if you receive a medical diagnosis? How can we get in touch with you if our child receives a medical diagnosis and we want to gather more information from you? Right, right.
Yeah, no, those are all kind of good questions to be thinking about for sure. I want to go a bit back to like those kind of multifactorial conditions that we talked about, right, where those that have those genetic and environmental influences. What are some of the biggest misconceptions that patients tend to have about genetic risks and the likelihood of those conditions being passed on through donation? I think I had to think about this one in advance, but I think what it is, it's something that maybe not everyone wants to hear, but it's the idea that a lot of people overestimate what family history and the genetic testing banks do, what that can predict, especially for multifactorial conditions.
Because these conditions also have environmental influences, we can't get at that, you know, with any of our screening we do at a gamete bank. So having a donor with no known family history and negative genetic screening, it doesn't guarantee that a child won't receive a diagnosis of something eventually. So I think in reality, the counseling that I noticed a lot of intended parents haven't received, and it really doesn't matter how they're conceiving, even just, you know, my neighbor next door who's attempting to conceive naturally, a lot of people just aren't aware that there's this baseline risk for so many conditions like birth defects, neurodevelopmental conditions like autism, cancer, all of these things.
It doesn't matter how you conceive, whether you use a donor or not, and no amount of screening can reduce those risks to zero. So that's kind of what I think the big misconception is. And the other one I will mention is, I think some people who work in assistive reproductive technology, as well as recipients of donors, sometimes assume that donors represent this paragon of health.
And in reality, you know, donors are just people like us. We all carry some genetic risk. Every individual is going to have some genetic variants, whether we can identify them or not.
Every individual is going to have susceptibilities for some conditions and maybe protective genetic factors for other conditions. When I was young and fresh in my career, and I worked at an ag bank associated with my clinic, I really used to view my role as like identifying the healthiest possible donors. And over time, my perspectives really shifted.
Now, what I see my role as is asking detailed and thoughtful questions, following up with our donors, following up with our recipients who have a donor-conceived child with the diagnosis, and being as transparent as possible, and explaining as clearly as possible what we know and what we don't know and what that means. Yeah, yeah. I definitely, so like I mentioned, I work on the clinic side, and I do work with patients using, you know, donor egg or sperm.
And, you know, many times I get the question, it's like, oh, which one would you pick, right? Which is the kind of like you were saying, like the healthiest donor. And I think it's almost impossible to pick that one donor. And I mean, kind of thing, like you were saying, you know, I see our job, you know, is to kind of walk patients through those conversation, or sorry, those decisions, I should say.
And I've definitely, you know, told patients, you know, I've had some patients who have a, you know, their mother died from suicide following depression. And so they definitely maybe want to avoid, you know, picking a donor with a family history of depression, maybe just because of their lived experience, even if the risk may not be as high, numerically, right. And then I've had donors care about very different things.
And I think that really kind of emphasizes what you're saying. We talked a bit about, you know, genetic carrier screening, can you tell me more about the role of that screening in, you know, sperm donor evaluation? So in other words, like, how are those results interpreted? And what would exclude a potential donor from eligibility based on those results? Yeah, absolutely. So, again, most carrier screening panels include hundreds of diseases these days, you know, a lot of labs are now offering carrier screening panels that include 800-900 different genes and genetic conditions, right.
So when we test for that much, the vast majority of people are going to come back a carrier of at least one condition. And most of the time when you're a carrier, meaning we've got two copies of each of our genes, one of your two copies has a misspelling or a mutation, a variant. When you're a carrier, usually that second copy of the gene makes up for your broken or mutated copy.
And you don't experience any symptoms or any differences due to being a carrier. But as we learn more, and as more people complete carrier screening, we're identifying that a portion of genetic conditions we screen for, carriers actually can have symptoms related to the full-blown condition. It can have milder symptoms, and there can be a health impact due to these.
So carrier screening results are getting a little messy, I would say now. They can be a bit of a can of worms because we can no longer say, oh, you're a carrier, you're healthy, that's fine. It depends on the condition.
It depends on the variant. So having a genetic counselor involved in reviewing carrier screening for a donor, or should I say an egg source and a sperm source matching together is really important now as the screening has evolved to become quite a bit more complicated than 10 years ago. So when we look at a carrier screening result, most of the time we can say, okay, this donor applicant is positive for a few conditions, they're carriers, we don't expect them to have any symptoms.
We can still accept them as a donor, but we want recipients who are looking at this donor to be aware and for them to do carrier screening if they think that could help give them additional information and determine whether there's an increased or decreased risk for some of these conditions. Alternatively, sometimes a donor is excluded. Sometimes we surprisingly find a donor who's affected with a condition that can look severe and maybe they haven't manifested symptoms yet.
Sometimes, for example, in egg donors or sperm donors, sometimes we see an X-linked condition, a condition where the gene that's impacted travels on the X chromosome and there could be a high chance that offspring or children of that donor could be impacted with the condition. So really the goal of carrier screening is not to eliminate genetic risk, that is impossible, but it's to identify what we can reduce the likelihood of some of these more serious, well-described recessive diseases that can be anticipated and that we can address. So that's what I always try to emphasize to individuals looking for a donor is we are not able to eliminate genetic risk at all.
We are just looking for what we know and what we can test for at this point in time. Yeah, no, absolutely, that's a very good reminder. I definitely have had patients, you know, come to me and be like, yeah, I just am browsing these donors online and I just can't seem to find one that's not a carrier of a genetic condition.
And I have to backtrack a bit with them and be like, I mean, I don't know, that's going to be a very hard task to do when you're screening these donors for like 500 conditions and more. And so it's kind of reminding them like what you were saying, which is, you know, it's not about eliminating genetic risk, it's just about being informed of those risks and kind of taking those next steps in order to reduce that risk being passed on. So I think my last question for this podcast will be about any recommendations that you would give recipients or clients when selecting their donor based on their genetic and family history.
And I know we, you know, maybe touched on it a bit, but do you have any kind of final thoughts or recommendations as we wrap up? Definitely. I think my main recommendation to someone who would be like starting their search and diving into genetic results and family history results on donor profiles is to focus on understanding risk rather than trying to eliminate it. And I think we've kind of been saying this throughout our conversation, every donor and every person has some degree of genetic risk or susceptibility to certain conditions.
So you have to accept that. And most people who practice in medicine, you know, like for me during my pregnancies, I'm always thinking, oh gosh, like during my next prenatal screen, maybe they could see some, there could be something there. We're aware of that baseline risk, but sometimes if you haven't practiced the medicine and it's a first pregnancy and you're just getting comfortable with the idea of having a child, you don't think about that yet.
And you're not aware of that. So you have to accept anybody who's having a child, no matter how they're attempting to have that, bring that child into the world, there is this baseline risk and we can't eliminate it. There is no way to do so.
So let's focus on what we know about donors and about ourselves, our own family history and genetic carrier screening, our potential donors, family history and carrier screening, and understand it and try and make the best decision with the information we have today, knowing that that information is going to grow and change in the future for our own family history and our donors. So it's kind of about looking at these family histories as tools. They're imperfect tools though, right? And I think going along with that, it's really helpful if taking a step back before you even get into the family history and the genetic test results to reflect on your own values and your own hopes for a donor.
What are the most important criteria for me in looking for a donor? Is it a known donor? Is it a donor that I can connect with before my child is 18? Or is that not one of the most important pieces? Is it like you said, maybe I have a really significant psychiatric history personally and in my family tree, and I really want to look for a donor that doesn't have that type of history to kind of reduce the genetic load of psychiatric conditions or same thing goes with cancer. So thinking about it and maybe speaking with a genetic counselor to try and rank what your values are ahead of time before you get into the weeds of looking at all these very lengthy family histories and genetic profiles. So you can try and kind of go in with a plan of what you're looking for.
Yeah. Thank you. I love that.
Yeah. Any final thoughts Katie that you have? Yeah. I think there was one other thing I wanted to mention.
That's kind of a hot topic in the donor world right now. And that is medical diagnoses in children of donors. And we're hearing stories in the news and social media about kids who've been conceived using a donor who receive a diagnosis that's unexpected and the follow-up for that.
So I think an important question to ask when you are looking at a gamete bank or looking at a different donor arrangement is kind of how will that situation be handled? What will you do in that situation? And to be aware that, for example, at Seattle Sperm Bank, one of my primary jobs is looking into diagnoses that children of donors receive and investigating them, determining what that might mean for other donor conceived children from the same donor and sending out medical update letters, sending out letters to inform parents of that new diagnosis. And that's something that there's not much detail about at all in ASRM's guidelines about how family history should be handled. So that's an important question for a bank to understand how would that information come to me? What do you do when you receive that information at your gamete bank? And just know that there are a lot of banks that are trying to get this right.
And there's a lot of genetic counselors working at gamete banks that handle this information. So it kind of just all depends on internal protocols, honestly. So that's a good question to ask is how would this information come to me? If there were updates in the future? Yeah, for sure.
Okay, well, thank you so much, Katie, for being here. I really enjoyed every bit of our conversation and learned some even. And thank you for our listeners for tuning in.
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.
