Decision‐Making Around Preimplantation Genetic Testing by Individuals With Neurofibromatosis Type I: A Qualitative Study

ABSTRACT

Preimplantation genetic testing for monogenic conditions (PGT‐M) with in vitro fertilization (IVF) is a reproductive technology that reduces the chance of passing down known genetic variants to future children. While prior research has explored reproductive decision‐making for individuals with neurofibromatosis Type 1 (NF1), few studies describe the factors that influence their choices to pursue or not pursue IVF with PGT‐M. Adults with NF1 in the United States who had received reproductive counseling around IVF with PGT‐M were recruited from the Children's Tumor Foundation NF Registry. We conducted virtual semi‐structured qualitative interviews that assessed participants' reproductive choices and lived experiences in the context of NF1. Transcripts were de‐identified, coded, and thematically analyzed using the Framework Method. Coding matrices were created to synthesize data and generate themes. We interviewed 20 individuals with NF1: 12 who pursued and 8 who did not pursue IVF with PGT‐M. Four key themes emerged around reproductive decision‐making: (1) Personal values and preferences, (2) Practical considerations, (3) Input from others, and (4) Retrospective feelings and future considerations. The choice of whether to pursue IVF with PGT‐M for NF1 is a personal and nuanced decision affected by the emotional, financial, and time commitments of IVF with PGT‐M. During counseling, clinicians should consider a patient's family history of NF1 and address the clinical variability of NF1 to facilitate reproductive decision‐making. Many participants reported increased neurofibroma growth during IVF or pregnancy and expressed concerns about undergoing IVF or carrying future pregnancies due to this perceived risk. Future research should address these concerns to improve reproductive counseling for individuals with NF1.

What is Known About This Topic

NF1 is a hereditary condition with highly variable clinical expression, and prior studies show mixed evidence on how personal disease severity and family history influence reproductive decision‐making. Although IVF with PGT‐M is an available option to reduce the chance of transmission, limited research has examined the specific factors that shape the decisions of patients with NF1 to pursue or not pursue this technology.

What This Paper Adds to the Topic

This study provides one of the first U.S.‐based, in‐depth examinations of how individuals with NF1 navigate decisions about IVF with PGT‐M, identifying both previously recognized influences and novel factors such as concerns about cutaneous neurofibroma growth and challenges surrounding decision‐making about affected embryos. It also highlights the role of family history in PGT‐M decision‐making and underscores the need for tailored reproductive counseling and emotional support.

1. Introduction

Neurofibromatosis Type 1 (NF1) is a hereditary syndrome characterized by features such as cutaneous neurofibromas (small benign tumors), plexiform neurofibromas (often larger, with a small risk of malignancy), learning differences, and scoliosis (Friedman 2022). This condition is inherited in an autosomal dominant manner with a 50% chance of transmission to offspring. NF1 has complete penetrance but the range and severity of clinical features are unpredictable, even among family members with the same genetic variant (Radtke et al. 2007). Preimplantation genetic testing for monogenic conditions (PGT‐M) with in vitro fertilization (IVF) is a reproductive option available to test embryos for the familial NF1 variant with the goal of reducing the chance of a disease‐causing variant being passed down from a parent to a child (De Rycke and Berckmoes 2020). While some literature is available on reproductive decision‐making, prenatal diagnosis, and prenatal genetic counseling for individuals with NF1 (Benjamin et al. 1993; Cesaretti et al. 2013; Farhi et al. 2008; Gonzalez et al. 2025; Kaplan et al. 2025; Kowal and Domaradzki 2025; Ponder et al. 1998; Terzi et al. 2009), few studies have focused specifically on PGT‐M for people with NF1 (Crawford et al. 2015; Gonzalez et al. 2025; Merker et al. 2015; Vernimmen et al. 2023, 2026).

Multiple factors influence the reproductive decisions of patients with NF1. Variability in the clinical expression of the condition is a major consideration (Benjamin et al. 1993; Kaplan et al. 2025; Ponder et al. 1998). There is mixed evidence for (Ponder et al. 1998; Kowal and Domaradzki 2025) and against (Benjamin et al. 1993; Farhi et al. 2008) the role of an individual's personal symptom severity on reproductive decision‐making and/or demand for prenatal diagnosis. Similarly, the impact of a family history of NF1 on reproductive decisions has mixed evidence in the literature. An Italy‐based study by Cesaretti et al. (2013) noted that patients with a de novo variant were more likely to seek prenatal diagnosis than patients with a family history of NF1. Other studies showed that the presence or absence of family history of NF1 had little effect on reproductive decision‐making (Ponder et al. 1998) or desire for prenatal diagnosis (Farhi et al. 2008). These discordant results likely reflect both the complexity of reproductive decision‐making across multiple factors and differences in study timing and location, motivating the need for further research to understand how individuals with NF1 make reproductive decisions.

Very few contemporary studies on reproductive decision‐making in individuals with NF1 touch specifically on the decision‐making process around IVF with PGT‐M. Gonzalez et al. (2025) conducted focus groups of Australian adults with NF1 or schwannomatosis and noted several major facilitators and barriers to pursuing IVF with PGT‐M. These included a desire to avoid passing NF1 on to a child, the financial cost of IVF with PGT‐M, and the expected emotional burden of IVF treatment and related health concerns. In a retrospective electronic medical record review conducted across three PGT centers in the Netherlands, Belgium, and France, Vernimmen et al. (2023) found that of 140 couples with NF1 who requested PGT‐M, 82 couples decided to proceed with PGT‐M, 43 couples opted out, and 15 could not proceed with PGT‐M. Reasons couples opted out of IVF with PGT‐M included the long trajectory for the PGT‐M process, spontaneous pregnancy, ending of the relationship, and other social and/or financial factors. For couples who could not proceed with PGT‐M, reasons included failure to identify the molecular cause of NF1, ineligibility for IVF treatment, or maternal health concerns.

However, there is still a paucity of literature evaluating the specific motives for people with NF1 to pursue or not pursue IVF with PGT‐M. Much of the existing literature around reproductive decision‐making for individuals with NF1 is from studies that were conducted over a decade ago and/or outside of the United States (U.S.). A few of the studies conducted prior to the broader availability of PGT‐M center their focus on decision‐making around prenatal diagnostic testing, failing to capture the decision‐making process unique to preimplantation genetic testing. Our study aims to fill this gap by using qualitative research methods to explore and describe the factors that influence people with NF1 to pursue or not pursue PGT‐M in the U.S. Our aim was to learn about the reproductive decision‐making process of individuals with NF1, explore why couples decide to move forward with PGT‐M or not, and better understand what individuals with NF1 would like to gain from a preconception counseling experience.

2. Methods

This qualitative study is reported according to the consolidated criteria for reporting qualitative research (COREQ) guidelines (Tong et al. 2007). Within a post‐positivist paradigm, the research team sought to understand concrete factors that impacted NF1 patients' reproductive decision‐making and generate hypotheses about how disease severity and family history may or may not influence these choices, while also acknowledging that retrospective decisions can only be partially understood due to patients' evolving perspectives and researchers' own influence in eliciting and interpreting data. All study procedures were approved by the Mass General Brigham (MGB) Institutional Review Board (Protocol: 2024P001799).

2.1. Recruitment

Participants were recruited through the Children's Tumor Foundation (CTF) NF Registry (Seidlin et al. 2017). The NF Registry is an Institutional Review Board‐approved, online registry for adults and parents/guardians of children with neurofibromatosis and schwannomatosis. All participants signed consent to participate in the registry and indicated if they would like to be contacted about future research opportunities. CTF staff notified potentially eligible NF Registry participants about the study via email. Interested participants were directed to complete an online pre‐screening survey to determine eligibility and provide their contact information. Our study staff then verbally consented eligible participants and shared a consent fact sheet describing the study in a follow‐up confirmation email. Once consented, participants were asked to complete a demographic survey to collect information on sociodemographic and clinical characteristics [i.e., age, gender, sex, ethnicity/race, level of education, household income, perceived severity of NF1 (mild, moderate, severe), age of diagnosis of NF1, time (in years) since receiving reproductive or family planning counseling, number of children in total, number of children conceived through IVF with PGT‐M, and health insurance status at the time of IVF with PGT‐M counseling].

2.2. Study Participants

Eligibility criteria included adults with a diagnosis of NF1 currently residing in the United States who were willing and able to complete a virtual interview in English, and who previously received reproductive or family planning counseling from a health care professional. We recruited a purposive sample of up to 20 participants, with the initial goal of recruiting 10 participants opting to pursue and 10 participants opting not to pursue IVF with PGT‐M. This pragmatic target was based on prior empirical evidence that data saturation typically occurs by this point, although no formal assessment of saturation was conducted during data analysis for this study (Guest et al. 2006, 2020).

2.3. Data Collection

Virtual interviews were conducted by the first author (S.L.C., a female genetic counseling student who completed graduate coursework and one‐on‐one training in qualitative methods) using Microsoft Teams. There was no relationship between the interviewer and participants prior to the study. At study start, participants were informed of the graduate program the interviewer was associated with and informed that the goal of the research was to learn about what factors people with NF1 consider when deciding whether or not to pursue IVF with PGT‐M and how genetic counselors can provide better reproductive counseling to people with NF1.

Interviews followed a semi‐structured interview guide (Appendix S1). Interview questions and prompts were developed and reviewed by all authors prior to initiating data collection; this includes team members with prior clinical and research experience with NF1 but did include a formal piloting process with patients. Topics included open‐ended questions on participants' experiences with NF1, experiences with family planning and reproductive counseling, and their consideration of IVF with PGT‐M as a reproductive option. Interviews ranged from 21 to 54 min; no repeat interviews were required and there were no non‐participants present during the interviews. All interviews were video‐ and audio‐recorded, transcribed using Microsoft Teams and corrected by study staff as needed, and de‐identified with participant consent. Transcripts were not returned to participants for comments or corrections.

2.4. Data Analysis

We used the Framework Method to analyze our data (Gale et al. 2013). This method provides a structured technique to reduce and display insights from coded data that facilitates understanding of within‐participant reproductive decision‐making captured across multiple codes, as well as across‐participant comparison of how experiences may differ between those who did and did not pursue PGT‐M. The first author took field notes during data collection to identify initial categories of interest. After completion of all data collection, all four co‐authors reviewed interview transcripts to familiarize themselves with the data and inductively identify important categories of information (i.e., codes). A working analytical framework with code names and definitions was iteratively refined as the team independently coded three transcripts and discussed any coding discrepancies. The final analytic framework was applied to remaining transcripts by the first author using Dedoose v9.2.22. To ensure reflexivity, the research team met periodically during this time to review new or unclear concepts and discuss our differing perspectives to ensure consistent interpretation of codes.

The final analytical framework had seven major categories describing participants' prior experiences with NF1, thoughts on and experiences with various family planning options, description of their reproductive decision‐making process, factors that were described as relevant to their decision‐making, experiences with reproductive counseling, other support or resources utilized, and advice for others undergoing this process. Within these categories, the first author created framework matrices (with participants on the x‐axis, interview codes on the y‐axis, and summarized data with illustrative quotes in each cell) to synthesize data and compare coded data within and across each stratum of interviewees (i.e., individuals opting or not opting to pursue IVF with PGT‐M). Finally, the research team reviewed coding matrices to generate larger, cross‐cutting themes derived from the data that illuminated the factors that people with NF1 consider when deciding whether to pursue IVF with PGT‐M. Participants did not provide feedback on these findings.

2.5. Positionality Statement

The research team included a genetic counseling student, two practicing genetic counselors with clinical experience counseling NF1 patients considering PGT‐M, and a health services researcher at an NF1 clinic who has previously published on PGT‐M outcomes in NF1. Based on our prior clinical and research training, all team members viewed PGT‐M as one of several possible family‐building strategies that may be suitable for people with NF1 and none held religious or moral objections to PGT‐M as a healthcare option. The team had diversity in parental status, including people who have children, are child‐free, and who are not yet decided; however, all team members were heterosexual, cis women living in the U.S., which may have influenced our interpretations of participants' reproductive journeys. We attempted to mitigate this bias by interrogating unclear coding choices during team meetings and re‐reading participant accounts to ensure final themes accurately reflected participants' own views of their decision‐making processes.

3. Results

3.1. Participant Recruitment and Demographics

Of the 134 pre‐screening survey responses received, 53 were complete and eligible for an interview. Email invitations were consecutively extended to 45 respondents, and one phone call was made for follow‐up in the event of no email response. Twenty‐five people were scheduled for an interview and 20 completed an interview (Figure 1). Participants had a median age of 41 years (range, 23–54 years); additional demographics and reproductive characteristics are summarized in Tables 1 and 2.

FIGURE 1.

Flowchart of study participants.

TABLE 1.

Participant demographic characteristics.

Participant characteristics	n = 20	%
Sex assigned at birth
Female	15	75
Male	5	25
Race/ethnicity (select all that apply)
African American/Black	2	9
Latine/Hispanic	4	18
East/Southeast Asian	1	5
West Indian	1	5
White	14	63
Age of diagnosis of NF1
0–10 years old	15	75
11–17 years old	3	15
18–24 years old	2	10
25–34 years old	1	5
Perceived severity of NF1
Mild	6	30
Moderate	12	60
Severe	2	10
Family history of NF1
Had a family history of NF1	10	50
Did not have a family history of NF1 (De Novo)	10	50
Highest level of education
Less than a high school diploma	2	10
High school diploma or equivalent	2	10
Undergraduate degree	6	30
Graduate or professional degree	10	50
Household Income
Less than $30,000	2	10
$30,000–$59,999	2	10
$60,000–$89,999	3	15
$90,000–$149,999	7	35
$150,000 or more	5	25
Declined to answer	1	5
Health insurance status at time of IVF/PGT‐M counseling
Insurance through a current or former employer or union	16	80
Medicaid	1	5
Other type of health insurance coverage	1	5
Not sure	1	5
Declined to answer	1	5

TABLE 2.

Participant reproductive characteristics.

	n = 20	%
Reproductive decisions
Pursued IVF with PGT‐M	12	60
Completed IVF with PGT‐M	7	35
In process of IVF with PGT‐M at time of interview	3	15
Pre‐starting IVF with PGT‐M at time of interview	2	10
Did Not Pursue IVF with PGT‐M	8	40
Natural conception	8	40
Prenatal diagnostic testing	2	10
Adoption	1	5
Surrogacy	2	10
Length of time since reproductive counseling
In the past 0–3 years	9	45
In the past 4–6 years	3	15
In the past 7–10 years	1	5
In the past 11+ years	6	30
Declined to answer	1	5

Of the 20 participants, 12 had chosen to pursue IVF with PGT‐M. Of these 12 participants, nearly all (10/12) had no family history of NF1. The two participants who had a family history of NF1 both had a self‐reported “Moderate” severity of NF1 and noted the development of malignant cancers associated with NF1 in their affected family members. Of the 8 participants who had chosen not to pursue IVF with PGT‐M, all (8/8) reported a family history of NF1.

3.2. Thematic Analysis

Four key themes emerged around factors that influence reproductive decision‐making about IVF with PGT‐M: (1) Personal values and preferences, (2) Practical considerations, (3) Input from others, and (4) Retrospective feelings and future considerations.

3.2.1. Theme 1: Personal Values and Preferences

3.2.1.1. Opinions About Passing on NF1 to Future Generations

Many participants who pursued IVF with PGT‐M cited a desire to avoid passing on NF1 to future children. Some considered their personal NF1 experiences and those of their affected family members as a measure of how comfortable they might feel having a child with NF1.

I know what I had to struggle with and I've seen my mom struggle with so much that that's not something I would want to put on someone else. Like my mom, I know she suffered for like, at least a majority of my life that I was there for, and it was a lot for her. And just the complications, not just with cancer or, you have to remove tumors, but the cognitive issues that go along with it… I feel like it seems not fair to put that on somebody just because I want kids…. It's a 50/50 chance and I don't want to risk that. (Participant 20, Female, Family History of NF1, Pursued PGT‐M)

Others stated that they would not want to put their future children through what they experienced regarding health or social struggles.

NF has held me back from so many other things, so I didn't want it to hold me back from being a mom. But I knew that I wouldn't do it without PG[T], because I thought I felt like that would be very selfish to pass down something… I've never met anyone that loves NF that lives with it, so. I just knew that if I was gonna have kids, I at least needed to try my best to take that part away from them [and] do them right by not giving them NF. (Participant 10, Female, De Novo, Pursued PGT‐M)

Some participants who had pursued PGT‐M expressed concerns about the health, quality of life, and social outcomes of a child with NF1 and intended to give their future child the “best shot at life.” Many stated that they did not want to risk the unpredictable range of severity seen in NF1 or “roll the dice.”

I've seen pictures of individuals who have NF a lot worse than me with the fibromas all over their bodies and I just couldn't picture a child coming into this world, especially with today's society and how cruel people could be and just make fun of somebody. (Participant 6, Female, De Novo, Pursued PGT‐M)

However, others who pursued PGT‐M shared a different view on the manageability of NF1. One participant considered the course of her own NF1 and shared that it “didn't seem like such a horrible thing,” pointing out that a child could be born with any number of complications unrelated to NF1. Another participant reflected that he “would rather be here with NF than never had existed,” musing that he had some challenges but a “pretty good life.”

Several participants expressed a sense of responsibility to prevent passing NF1 on to future generations. Some used descriptors such as “selfish” or “not fair” to pass NF1 down, and cited the fear of “resentment” from a child or feeling guilt if they did pass on NF1 as motivators to pursue IVF with PGT‐M. Two participants who had shared a desire to prevent passing on NF1 to a child and who both conceived naturally disclosed that they pursued prenatal diagnostic testing, such as amniocentesis and chorionic villus sampling (CVS), to be certain about whether the pregnancy had inherited NF1. One of these participants had a child that was not affected with NF1, and the other was awaiting diagnostic testing results at the time of the interview. Other participants, both who pursued and did not pursue PGT‐M, declined prenatal diagnostic testing options because of the associated miscarriage risk and the intent to continue carrying a pregnancy regardless of results.

3.2.1.2. Beliefs and Philosophy

Some participants alluded to religious, spiritual, or existential beliefs when making reproductive decisions. Some participants who did not pursue PGT‐M mentioned “faith” or “used prayer” as factors in the decision‐making process. One decided to conceive naturally and “put it in the Lord's hands.”

One participant pointed out that IVF and PGT‐M could be seen as invasive or unnatural, as “reproduction is a distinct act”. Of the participants who pursued PGT‐M, some used personal philosophies to guide processing of information and events throughout the IVF and PGT‐M process. One participant stated that “everything happens for a reason” regarding being unable to pursue IVF with PGT‐M due to logistical barriers, and that some things are “meant” or “not meant to be” concerning egg retrieval outcomes or successful IVF transfers.

3.2.1.3. Views on Biological Children and Family Size

Several participants expressed preferences around having biological children. Some pursued PGT‐M and declined use of egg or sperm donors to ensure that their child was conceived with contributions of genetic material from the participant and their reproductive partner. A few participants shared that they did not pursue adoption as a first option, reasoning that they might have “less control” over the outcome and health of a child who is adopted. However, other participants were more willing to consider alternative approaches. One participant who used an egg donor and surrogate shared in reference to her daughter, “she may not genetically be mine, but she's obviously still, you know, I'm still her mom.” Another participant considering adoption shared that she works in the NICU and sees “how many children need a good home.”

Some participants described their ideal family size as a guiding factor in selecting reproductive options. Many who wanted additional children considered or underwent IVF with PGT‐M for another pregnancy, and others brought up adoption or surrogacy as options they would consider if they were unable to pursue IVF and PGT‐M due to financial cost or medical risk to self.

We both know that we're not done, that we want more, but we're kind of at the point, like, OK, we've already passed it on twice. What do we do…? Our mindsets changed just a little bit. We still might try, but if we can… somehow get insurance to cover some of it, that would be really nice…. Or I don't know if adoption is in the cards. (Participant 4, Female, Family History of NF1, Did Not Pursue PGT‐M)

3.2.2. Theme 2: Practical Considerations

3.2.2.1. Cost

Almost unanimously, participants acknowledged the high cost of IVF and PGT‐M, with many citing financial costs as a major factor in their reproductive decision‐making. Many compared the long‐term expense to insurance companies and the healthcare system for the care of a child with NF1 to the cost of IVF with PGT‐M for prevention of passing down NF1 to future generations.

Some participants received coverage through insurance or had the financial means to pay out of pocket for IVF and cited these as motivators for pursuing IVF. A couple of participants mentioned that they put off buying a house to pay for the IVF process. One participant did not disclose their IVF journey to friends or family due to the fear of receiving judgment from or burdening others with their financial decisions:

We don't want my parents to be wondering, why are we wasting our money like this, right? They might have had different thoughts about it and what we should do, and we didn't want extra input on our decisions. (Participant 1, Female, Family History of NF1, Pursued PGT‐M)

3.2.2.2. Risk to Self

Participants considered potential health risks and complications related to pregnancy and the perceived impact of IVF and/or pregnancy on the course of their NF1.

Of the 15 female participants, 10 mentioned the topic of perceived tumor growth and increase in the number of neurofibromas during IVF and/or pregnancy. Half (5/10) reported experiencing an increase in the number and size of neurofibromas during pregnancy and/or IVF, and the other half (5/10) factored concerns around potential tumor growth during future pregnancies or IVF rounds into their decision‐making.

The hormonal relationship, I wonder about, because I had an increase in neurofibromas when I was on the pill, I had another surge of neurofibromas when I was pregnant with my son, and then I had another huge surge of neurofibromas when I was injecting hormones to do IVF…. I wonder about choosing IVF over natural childbirth in the instance of trying to prevent a pregnancy that has a child with NF, if the course of your own disorder is going to be dramatically different. (Participant 7, Female, De Novo, Pursued PGT‐M)

One participant wanted to avoid carrying a pregnancy as she felt it would worsen her NF1 symptoms, reasoning that she wanted to be healthy enough to take care of a child, enjoy an active lifestyle, and contribute equally to parenting with her partner. One participant considered surrogacy to avoid pausing necessary medications during pregnancy. A few participants were advised by clinicians not to carry a pregnancy due to medical risk involving tumor location, scoliosis, or potential increased tumor growth.

They basically told me, no, I could not carry. Specifically because of a tumor I have located, in the, near the uterus… [then we] flew out to [Clinic] and the guy said the same thing. It's like, if you were to get pregnant, it's basically a death wish…. So, then it was like, ‘OK, I can't carry…. Like we still want children. What are we gonna do?’ (Participant 9, Female, De Novo, Pursued PGT‐M)

3.2.2.3. Success Rates

Many participants considered the success rates of IVF and PGT‐M in their decision‐making, including the accuracy of PGT‐M in detecting unaffected embryos and the chances of success of an IVF cycle. Some weighed the financial burden of an IVF cycle with the chances of having both euploid, unaffected embryos and a successful transfer.

If we were to pay 30 grand for the PGT and be like my friend and not have it work, or I'm part of a NF Facebook page and… there's a small percentage who had success in the first round, but there was a lot of them [who] said it took them two to three rounds… I cannot afford that. (Participant 4, Female, Family History of NF1, Did Not Pursue PGT‐M)

Many navigated emotions around success rates, which included anxiety around the probability of embryos being affected or aneuploid (having extra or missing chromosomes) and the chances of a successful embryo transfer.

We were like, all right, we got 10 [embryos]. We felt incredibly optimistic…. And then we get back out of the 10, one's viable…. That was so hard because we're like, “Oh my God, what if this one doesn't take? … If this is our one shot, this round, if this one doesn't take, then we're gonna have to start all over”. (Participant 15, Male, De Novo, Pursued PGT‐M)

Participants also factored in reproductive age and infertility when considering success rates and making decisions around reproductive options. Overall, these practical and logistical considerations acted as both barriers and motivators to pursue and undergo PGT‐M (Figure 2).

FIGURE 2.

Barriers and motivators to pursue PGT‐M. Panel (A) Pathways of participants who did not pursue IVF (in vitro fertilization) with PGT‐M (preimplantation genetic testing for monogenic conditions). Panel (B) Pathways of participants who did pursue PGT‐M. Motivators to pursue PGT‐M are denoted by diamonds, barriers to pursuing PGT‐M are denoted by hexagons, and all other events are denoted by rectangles.

3.2.3. Theme 3: Input From Others

Participants heavily weighed preferences and advice from reproductive partners and clinicians in their decision‐making around PGT‐M. They also considered input from family members, friends, and colleagues, as well as the experiences of others with NF1 who underwent IVF with PGT‐M, although input from these broader communities did not appear to directly factor into the final decision to pursue or not pursue PGT‐M.

3.2.3.1. Reproductive Partner

Most participants received support from and reached mutual agreement with their reproductive partners regarding reproductive decision‐making. Input from reproductive partners overlapped with previous themes identified by participants (Table 3).

TABLE 3.

Input from reproductive partners.

Theme	Code	Quote
Personal Values and Preferences	Opinions about passing NF1 on to future generations	“I think what my husband and I ultimately decided was that we would feel so horrible if our children… knew that we could have prevented, like if they had it worse than I did, we would feel terrible, like, ‘cause we selfishly wanted kids so bad that we didn't do anything to, to try and take preventive measures to keep them from having this condition’. And I think that that was something my husband said was his biggest fear. Being resented by our child if we had passed on NF to them, and I felt the same way when he said that and I had never thought about it that way.” (Participant 13, Female, De Novo, Pursued PGT‐M)
		“I think we would want to probably still do [IVF] depending on how it would price out. Because I think it was pretty important to both of us to have that testing, and like I said, my husband's a very anxious person. So if we didn't know that, I think he would just be so anxious all the time, waiting until we had our children to find out if they had NF or not.” (Participant 5, Female, De Novo, Pursued PGT‐M)
	Beliefs and Philosophy	“[My husband] is also pretty religious, so I know that was kind of a hard step for him too, is to be OK and open to IVF, but it was hard in the beginning, but I think, you know, he understands now that it's the right path for us and the safest path and most responsible path.” (Participant 11, Female, De Novo, Pursued PGT‐M)
Practical Considerations	Risk to Self	“So, my wife and I, when we were dating, I was very upfront with her about NF1 and what it was.… She had PCOS, so to go through all of the hurdles of IVF just to avoid NF, and then with the PCOS making IVF much more difficult, we just thought, you know what? We're going to love our kids anyways and give this a go and not necessarily go that route.” (Participant 12, Male, Family History of NF1, Did Not Pursue PGT‐M)
		“So my neurologist told me… that I could have complications from being pregnant, and so he said, ‘In my opinion, you would be putting your life at risk.’ And you know, I'm talking to my husband, as much as we both want, wanted to have kids that were genetically ours, he goes, ‘It would be horrible if you weren't here or weren't able to be healthy to help take care of the kids and be the mom that you want to be.’” (Participant 13, Female, De Novo, Pursued PGT‐M)

One participant's partner was “not super worried about NF”. One participant reflected that her partner “would have been fine not having kids” and added that she believed her personal NF1 presentation directly affected her relationship with her partner, stating, “we don't have a normal, romantic marriage”. From a medical standpoint, some participants cited their reproductive partners' own health as factors that influenced decision‐making: one participant who had conceived naturally factored in the chance of passing on her spouse's diabetes risk when deciding not to have any future children, and one participant was deterred from pursuing IVF due to his spouse's Polycystic Ovary Syndrome (PCOS).

3.2.3.2. Clinicians

Some participants described how interactions with clinicians influenced their reproductive decision‐making; three participants were advised by clinicians to not carry a pregnancy due to medical risks, and one participant reflected on a negative interaction with a clinician in the past, during which she received judgment for pursuing IVF and PGT‐M.

3.2.3.3. Family, Friends, Colleagues, and the Broader NF1 and IVF Communities

Input from family, friends, and broader communities added emotional complexity to the decision‐making process around PGT‐M, but appeared to have less bearing on individuals' final decisions around PGT‐M compared to input from reproductive partners or clinicians. Many participants shared that they received unconditional support from family and friends during their reproductive journeys regardless of their decisions around PGT‐M. On the other hand, some participants felt a lack of support from family members throughout their reproductive journeys. This included perceived judgment about pursuing IVF with PGT‐M due to the financial cost and disapproval of the choice to have biological children without IVF with PGT‐M. Participants also noted the emotional impact of hearing about the experiences of others with NF1 who underwent IVF with PGT‐M. While some received valuable support from these interactions, others felt discouraged seeing others undergo multiple unsuccessful rounds of IVF or struggled when comparing their own difficulties to those who had more success in their IVF cycles. However, interactions with this broader community did not appear to directly influence decision‐making around PGT‐M for participants in this cohort.

3.2.4. Theme 4: Looking Back and Future Considerations

3.2.4.1. Retrospective Feelings

Participants reflected on their reproductive decisions and feelings throughout their reproductive journey. Many participants confirmed that they had “made the right decision” for themselves, with one participant who pursued an egg donor and surrogacy affirming that their choices were “worth every penny”. One participant who conceived naturally reflected on her daughter who was born with NF1: “there's a reason why she's here”.

Participants who undertook IVF reflected on the money and time spent on the IVF process. Many reflected on the lengths of their IVF journeys, with one participant saying, “it seems like it just lasted forever” and another wishing they were familiar with the length of the IVF process so that they could have started earlier. In addition, two participants who pursued IVF with PGT‐M struggled with decisions over the fate of embryos affected with NF1. One participant decided to keep embryos frozen indefinitely, positing that “maybe one day there will be a cure” and noting the lack of resources available for people navigating similar situations. Another participant emphasized that discussing the embryos that were not implanted was a “tough subject” and that he feels like a “hypocrite” that the affected embryos were discarded, concluding that decision‐making around affected embryos is personal.

I feel guilty that these children had, these embryos had NF and you know, they got discarded, and here I am with it. And then I also feel like even if we have another child, then if it has NF, then I discarded the other ones that had NF, it's, it's, it's really, it's really hard. (Participant 15, Male, De Novo, Pursued PGT‐M)

Finally, some participants who conceived naturally felt nervous about whether their child would have NF1 and, if so, the severity of their presentation. One participant felt hope that her children would be part of the future of NF1 care.

Even in the last 10 years, there's been so much more knowledge about it and findings and not cures, but like, things to help. I've just seen so many new things in the making to help shrink fibromas or whatever. I'm like, that is so promising for me that my children will have hope. …There's, there's a lot of things coming out and I'm just grateful that my children get to be a part of it and maybe get to be a part of research studies to help find a cure too. (Participant 4, Female, Family History of NF1, Did Not Pursue PGT‐M)

3.2.4.2. Advice and Support

Many participants emphasized that reproductive decision‐making is a personal choice and urged others to make decisions that they feel most comfortable with, assuring that “there is no wrong answer” and “every journey will look different.” One participant declared that no one should feel ashamed of any route they choose to take. Many mentioned that it is helpful to have a care team to consult and to take advantage of resources and support, with a few participants advising others to make informed choices, explore all available options, and adhere to evidence‐based information and resources.

In regard to pursuing IVF with PGT‐M, some participants suggested that it may be helpful to join support groups or talk to others who have already undergone the IVF and PGT‐M process to hear about different perspectives and experiences. One participant urged people to check if their fertility clinic offers scholarship‐type funding or financing for the IVF process. Multiple participants encouraged others to consider the emotional burden of IVF with PGT‐M, and one participant advised others to consider why they want to have children and what a child means to them.

Regarding natural conception, some participants advised parents to be prepared with knowledge and resources for a child with NF1. A few participants encouraged others planning to conceive naturally to “try [naturally] first, because the unexpected might happen” and to “go for it either way and don't be fearful”, with one participant offering that if a couple can't do IVF, “it will work out” and “everything happens for a reason”. One participant suggested that partners should be supportive of whoever is undergoing IVF; one assured that anyone experiencing struggles with infertility is not alone. Several participants mentioned that they disclosed their NF1 diagnosis early on in a serious relationship with a future reproductive partner to prepare them for expectations around family planning.

3.2.4.3. Experiences With Reproductive Counseling and Calls for Improvement

Participants added their thoughts about how their reproductive counseling could have been improved: a few mentioned that there should be more emphasis on IVF and PGT‐M as a reproductive option in OB/GYN visits, one wished that they had been connected with others who had undergone the IVF and PGT‐M process, and a few highlighted that clinicians should be non‐judgmental about reproductive decisions made by individuals with NF1. One participant reflected on a positive experience with a genetic counselor:

That was the first time I saw the genetic counselor down there and that was kind of a fun experience just because they kind of told me what the future could look like and how many different opportunities that I had. That it's not always black and white for every person with NF and a lot of people take different routes for different reasons. (Participant 11, Female, De Novo, Pursued PGT‐M)

4. Discussion

Our study explored the factors that shape the decision‐making of individuals with NF1 considering IVF and PGT‐M. To our knowledge, this is one of the first studies to describe and investigate the experiences of people with NF1 in the U.S. who did or did not pursue IVF with PGT‐M. Our findings identified several factors that appeared to influence decision‐making for individuals with NF1 that have been well‐described in previous studies, as well as novel factors not previously highlighted in the literature. In this sample, many participants voiced strong concerns about potential tumor growth during and after IVF and/or pregnancy, highlighting a striking disconnect between informal discourse and scientific evidence on this topic. Relevant to prior debates in the NF1 literature, the presence or absence of family history appeared to influence decision‐making around PGT‐M in this cohort. Lastly, our analysis revealed an emergent topic not previously described in the NF1 literature that has implications on reproductive counseling for people with NF1, as well as counseling for PGT‐M for other inherited conditions: navigation of feelings and logistics around the future of embryos that were affected or not transferred. This new finding highlights the need to emotionally prepare patients for the possible outcome of affected embryos and provide tangible guidance for subsequent steps during counseling for IVF with PGT‐M.

Practical and logistical considerations act as barriers and motivators to pursue PGT‐M for individuals with NF1 (Gonzalez et al. 2025; Ponder et al. 1998; Vernimmen et al. 2023). For participants who did not pursue PGT‐M, barriers included a lack of information or counseling around IVF and PGT‐M as reproductive options, financial cost of IVF and PGT‐M, and pregnancy‐related health risks for participants or their partners. For participants who pursued PGT‐M, barriers to undergoing or continuing IVF and PGT‐M included no pathogenic variant identified in the NF1 gene, an insufficient number of eggs retrieved for PGT‐M, or all embryos being affected or aneuploid (Figure 2). The anticipated length of an IVF journey did not appear to have a strong influence on decision‐making; rather, time spent on IVF and PGT‐M was brought up retrospectively by some participants who had pursued this route. Practical motivators to pursue PGT‐M included fertility issues that could also be assisted by IVF and sufficient insurance coverage for the IVF and PGT‐M process, highlighting that the financial cost of IVF with PGT‐M has a significant impact on reproductive decision‐making (Drazba et al. 2014; Gebhart et al. 2016; Gonzalez et al. 2025; Patton et al. 2023; Valdrez et al. 2014; Vernimmen et al. 2023). Health care professionals can provide balanced counseling about PGT‐M by setting expectations for logistical considerations while helping patients weigh these potential barriers against their personal values and preferences.

Regarding pregnancy‐related health risks, participants shared concerns about perceived progression of neurofibroma growth associated with pregnancy and/or IVF hormones. Some reported a growth in size and number of cutaneous neurofibromas when undergoing IVF or during pregnancy, and these experiences deterred a portion of these participants from pursuing IVF or carrying another pregnancy in the future. It is important to note that these are patient‐reported experiences, and definitive findings regarding a potential relationship between hormonal changes, pregnancy, and NF1 tumor progression are lacking. Although this potential increase in neurofibroma burden during pregnancy has been mentioned in some literature (Cesaretti et al. 2013; Dugoff and Sujansky 1996; Gonzalez et al. 2025; Vernimmen et al. 2023), data are discordant across past NF1 studies and case reports (Fishbein et al. 2007; Isikoglu et al. 2002; Posma et al. 2003; Roth et al. 2008; Well et al. 2020; Ly et al. 2023). As a potential association between pregnancy and tumor progression has yet to be conclusively proven and some NF1 clinicians do not believe one exists, this highlights a potential source of tension between clinician views and patient concerns that warrant discussion during genetic counseling visits. Furthermore, high‐quality, prospective research on this topic is critical to inform reproductive counseling and care for individuals with NF1.

The presence or absence of a family history of NF1 appeared to shape decisions around IVF with PGT‐M, with all eight participants who declined PGT‐M reporting a family history of NF1. To our knowledge, this relationship has only been reported twice in the NF1 literature, and in the context of pursuing prenatal diagnosis (Cesaretti et al. 2013; Pacot et al. 2024). A possible explanation for this pattern in the cohort is that individuals with a de novo or sporadic case (i.e., having no family history of NF1) may feel uncertain about potential clinical manifestations, fear serious complications, feel isolated, and/or lack NF1‐related information and exposure to others with NF1; conversely, individuals with a family history of NF1 may have familiarity with NF1 symptom management, as well as access to support and advice from affected family members (Cesaretti et al. 2013; Gonzalez et al. 2025). Further exploration into the differences in perspectives, strengths, support needs, and gaps in knowledge between individuals with and individuals without family members with NF1 is needed to understand how family history can shape decision‐making around PGT‐M.

Perceived severity of NF1 symptoms did not appear to have an influence on whether participants pursued IVF with PGT‐M in our cohort. Our findings support those of Benjamin et al. 1993 and Farhi et al. 2008 to suggest disease severity does not play a large role in most patients' decision‐making about PGT‐M. Explanations for this finding may include widespread cognizance of the clinical variability of NF1, along with practical factors that hold more weight in the decision‐making process, such as financial cost or lack of counseling around reproductive options. However, our sample did not include many participants with severe NF1; it may be that these individuals were less likely to plan on having children generally and thus excluded prior to considering PGT‐M.

However, the clinical variability of NF1 appeared to play a role in the decision‐making of many participants and was often considered in conjunction with participants' views on passing on NF1 to future generations. The 50% chance for a future child to inherit a familial variant, compounded by the inability to predict the range and severity of symptoms for an affected child, poses layers of uncertainty and complicates reproductive decision‐making for individuals with NF1 (Carrieri et al. 2016; Gonzalez et al. 2025; Kaplan et al. 2025; Ponder et al. 1998) and other conditions with clinical variability, such as inherited heart or vascular diseases (Patton et al. 2023; Yeates et al. 2022). Some participants pursued PGT‐M to avoid the chance of having a child with severe symptoms altogether and felt a sense of responsibility to prevent passing on NF1 to protect the health of future generations. This desire to avoid passing down an inherited condition is a strong motivator to pursue PGT‐M for individuals with NF1 (Crawford et al. 2015; Gonzalez et al. 2025) and other inherited conditions, such as Huntington's Disease, Hereditary Breast and Ovarian Cancer, Fragile X Syndrome, and hereditary visual loss (Decruyenaere et al. 2007; Fahy et al. 2023; Hughes et al. 2021; Nahshon et al. 2023; Patton et al. 2023; Redgrave and McNeill 2022; Yeates et al. 2022). This further highlights the importance of offering IVF with PGT‐M as an available option during reproductive counseling or even in specialty or primary care visits.

A poignant piece of the decision‐making process around PGT‐M noted by some participants was the difficulty of navigating the emotions and logistics associated with deciding the fate of affected embryos. To our knowledge, these concerns around decision‐making about affected embryos have not been explored in the NF1 literature. A few studies note patient perspectives on this topic in the context of PGT‐A (preimplantation genetic testing for aneuploidy, or extra or missing chromosomes) and/or PGT‐M for other conditions, such as inherited aortic and vascular diseases (Patton et al. 2023; Zhang et al. 2021). Related discussion around the available options for surplus cryopreserved embryos, including discarding, donating to research or the reproductive means of others, or keeping embryos in storage (Alexander et al. ; Khorshid et al. 2023; Thaldar and Edgcumbe 2024; Yue and MacKellar 2024; Zhang et al. 2021) may help inform logistical direction around decision‐making about affected embryos in the context of PGT‐M. Recognizing the potential emotional impact of this decision, genetic counselors should provide anticipatory psychosocial counseling to patients considering PGT‐M. Recognizing the potential emotional impact of this decision, genetic counselors should provide anticipatory psychosocial counseling to patients considering PGT‐M This should include explicitly discussing the possible outcome of affected embryos, preparing patients emotionally for decision‐making around these affected embryos, and providing support as they navigate decision‐making around transferring, discarding, storing, or donating affected embryos.

4.1. Limitations

Diagnosis of NF1, degree of symptom severity, and experience receiving reproductive counseling for IVF and PGT‐M were self‐reported by participants and not verified by clinical records. For participant recruitment, reproductive counseling was defined as counseling from a health care professional (including but not limited to primary care physicians, OBGYN practitioners, fertility specialists, and/or genetic counselors) about family planning or prenatal testing options. While all participants received information about PGT‐M, some participants appeared to lack formal counseling experience; these individuals each affirmed the perceived benefits of more formal reproductive counseling, emphasizing the need for earlier and increased access to this service.

Some participants reported that they had received reproductive counseling around IVF and PGT‐M more than 11 years ago, introducing a possibility for recall bias around reproductive experiences. Additionally, participants may have had different experiences with reproductive counseling and the IVF and PGT‐M process itself given the advancement of assisted reproductive technology and PGT‐M techniques over the past several decades (Chen et al. 2018; Parikh et al. 2018; Spits et al. 2005). To an extent, the format of individual interviews excludes the valuable perspectives of reproductive partners, especially for male participants who could not fully portray the perspectives of their unaffected partners who underwent IVF and/or carried a pregnancy.

Recruitment of individuals through the Children's Tumor Foundation NF Registry may have introduced potential selection bias, resulting in a cohort of individuals who may differ from other people with NF1 who are not connected to NF‐specific registries, research networks, or advocacy communities. Since participants were recruited from an online NF registry and interviews were conducted in English, this sample may also underrepresent individuals with lower health literacy, limited internet access, and limited English proficiency.

We did not collect information about which U.S. state participants received reproductive counseling in; in the United States, insurance coverage for IVF and PGT‐M varies across insurance plans and laws around IVF and PGT‐M vary across states (RESOLVE 2025a, 2025b). Our cohort also consisted mainly of White women who received an undergraduate education or higher; future research should explore decision‐making around PGT‐M in cohorts with more diversity in sex, race and ethnic background, level of education, and other characteristics that may introduce additional perspectives.

4.2. Conclusions

Our study explored the motives for people with NF1 in the United States to pursue or not pursue IVF with PGT‐M, providing a contemporary lens on this important reproductive counseling issue. Ultimately, our participants agreed that reproductive decision‐making is highly personal and requires an individual to evaluate their values and beliefs, along with their ability to manage the emotional, physical, and financial demands of IVF and PGT‐M and the time and effort required for the process. Many participants emphasized the importance of making well‐informed decisions and encouraged connection to genetic counseling to explore all available reproductive options, as well as support groups for participants seeking emotional support and additional perspectives. When providing counseling about IVF with PGT‐M, clinicians should take into account the personal values, preferences, and motivations of patients and their reproductive partners, including aspects like the presence or absence of family history that may influence a patient's familiarity with and outlook on NF1 and views on potential tumor progression during pregnancy. Our findings also highlight a need for guidance, resources, and support for individuals making decisions around the fate of affected embryos.

Author Contributions

Sidney L. Ching: conceptualization, investigation, writing – original draft, formal analysis. Kiley L. Delgado: conceptualization, writing – review and editing, formal analysis. Vanessa L. Merker: conceptualization, supervision, writing – review and editing, formal analysis. Stephanie R. Hicks: conceptualization, formal analysis, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

All procedures were conducted in accordance with the ethical standards of the Helsinki Declaration of 1975, as revised in 2000. This study was approved by the Massachusetts General Brigham Institutional Review Board.

Consent

Informed consent was obtained from all participants prior to their voluntary completion of a demographic survey and virtual qualitative interviews.

Conflicts of Interest

V.L.M. has received compensation from Alexion Pharmaceuticals for serving on advisory boards for topics related to NF1. The authors S.L.C., S.R.H. and K.L.D. declare no conflicts of interest.

Supporting information

Appendix S1: Interview guide.

Data Availability Statement

De‐identified data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.