Divergence Between Clinician and Patient Perspectives on Polygenic Embryo Screening: A Qualitative Study

Abstract

Objective:

To explore and compare the perspectives of clinicians and patients on polygenic embryo screening.

Design:

Qualitative.

Subjects:

Fifty-three participants: 27 reproductive endocrinology and infertility specialists and 26 patients currently undergoing in vitro fertilization or had done so within the last five years.

Main Outcome Measures:

Qualitative thematic analysis of interview transcripts.

Results:

Both clinicians and patients often held favorable views of screening embryos for physical or psychiatric conditions, though clinicians tended to temper their positive attitudes with specific caveats. Clinicians also expressed negative views about screening embryos for traits more often than patients, who generally held more positive views. Most clinicians were either unwilling to discuss or offer polygenic embryo screening to patients or were willing to do so only under certain circumstances, while many patients expressed interest in polygenic embryo screening. Both sets of stakeholders envisioned multiple potential benefits or uses of polygenic embryo screening; the most common included selection and/or prioritization of embryos, receipt of more information about embryos, and preparation for the birth of a predisposed or “affected” child. Both sets of stakeholders also raised multiple potential, interrelated concerns about polygenic embryo screening. The most common concerns among both sets of stakeholders included the potential for different types of “biases” – most often in relation to selection of embryos with preferred genetic chances of traits –, the probabilistic nature of polygenic embryo screening that can complicate patient counseling and/or lead to excessive cycles of in vitro fertilization, and a lack of data from long-term prospective studies supporting the clinical use of polygenic embryo screening.

Conclusion:

Despite patients’ interest in polygenic embryo screening, clinicians feel such screening is premature for clinical application. Though now embryos can be screened for their genetic chances of developing polygenic conditions and traits, many clinicians and patients maintain different attitudes depending on what is specifically screened, despite the blurry distinction between conditions and traits. Considerations raised by these stakeholders may help guide professional societies as they consider developing guidelines to navigate the uncertain terrain of polygenic embryo screening, which is already commercially available.

Capsule:

Clinician and patient perspectives on polygenic embryo screening both diverge and overlap, inviting greater reflection on concepts of condition severity and health for the development of professional guidelines.

INTRODUCTION

Polygenic embryo screening (PES), also known as preimplantation genetic testing for polygenic diseases (PGT-P), differs from preimplantation genetic testing for aneuploidies (PGT-A) or monogenic conditions (PGT-M) in meaningful ways.¹ Compared to PGT-A and PGT-M, PES has the capacity to screen for physical and psychiatric health conditions (e.g., diabetes, depression) as well as physical and cognitive traits (e.g., height, intelligence) (1). However, PES relies on inherently probabilistic polygenic risk scores, which are not yet standardized (2) and have limited portability to individuals of non-European ancestry (3). Further, PES may have limited utility in selection for traits (4), while the potential utility for reducing risk of disease is more complex (5–7). Nevertheless, PES has the potential to significantly alter the clinical experience of patients undergoing in vitro fertilization (IVF), and to expand IVF to populations that do not have fertility issues (8).

PES is currently available in the U.S. and other countries that do not regulate what kind of genetic testing may be conducted on embryos (9). Though a few professional organizations currently oppose the use of PES (10–13), uptake of PES will be determined largely by how clinicians, IVF patients, and the public view its potential utility, costs, and harms – at both individual and societal levels. To understand the potential future trajectory of PES, elaborate on the full range of considerations, both for and against the use of PES, and inform relevant guidelines that may be developed by professional societies, this qualitative study is the first to investigate the perspectives of US-based reproductive endocrinology and infertility specialists (REIs) and IVF patients regarding this new type of embryo screening.

METHODS

We conducted semi-structured individual interviews over internet-secured video calls lasting between 29 and 86 minutes, with an average of 52 minutes for clinicians and 54 minutes for patients, which were audio-recorded and professionally transcribed.

Our multidisciplinary team (bioethicists, social scientists, and statistical geneticists) developed interview guides based on a literature review of PES, including its utility and ethical concerns. Interview questions investigated interest in, potential uses, and concerns about PES (Appendices 1 and 2). We piloted the interview guides with two clinicians and two patients and no substantive changes were necessary. Interviews included an explanation of PES with visualizations of mock embryo reports based on published examples from a commercial lab (14). Participants self-reported demographic information.

This study was approved by the Baylor College of Medicine Institutional Review Board (IRB), protocol H-49262 with a waiver of written documentation of consent. All participants provided verbal consent and received a $50 gift card.

Recruitment

Between January and December 2022, we recruited clinicians and patients via convenience, random, and snowball sampling until we assessed that we reached “saturation” – the point at which subsequent data collection no longer generated novel insights (15).

Clinician participants were U.S.-based practicing REIs. For convenience sampling, we invited clinicians known to the research team. For random sampling, we conducted a search of U.S.-based members of the Society for Reproductive Endocrinology and Infertility (SREI) [https://www.socrei.org/sectiondirectory] which resulted in a list of 776 individuals. We used a random number generator to target 250 clinicians and made up to three attempts to invite them to participate.

Patient participants had to be currently undergoing IVF or had done so within the last 5 years. As part of convenience sampling, we invited IVF patients known to the research team. To obtain a random sample of IVF patients, we collated a list of 453 fertility clinics across the U.S. from a public fertility services webpage, which is no longer active [https://cofertility.com/get-to-know-us/], and invited them to post a flyer in their clinics. These flyers gave interested patients instructions for contacting the study team. Five fertility clinics posted the flyer (two each in the West and South, and one in the Midwest).

Analysis

Using thematic analysis (16), we developed a codebook based on deductive themes driven by the interview questions and unanticipated themes generated inductively from the interview data. Using Dedoose, a qualitative analysis program, at least two team members independently coded each transcript. Subsequently, one team member abstracted subthemes from coded excerpts, with a second team member reviewing the abstractions to confirm or discuss and reconcile subthemes (17). Because concerns were numerous and clustered, we grouped them thematically according to a third level of abstraction (17). Finally, for each code, one team member developed a memo, highlighting key subthemes and exemplary quotes, and a second team member reviewed for accuracy and comprehensiveness.

RESULTS

See Figure 1 for recruitment details. In total, 27 of 235 invited REIs agreed to be interviewed, resulting in an enrollment rate of 11%. Because of our passive approach (i.e., clinic flyers) for patient recruitment, we are unable to report an enrollment rate for patients.

Figure 1:

Recruitment Flow Chart

Theoretical saturation was reached by interviewing 27 clinicians and 26 patients. Our sample of mostly White or European-American clinicians were situated across all U.S. regions, working in various practice types, and had a range of 3—40 years of REI experience, with a mean of 21.4 years. Patients were well-educated and wealthy, and most self-identified as female and White or European-American. Some had used or were planning to use preimplantation genetic testing. (For additional demographic details, see Tables 1 and 2.) Exemplary quotes and frequencies of subthemes are reported in Table 3.

Table 1:

Clinician Demographics

Demographics		Counts	% of N=27
Gender	Female	12	44.4%
	Male	15	55.6%
Hispanic/Latino	Yes	1	3.7%
	No	26	96.3%
Race*	American Indian, Native American, or Alaska Native	0	0.0%
	Asian	5	18.5%
	Black or African American	0	0.0%
	Native Hawaiian or Pacific Islander	0	0.0%
	White or European American	20	74.1%
	Other	6	22.2%
Region	Northeast	6	22.2%
	Midwest	6	22.2%
	South	9	33.3%
	West	5	18.5%
	Other	1	3.7%
Current Type of Practice	Academic	8	29.6%
	Military	1	3.7%
	Privademic	5	18.5%
	Private	13	48.1%

^*Respondents could report more than one category

Table 2:

Patient Demographics

Demographics		Counts	% of N=26
Gender	Female	24	92.3%
	Male	2	7.7%
Hispanic/Latino	Yes	4	15.4%
	No	22	84.6%
Race*	American Indian, Native American, or Alaska Native	0	0.0%
	Asian	7	26.9%
	Black or African American	0	0.0%
	Native Hawaiian or Pacific Islander	0	0.0%
	White or European American	18	69.2%
	Other	7	26.9%
Region	Northeast	3	11.5%
	Midwest	3	11.5%
	South	6	23.1%
	West	14	53.8%
	Other	0	0.0%
Highest Level of Education	Associate’s degree	2	7.7%
	Bachelor’s degree	5	19.2%
	Professional degree (JD)	2	7.7%
	Master’s degree	14	53.8%
	Doctorate degree	3	11.5%
Annual Household Income Before Taxes	$75,000—$99,999	3	11.5%
	$100,000—$149,999	7	26.9%
	$150,000 or more	16	61.5%
Number of IVF Attempts	1	14	53.8%
	2	11	42.3%
	3 or more	1	3.8%
Current Number of Children	0	15	57.7%
	1	5	19.2%
	2 or more	6	23.1%
Completed Family Planning	Yes	4	15.4%
	No	22	84.6%

^*Respondents could report more than one category

Table 3:

Exemplary Quotes

Theme	Subtheme	Frequencies	Exemplary Quote
Attitudes About Screening Embryos for Conditions	Positive	C: 3/27; 11%	“Yeah. I would be open to [screening embryos for psychiatric conditions, like depression and schizophrenia], primarily because the medical knowledge I know is that medications aren’t as helpful for those traits. And so they’re treatable, but not really to the degree.” (C18)
		P Self: 7/26; 27%	“I mean, this is great information to know. If you could tell that you have a higher pre-dispensity [sic] to have these conditions, I think it definitely makes it easier as a parent. [...] For knowledge and for health cares, yeah. I definitely want to know those things.” (P5)
		P Others: 21/26; 81%	“I think everybody’s entitled to screen for any conditions that they’re interested in.” (P7)
	Conditional	C: 16/27; 59%	“But if there are specific genes or clusters of genes that are highly predictive of a severe, life-threatening disease like breast cancer or other cancers, or families of cancers, I think that that would be reasonable [to screen for in embryos].” (C14)
		P Self: 17/26; 65%	“Oh, I suppose [I would] probably like [to screen my embryos for] the big conditions that are really impactful on somebody’s quality of life. So I’m thinking things like MS, MD, cancer.” (P18)
		P Others: 4/26; 15%	“[...] I could see why people maybe would want this [information]. It maybe wouldn’t determine if you transferred them, but maybe it could determine diet and what you would do, especially with a cancer probability or things like that [...]” (P21)
	Ambivalent	C: 8/27; 30%	“I think there are certain people who’ve been so impacted by [psychiatric conditions], and this is something I’ve had patients, like autism and schizophrenia or severe mental health disorders are two things that I’ve had patients ask me more about because I think it’s really affected their... Whether it was a close family member or friend that they saw suffer, and they really want to avoid that. But then it’s a fine line because where does it become discriminatory almost?” (C17)
		P Self: 1/26; 4%	“I feel happy with the level of information we got out of the chromosomal normality/abnormality review. I don’t think I would want to know ... I mean, I’m thinking like poor eyesight, poor hearing, things like that, [I’m] not so interested [in screening for in my embryos]. More like significant, lifelong potential problems that would be based, I would think, largely in genetics [I would be interested in screening for in my embryos].” (P7)
		P Others: 1/26; 4%	“So part of why I don’t trust it for me and for people in general is I think people do a really bad job at estimating risk and understanding risk. And so that’s why I’d be skeptical of letting people make decisions based on this.” (P26)
	Negative	P Self: 1/26; 4%	“[...] I think the environment can also really affect the mental health piece. I think, though you can be predisposed, or you can have certain susceptibilities to mental health, there’s a lot that can happen in your environment that can help you. You can live and you can thrive, not just live, but thrive, even with mental health, with that going on.” (P21)
Attitudes About Screening Embryos for Traits	Positive	P Others: 10/26; 38%	“We all have different things that we would want to know or don’t know. So, if all the choices are there, it’s going to be each person’s personal preference, what they want to do. And for us, it’s fine. Yeah, having just the option open for me, obviously, would be ideal. I would screen for whatever’s available.” (P20)
	Conditional	C: 8/27; 30%	“Maybe the only way I could see [screening embryos for polygenic traits] is someone using donor gametes, and maybe they want... Usually, they’ll select a donor who has characteristics similar to them for that exact reason. So maybe in that situation I could see, ‘All right. If this one’s going to potentially look more like me, maybe use it in that way.’” (C17)
		P Self: 7/26; 27%	“[...]if it’s something that’s already in a screening that I’m getting anyway, then sure. Why not?” (P11)
		P Others: 4/26; 15%	“I think if you have the technology, the money, the everything in your hand, you can [screen embryos for traits].” (P6)
	Ambivalent	C: 10/27; 37%	“But the question is that, if screening for these polygenic traits are available, and the patients know that they’re available, and come to me specifically asking to have these polygenic traits screened for, I think... I struggle with that. Being pro-choice, I would probably allow them to do that, because it is their choice, it is their children. And even though I may be uncomfortable with it, I’m not sure that I’m in a position to impose my ethical beliefs and personal beliefs on my patients.” (C14)
		P Self: 8/26; 31%	“Yeah, so I’m not opposed to screening for height, hair color, eyes, whatever. I’m not opposed to that. It’s just not something that I would consider a priority for me.” (P16)
		P Others: 7/26; 27%	“[...] I can’t think of an experience of why people would want to [screen embryos for traits]. But I guess maybe people would. I don’t know.” (P21)
	Negative	C: 9/27; 33%	“I don’t think [screening embryos for physical traits like height or hair color is] really what I want to be doing as a medical professional in reproductive endocrinology, and it doesn’t really have a role.” (C3)
		P Self: 11/26; 42%	“I wouldn’t [screen embryos for any traits]. To me I don’t really need to know about those kinds of things. In fact, I like the idea of kind of discovering your child once they’re born. Like, what are they going to be like and what traits do they have?” (P18)
		P Others: 5/26; 19%	“I would say, the [traits] that you suggested, the height, hair color, intelligence. I don’t think, people need to know that. I just don’t see it as being relative to the overall goal, which is having a child that is free of certain genetic conditions.” (P11)
Blurred Boundaries Between Conditions and Traits	Physical	C: 7/27; 26%	“We think about some diseases like, well, not the diseases related to traits, but some patients may be very sensitive to height, some are not. Like I’ve had patients that have come in and they’re deaf and they want a deaf child. Or they come in and they have dwarfism and they like a shorter person. Whereas others are very sensitive to it and say, well, they don’t want that.” (C27)
		P: 7/26; 27%	“[I would screen my embryos for o]besity. There’s no obesity in my family, but again, because I already know it’s not going to be my egg, but if that was a situation, obesity would be one of them. Of course, anything that has to do with the body weight, I want to make sure that there is no predisposed gene that is going to lead to heart disease, but also obesity or any other condition that might affect the, yeah, just the wellbeing of this individual, this baby, future human being.” (P10)
	Cognitive	C: 2/27; 7%	“Unless there was some genetic reason to suspect for, for example, like achondroplasia or something, I would prefer not to check [embryos] for height, and certainly not color of eyes and hair. Intellectual ability maybe a little bit because I don’t know how you separate things like autism on a spectrum, Asperger’s, et cetera. So intellectual ability maybe, but the others I have a hard time.” (C24)
		P: 7/26; 27%	I guess if there was a good way to measure intelligence [I would screen for that in my embryos]. I don’t know if IQ is the best one, but just in terms of... Because you can have someone who’s not book smart, but street smart and has a lot of ingenuity. [...] And I guess that, it’s related to screening for Down’s syndrome. Screening for the developmental learning disabilities, kind of stuff. Whatever is the metric for that, screening for that.” (P15)
Clinician Willingness to Discuss or Offer PES	Unwilling	C: 10/27; 37%	“If you’re testing [polygenic conditions at the] embryonic stage, obviously, that has not been done to then follow out through a lifetime to see how it actually plays out. I guess I’m just not as convinced that these polygenic scores are that accurate.” (C2)
	Conditional	C: 14/27; 52%	“If they asked me about [PES]? Sure[, I’d tell patients about the availability of it]. But I don’t think this is something I’d bring up.” (C4)
	Willing	C: 3/27; 11%	“Some patients may have family members, for example, that have significant risk of things, like type one diabetes, but there’s no real screen for that, and they may have, for example, a high fear of that or something like schizophrenia, for example. I think they’re one of the things that patients might want to screen for.” (C26)
Patient Interest in PES	Interested	P: 15/26; 58%	“For [me and my husband], personally, we’re grateful that the information is there and an option to be used.” (P20)
	Conditional	P: 4/26; 15%	“I think if it’s not crazy expensive and it doesn’t hurt the embryo any more than just the regular biopsy or the biopsy I already did, then I think it’s fine to get this information.” (P14)
	Ambivalent	P: 5/26; 19%	“There’s days that I debate with myself with whether or not I’d want a test to see if the little girl would have endometriosis, because it is so painful and I wouldn’t want her to go through that, but then I’m also like, by the time [I] think she’s an adult, maybe we’ll actually have a treatment that’s okay. I’m like, I don’t want to necessarily make decisions like that, but also it’s yeah. It’s one of those ones I go back and forth on for that specifically, but then like other ones, if there’s a for sure chance that the kid is going to be severely, mentally handicapped and they won’t have necessarily a good quality of life, then I potentially want to see if there’s a way that we can see that. Otherwise, probably not just because what are you going to do? What are you going to do with that knowledge?” (P3)
	Not interested	P: 2/26; 8%	“So then, it’s like to me, this is way too much information and way too complicated that I would probably end up just going with the best chance that this embryo is going to turn into a child and go with that one.” (P22)
Potential Uses	Selection	C: 7/27; 26%	“I think that it’s maybe more understandable that someone would want to have this if they have a family history, right? I think of a couple who had a rich family history of cancer, they’ve had cancer genetic panels and it hasn’t revealed anything. Okay, so there’s not a smoking gun that we can look for with PGT-M, for instance. But they still have a strong motivation to avoid what they’ve seen so many family members go through. I think that’s understandable, that that might attract some people towards this technology.” (C21)
		P: 21/26; 81%	“I would only choose the embryos that came back genetically normal to transfer, and then have the other ones discarded.” (P12)
	Prioritization	C: 1/27; 4%	“[PES] would probably influence embryo transfer order.” (C4)
		P: 7/26; 27%	“The [embryos] that were perfectly fine, we’re going to try first. The ones that were a little iffy, we’d try next. And then the ones that had abnormalities, we wouldn’t even try.” (P14)
	More Information	C: 4/27; 15%	“I think [interest in PES will be] very dependent on the patient. I think some patients want more information.” (C1)
		P: 18/26; 69%	“[PES is] just some added information in terms of what is already a very controversial thing of just doing IVF in itself, or even any kind of assisted reproductive therapy treatment.” (P15)
	Preparation	C: 5/27; 19%	“[...] I think this is very useful information. [... C]an they then take proactive steps to minimize the risk with lifestyle changes and controlling their nutrition and exercise and whatever?” (C24)
		P: 15/26; 58%	“[...] you need to know if you need to save up for college for a kid or not, or if you need to know, hey, we need to brace ourself. And does intelligence include maybe being on the autism spectrum and things that. I know that there’s no genetic testing for autism, but I’m going to say, so you can know, you can prepare yourself better as a parent that, hey, we might need early intervention. We might need additional resources to put this child through special education. Just to know and prepare yourself financially and emotionally just say, hey, we might need these extra resources. We might need them to help the kid.” (P5)
	Informed Decision-Making	P: 10/26; 38%	“I just like to know as much information as possible, so I can make educated choices about a potential child that I would be raising.” (P12)
	Reassurance	C: 1/27; 4%	“But I think that [PES] could be a really useful tool for patients, and especially if they have a family history or something that they’re personally worried about, or that want to have a healthy baby is a really pervasive thought. It could give them another level of reassurance that the embryo that we transfer is going to have a good outcome. I think it could be really good.” (C3)
		P: 3/26; 12%	“[...] I want to make sure that there is no predisposed gene that is going to lead to heart disease, but also obesity or any other condition that might affect the, yeah, just the wellbeing of this individual, this baby, future human being.” (P10)
	Curiosity	P: 4/26; 15%	“I think that would just be really neat to know if [future children are] prone to certain cancer or genetic mutations, because I found out that I had a genetic mutation that causes blood clotting. So that would be neat to know if my embryos had that too.” (P1)
	Scientific Advancement	C: 2/27; 7%	“I think it’s important from a scientific perspective to push our understanding of science forward. And in some ways, from a research perspective, this becomes important and interesting. And the research enterprise isn’t lost on me.” (C13)
Potential Concerns About Social Harms	Biases	C: 18/27; 67%	“[... I]t’s tested only a certain population when you’re showing these average risks, that’s for the general population, not for this patient’s ethnicity and all. So it’s kind of not apples to apples.” (C23)
		P: 14/26; 54%	“I guess my only concern [about screening for traits] would be that it would be superficial things would affect the way that I transfer the embryo because then, I’m just being maybe superficial or these things aren’t like super [important ...] (P8)
	Loss of Perspective	C: 9/27; 33%	“I don’t think that [screening embryos is] appropriate to do for just height and hair color because those features don’t have any direct implications for health.” (C14)
		P: 12/26; 46%	“I just feel like, as humans, this is too much information for us. The baby is viable. The baby can make it to live birth. What more do you need to know, other than that?” (P21)
	Economic Aspects	C: 11/27; 41%	“This is all profit-driven. It’s not driven by any kind of science or good medicine or anything else.” (C22)
		P: 10/26; 38%	“So I would worry just about the gap in who could get help but or not, and what kind of help they would get in making these decisions, or even getting the screen. And then just seeing people with the financial means to be able to choose beautiful, intelligent children. And then continuing that divide.” (P19)
	Affecting Parent-Child Relationship	C: 5/27; 19%	“[...] I think that’s just dangerous to tell people what’s going to happen in the future when often it won’t happen, no matter how accurate it is. And then they’re going to be disappointed as parents or just have challenges already with their kids.” (C7)
		P: 5/26; 19%	“Oh, I guess the concern [over screening embryos for health conditions] would be, like if I did end up having a baby that I did screen and I knew that there was a potential for them to have some sort of disease, well, it’d be a lifetime of worry for that child. And then, do I tell them or not ...” (P12)
	Consumerist Aspects	C: 7/27; 26%	“I’m not doing designer baby. This shouldn’t be Gattaca, you shouldn’t be able to check your boxes and I’ll screen that and find it. Not interested. When we start doing that, I’m probably ... If that became widespread, I probably wouldn’t practice [medicine].” (C13)
		P: 1/26; 4%	“[Screening embryos for traits] feels like shopping.” (P19)
	Enhancement	P: 4/26; 15%	“I don’t know, maybe we would end like that where we only had superior people.” (P15)
Potential Concerns About Individual Harms	Harm to IVF Patient	C: 13/27; 48%	“Then, there’s going to be the person who’s just like, \Well, I want as perfect of a child as possible. Can we do all these things?’ And those patients often are unrealistic because they’re not infertile and don’t ... It’s hard. Am I putting them more at risk by putting them through this?” (C17)
		P: 10/26; 38%	“I mean, my only really true concern is that for me, [screening for health conditions is] going to result in not moving forward with a pregnancy. Because I’ve already had two [embryos] that like, well, nope, you can’t use those. Sometimes I wonder, well maybe it would’ve been best just to not have even known. But I mean, that’s just more a personal disappointment.” (P18)
	Limiting Embryos	C: 11/27; 41%	“I think one [of my concerns with screening for polygenic conditions] is not having any embryos to use at the end of the day. But more importantly, I always tell my patients, if you get that information, you have to think about, are you going to use it or not? And if you’re going to use that information, are you comfortable knowing that you’re using embryos that might have these conditions? Versus, not knowing. If you don’t know, you can’t say you intentionally did it. But if you know the information, now you have to decide if it’s something you’re comfortable replacing.” (C10)
		P: 6/26; 23%	“For myself, I just, I feel like there’s so much you could diagnose and if you diagnose everything, you’re not going to end up with [an] embryo that you want because you’re just going to find something wrong with every, every one. So I know that I don’t want to restrict myself from having a family because we can identify it, because we can identify everything.” (P19)
Potential Concerns About Clinical Aspects	Uncertainty/Probability	C: 16/27; 59%	“[... W]e don’t know if that embryo that scores high will have a severe case, a mild case, a treatable case. We don’t know. I don’t know how I would counsel a patient effectively for that.” (C11)
		P: 10/26; 38%	“I guess there’s nothing that’s guaranteed in life, I guess, so even in genetic testing. But [...] the possibility of incorrectly identifying that this embryo has this particular disease and then now you’re like, ‘Okay, now this one’s... Scrap this one.’ I don’t know, just I guess that’s the concern. Especially when there’s not... It doesn’t seem like you get many to start even with each of these cycles, and all the work and stuff you have to go through to get just one or two.” (P23)
	Lack of Data	C: 20/27; 74%	“If you’re testing it embryonic stage, obviously, that has not been done to then follow out through a lifetime to see how it actually plays out. I guess I’m just not as convinced that these polygenic scores are that accurate.” (C2)
		P: 5/26; 19%	“Mostly my concerns would be on accuracy because I read a lot of scientific papers, I know that [screening embryos for health conditions is] based on the best science available [at the time...]” (P24)
	Complexity Challenges Utility of Selection	C: 12/27; 44%	“There’s one more thing that [polygenic scores] do not evaluate at all, and that’s the epigenetic component, meaning the environment, how it can affect ... And that is not even ... It’s not even discussed in any of these conversations that, yeah, these are the risks, but these could be modifiable risks for some of these things, even in polygenic disorder, depending on the epigenetic marks that are placed, which in turn, may depend on environmental exposures.” (C5)
		P: 4/26; 15%	“[... D]epression, that would be a hard one [for me to screen in embryos] because so many people deal with it and there’s so many environmental factors too, but I don’t know how much that would help me.” (P19)
	Harm to Embryo	C: 1/27; 4%	“I would not let [my patients] do that test or advise them not to do it, if [PES] presented an additional risk [to the embryo].” (C19)
		P: 8/26; 31%	“Yeah, obviously, [my concern about screening embryos for health conditions is] if it’s going to take a toll on the embryo after it has been cryo-frozen and unfrozen, and just going through the whole process.” (P20)
Potential Concerns About Values and Virtues	Embryo Discard	C: 13/27; 48%	“We could be tossing away normal embryos.” (C27)
		P: 6/26; 23%	“[...] I guess if I had a concern [about screening embryos for traits], it would be that people would undergo multiple egg retrievals and create all these embryos and then not use them.” (P1)
	Lack of Humility	C: 3/27; 11%	“I don’t think it’s okay for people to come to believe that they can control everything in their lives. I think that’s kind of an adolescent view. Some things are hard, but that’s life. And I’m not eager to change that formula, that you can’t control everything.” (C6)
		P: 8/26; 31%	“I think [screening embryos for traits is] kind of scary in some ways, because then you’re leaving out some of the chance, some of the probability, some of the unknown.” (P17)
Potential Concerns About Governance	Difficulty Setting Limits	C: 12/27; 44%	“I think it would be very reasonable, although perhaps against what most of American IVF has looked like, to make anything that’s more trait-based off limits, and to have that be something that’s just not available. [...] People would still find ways to pursue it. They’d send it to a country that wouldn’t have such restrictions for their analysis, and this could still happen, but it’s reasonable to make that a harder thing to do instead of an easier thing to do, so it doesn’t become, getting back to that primary concern I had, such an incentive to pursue IVF for couples who otherwise would not need or benefit from it.” (C21)
		P: 4/26; 15%	“I don’t know how this would work, but I almost feel like there should be some certain criteria as to why we’re doing this. Is it some family history that you’re looking at, the schizophrenia? Do you have schizophrenia in your family history, and that’s why you’re looking at it? But then someone could not have family with schizophrenia. They just experienced someone with schizophrenia, and they’re like, ‘I want to know if my child is predisposed to schizophrenia,’ I guess.” (P21)
	Beyond Physician’s Role	C: 5/27; 19%	“And I think traits is very different from disease. [...] And I would actually be worried if somebody was prioritizing traits over health, because I think as doctors we’re in the business of improving health by itself.” (C16)
	Liability	C: 3/27; 11%	“I mean, inevitably, how many lawsuits are going to happen because you’ve supposedly chose an embryo that’s going to be tall, beautiful, and smart, and they’re short, squat, thick, and a little dull. Are the parents going to sue the companies, the IVF facilities because their child didn’t meet their expectations?” (C20)
		P: 1/26; 4%	“And then, is there a disclaimer in your agreement that says if the baby doesn’t turn out exactly how you expected or how you chose, you won’t come back and sue us because we thought we had the right genes?” (P24)

Note: “C” refers to clinician frequencies; “P” refers to patient frequencies; “Self” refers to patients’ discussion of personally screening embryos for conditions/traits; and “Others” refers to patients’ discussion of others screening embryos for conditions/traits.

Attitudes about screening for conditions and/or traits

Clinicians and patients often held positive attitudes about screening embryos for physical and psychiatric conditions. However, clinicians tended to temper their positive attitudes with specific caveats, such as limiting embryo screening to conditions that are in one’s family history and/or considered severe. A minority of clinicians and patients opposed or felt ambivalent about screening for various conditions because of their variable severity, most often discussed with respect to psychiatric conditions (e.g., depression), or concern over how such information would be applied (e.g., discomfort with using it for selection). (For attitudes about specific conditions, see Figure 2.)

Figure 2:

Attitudes on Screening Embryos for Most Discussed Conditions

*not polygenic

In contrast, screening embryos for traits generated greater variation of opinion. Clinicians expressed negative views about screening for traits more often than patients, who generally held more positive views. A minority of both sets of stakeholders were ambivalent about various traits. Intelligence was the most contentious trait; most clinicians that mentioned intelligence were against such screening, whereas most patients that mentioned it favored its screening. Opposition to screening embryos for traits was largely due to the belief that it is trivial, irrelevant to health or well-being, and/or beyond the role of medical professionals, as well as discomfort with using such information for embryo selection. Reasons for favoring screening for traits were largely based on respect for patients’ reproductive autonomy, even when some patients reported they were not interested in doing so themselves. (For attitudes about specific traits, see Figure 3.)

Figure 3:

Attitudes on Screening Embryos for Most Discussed Traits

*not polygenic

Some clinicians and patients’ responses, however, suggested that the distinction between conditions and traits can be blurry. They occasionally mentioned obesity or achondroplasia when discussing screening for physical traits, and autism, Down syndrome, or learning disabilities when discussing screening for intelligence.

Clinician reluctance to offer or discuss PES

Most clinicians were either unwilling to discuss or offer PES at this time or were willing to do so only under certain circumstances, most often if the topic was patient-initiated or PES was part of a research study. Some clinicians were willing to discuss or offer PES depending on the patient (e.g., those who, from the clinician’s perspective, were statistically savvy or had a compelling personal or family history of a polygenic condition), characteristics of the condition (e.g., untreatable), or external circumstances (e.g., more time for counseling; regulatory approval). Only a few clinicians were unconditionally willing to offer or discuss PES with patients at this time.

Patient interest in PES

Despite clinicians’ hesitancy to offer or discuss PES, all 27 thought that at least some patients would be interested in such screening. Indeed, many patients expressed interest in PES during interviews. A few patients were interested in PES depending on various factors, such as financial costs or family history. Additionally, several patients maintained mixed feelings of interest (particularly for conditions they perceived as serious), tempered with multiple concerns (e.g., negative effects on parenting, potential for information overload, and boundaries around acceptable uses of PES). Two patients indicated they had no interest in PES, feeling it was too much information or irrelevant for their embryo selection.

Potential uses of PES information

Though many clinicians perceived PES as potentially beneficial or useful for patients, some clinicians did not mention any potential benefits or uses of PES or said it was not beneficial or useful. In contrast, all 26 patients perceived PES as potentially beneficial or useful for themselves and/or other patients.

Clinicians and patients who envisioned potential benefits of PES often mentioned multiple uses, including selection and/or prioritization of certain embryos; receipt of more information about one’s embryo(s); preparation for the birth of a predisposed or “affected” child; informed reproductive decision-making (i.e., using PES information to select embryos versus prepare for the birth of a certain child); reassurance of an embryo(s)’ lack of predisposition to certain conditions; satisfaction of curiosity; and scientific advancement when conducted for research. Clinicians and patients often portrayed embryo selection and prioritization as a means to: a) having a healthy (genetically-related) child, b) focusing on the “best” embryo, c) minimizing or preventing a future individual’s risk of developing a health condition, and/or d) improving society by reducing disease and/or creating “productive” members of society. Furthermore, clinicians and patients considered selection and prioritization most relevant in cases of multiple available embryos and/or predisposition for a condition(s) that was perceived as severe, often in terms of repeated or high morbidity, high/early mortality, compromising quality of life, lack of treatment, early onset, and/or affecting others. In contrast, clinicians and patients considered preparation most relevant in cases of few available embryos, regardless of perceived condition severity. Some clinicians and patients considered family history of a condition(s) to be either a reason or prerequisite for PES benefit or utility, especially in terms of justifying selection against certain embryos or preparation for the birth of a child with specific genetic risks.

Potential concerns about PES

All 27 clinicians and 26 patients raised multiple potential, interrelated concerns about PES during the interview. Each set of thematically grouped concerns are listed in descending order of frequency across the entire sample of clinicians and patients. Notably, concerns over social harms were most numerous and frequent.

Social harms

The most common concern among all participants was the potential for different types of “biases.” Most often, this concern was in relation to embryo selection based on traits, with some clinicians and patients alluding to or specifically raising concerns about eugenics. Several clinicians and patients were concerned with political or subversive agendas, often referencing Nazi Germany, blue-eyed blonde Aryans, or creation of a “master race.” A few clinicians and patients worried that eugenic practices of selection following PES may (further) divide society or reduce human diversity. Additionally, some clinicians and patients raised concerns over bias inherent in the screening’s metrics (e.g., racial disparities in genome wide association studies) or the concept of measuring intelligence. Furthermore, a few patients and one clinician worried about potential physician bias in offering or counseling for PES; for example, offering it only to some patients or having personal perceptions influence how they counsel patients.

A common yet less frequent concern among clinicians and patients was the potential for loss of perspective as to what was important in life and/or IVF (e.g., valuing diversity and/or life itself, achieving pregnancy and live birth). Most of these concerns were made with respect to screening for traits, which was often considered trivial.

Another common yet less frequent concern among clinicians and patients was the economic aspects of PES. This concern was portrayed most often in terms of its added expense – which ultimately leads to unequal access to the technology – but also how the opportunity for profit drives its development.

Some clinicians and patients worried that knowledge about a selected embryo’s chances for developing a health condition or trait may negatively affect the parent-child relationship. Such negative effects may be due to resulting children either not living up to parental expectations or being treated as patients-in-waiting.

Finally, some participants raised concerns about PES’s consumerist aspects (e.g., designing babies; direct to consumer marketing) and the potential for PES to serve as a means for enhancement, in terms of creating “super” or “superior” people.

Individual harms

A common concern among clinicians and patients was the potential to harm IVF patients either psychologically or physically. Psychological harm was framed in terms of confusion, stress, or anxiety over PES information and what to do with it; disappointment if expectations are not met; and/or exploitation by companies offering PES. A few clinicians worried about PES’s potential to physically harm patients in cases when they electively seek to undergo IVF, with its associated risks, just to use PES, or undergo additional cycles of IVF to create or maximize embryo options. Such cases were portrayed as excessive.

Several patients, and even more clinicians, raised concerns about the potential for PES to limit or even eliminate embryos that patients perceive as acceptable for transfer. This concern reflected the use of PES for embryo selection in an IVF context where embryo availability is already limited.

Clinical and technical aspects

A common concern among clinicians and patients was over the uncertain or probabilistic nature of PES. Clinicians particularly worried that this would complicate counseling, especially amid time constraints, and/or lead to excessive IVF in pursuit of the “perfect” embryo. A few clinicians were unsure how to counsel patients about PES and worried about the lack of data and professional guidance on how to do so.

Clinicians’ most common concern, which several patients also shared, was a lack of data, usually with respect to the predictive value or generalizability of PES, because not enough research (e.g., long-term, prospective studies) has been conducted to support its clinical use. Some clinicians and patients were concerned specifically about a lack of data regarding antagonistic pleiotropy (i.e., genetic variants that lead to multiple phenotypes affecting evolutionary fitness in opposite ways) and/or more generally about the imperfect state of knowledge regarding genetics, human development, and health effects of IVF conception.

Some participants noted the multifactorial nature (i.e., interactions among genes, environment, and lifestyle) of polygenic conditions and traits as challenging the utility of PES for embryo selection. Often, this concern was made in association with screening embryos for cognitive traits (e.g., intelligence) and/or psychiatric conditions.

Some participants voiced general concerns about the potential of preimplantation genetic screening to physically harm the embryo(s). This was particularly acute for patients that experienced difficulties conceiving or those who ardently valued embryos’ potential for life.

Values and virtues

The concern of PES potentially leading to excessive or unethical embryo discard was common among clinicians but less so among patients. Most clinicians and patients with this concern specifically worried about discarding embryos characterized as “healthy,” “normal,” “fine,” or “viable.” Some clinicians and a few patients were concerned about discard resulting from a strive for perfectionism, which may lead patients to undergo excessive rounds of IVF.

Only a few clinicians but more patients felt PES represented a lack of humility in terms of accepting limitations to human control and/or knowledge. Though this concern was most often made with respect to screening (and selection) for traits, it was sometimes made regarding PES in general or screening for (and selection against) health conditions.

Parameters and governance

A rather common concern among clinicians, but not as much for patients, was difficulty in setting limits as to what is acceptable to screen for in embryos and who should be permitted to use PES. Some clinicians and patients felt that screening embryos to select against those with increased genetic risk for manageable or treatable conditions was inappropriate because individuals at increased risk or even with the condition can lead fulfilling and healthy lives. Additionally, some felt that screening embryos to select against those with (increased genetic risk for) conditions with: a) adult onset is problematic because of the decades required for studies to validate the data and the potential for medicine to develop treatments by the time of onset, or b) low (absolute or relative) risk may not be worthwhile, considering the potential to modify such risk(s) via environment or lifestyle. Furthermore, several clinicians and patients noted the ever-changing contextual nature of classifying some traits as desirable and selecting embryos based on their likelihood for developing them.

Several clinicians felt embryo selection based on PES, particularly for traits, was not part of a physician’s role, which is focused on treating disease (i.e., infertility in the case of REIs). Hence, facilitating such selection would be beyond their medical scope.

A few participants worried about potential liability issues when selected embryos do not meet IVF patients’ expectations for their eventual children (e.g., of developing certain traits or not developing certain conditions).

DISCUSSION

This study, which is the first to compare clinician and patient perspectives of PES, yielded several noteworthy findings. First, there appears to be a gap between clinician and patient attitudes toward PES, whereby clinicians generally maintained reservations about such screening and patients indicated interest in it. This finding aligns with recent studies of American and European healthcare professionals’ attitudes toward PES (18,19), American IVF patients’ increasing use of preimplantation genetic testing (20), high acceptance of PES (21), and high uptake of PES when offered at no additional financial cost to patients that used PGT-A (22). Moreover, REIs’ greatest concern about the lack of available data to support PES may reflect their perceptions of the controversial widespread clinical implementation of PGT-A, which some have argued was premature (23,24).

Interestingly, though PES is marketed and usually discussed as a tool for embryo selection (7), we found that clinicians and patients sometimes envisioned PES being used to prepare for the birth of a predisposed or “affected” individual. Although the intentional or incidental transfer of embryos with pathogenic variants detected in preimplantation testing is rare (25), preparation has not been reported previously as a motivation or decisional factor for using preimplantation genetic testing (26). However, preparation has been considered a benefit or use of prenatal testing (27). Thus, a conflation between prenatal and preimplantation genetic testing may be a factor contributing to these comments. Further research is warranted to determine whether PES’s potential for preparation reflects a real or theoretical use of the screening information.

Another notable finding is the difference in opinion between screening embryos for conditions versus traits among both clinicians and patients, with far less support for traits. This finding aligns with previous measured stances of ASRM’s Ethics Committee regarding embryo sex disclosure and selection (28,29) and previous studies of pregnant women’s perspectives of noninvasive prenatal testing and whole genome sequencing (30,31). Yet some clinicians’ and patients’ references to certain conditions while discussing screening for traits blurred the distinction between these two categories. Perhaps it may be more apt to consider PES in terms of screening embryos for health related- and non-health related-traits, especially when deliberating on the potential guidance for it.

Relatedly, severity and definitions of health loom large in discussions of PES. Previous studies report condition severity is a main factor in deciding whether to use preimplantation genetic testing, and the ability to control or improve the health of one’s future child(ren) is a main motivation for using it (26,32). However, the constitution of severity and health is debatable (33–36). Though some scholars believe consensus on defining these terms is impossible (37), others propose developing an adaptable framework that incorporates biomedical, social, and personal meanings (38). Either way, the prospect of PES invites clinicians, IVF patients, and all of society to contemplate the meanings of these concepts.

Limitations

This qualitative study’s findings may be limited by social desirability response bias (i.e., answering questions in a manner that will be viewed favorably by others) and self-selection bias. Thus, its generalizability to other REIs and IVF patients may be limited. Furthermore, discussion of screening embryos for specific conditions and traits sometimes was prompted by the interviewer: a) citing examples of heart disease, cancer, depression, schizophrenia, height, hair color, and intelligence, and b) demonstrating a PES report, which included conditions such as diabetes and cancer (Appendices 1 and 2).

CONCLUSION

Despite patients’ interest in PES, clinicians feel such screening is premature for clinical application. Though now embryos can be screened for their genetic chances of developing polygenic conditions and traits, many clinicians and patients maintain different attitudes depending on what is specifically screened, even though the distinction between conditions and traits is not always clear-cut. This dual-use aspect will prove challenging for governing PES. Professional societies are best positioned to develop guidelines for navigating the uncertain terrain of PES, which is already commercially available. Moreover, there should be greater discussion within medicine and society over meanings of “severe” and “health.”

Attestation Statement:

• Data regarding any of the subjects in the study has not been previously published unless specified.

• Data will be made available to the editors of the journal for review or query upon request.

Data Sharing Statement:

Appendices 1 and 2 will be available as supplemental materials upon publication. De-identified coded transcript excerpts will be made available upon reasonable request to the corresponding author.