Study question: What is the prevalence of infertility and ectopic pregnancies among individuals with primary ciliary dyskinesia (PCD), to what extent do they benefit from medically assisted reproduction (MAR), and how does fertility differ by affected PCD gene? Summary answer: We found that 39 of 50 men (78%) and 72 of 118 women (61%) with PCD were infertile. MAR was effective in infertile individuals, with around two-thirds of them successfully conceiving with MAR. Women with PCD had an increased risk of ectopic pregnancies (7.6 per 100 pregnancies, 95% CI 4.7-12.2). Our results suggest that fertility status in PCD differs by affected PCD gene. What is known already: PCD is a heterogeneous multiorgan disease caused by mutations in genes required for the function and structure of motile cilia. Previous studies identified a link between PCD and infertility, but original data on prevalence of infertility and risk of ectopic pregnancies, the use and efficacy of MAR and the association of fertility with PCD genotype, are extremely limited. Study design, size, duration: We performed a cross-sectional survey about fertility within the Living with PCD study (formerly COVID-PCD). Living with PCD is an international, online, participatory study that collects information directly from people with PCD. People with PCD of any age from anywhere in the world can participate in the study. At the time of the survey, 482 adults with PCD were registered within the Living with PCD study. Participants/materials, setting, methods: We sent a questionnaire on fertility on July 12, 2022, to all participants older than 18 years enrolled in the Living with PCD study. The fertility questionnaire covered topics related to pregnancy attempts, use of MAR, and pregnancy outcomes. Data was collected via the Research Electronic Data Capture (REDCap) platform. We defined infertility as failure to achieve a clinical pregnancy after 12 months or use of MAR for at least one pregnancy (Zegers-Hochschild et al., 2017). Main results and the role of chance: 265 of 482 adult participants (55%) completed the fertility questionnaire. Among 168 adults who had tried to conceive, 72 (61%) women and 39 (78%) men were infertile. Of the infertile men, 28 had tried MAR, and 17 of them (61%) fathered a child with the help of MAR. Among infertile women, 59 had used MAR, and 41 of them (69%) became pregnant with the help of MAR. In our population, women with PCD showed a relatively high risk of ectopic pregnancies: 1 in 10 women who became pregnant had at least one ectopic pregnancy and 7.6% of pregnancies were ectopic (95% CI 4.7-12.2). We evaluated the association between fertility and affected PCD genes in 46 individuals (11 men, 35 women) with available genetic and fertility information, and found differences between genotypes e.g. all 5 women with a mutation in CCDC40 were infertile and all 5 with DNAH11 were fertile. Limitations, reasons for caution: The study has limitations, including potential selection bias as people experiencing problems with fertility might be more likely to fill in the questionnaire, which may have influenced our prevalence estimates. We were unable to validate clinical data obtained from participant self-reports due to the anonymous study design, which is likely to lead to recall bias. Wider implications of the findings: The study underlines the need for addressing infertility in routine PCD care, with a focus on informing individuals with PCD about their increased risk. It emphasizes the utility and efficacy of MAR in PCD-related infertility. Additionally, women attempting conception should be made aware of the increased risk of ectopic pregnancies and seek systematic early consultation to confirm intrauterine pregnancy. Fertility, efficacy of MAR and risk for adverse pregnancy outcomes differ between people with PCD—depending on genotypes—, and close monitoring and support might be needed from fertility specialist to increase chances of successful conception. Study funding/competing interest(s): Our research was funded by the Swiss National Science Foundation, Switzerland (SNSF 320030B_192804/1), the Swiss Lung Association, Switzerland (2021-08_Pedersen), and we also received support from the PCD Foundation, United States; the Verein Kartagener Syndrom und Primäre Ciliäre Dyskinesie, Germany; the PCD Support UK, United Kingdom; and PCD Australia, Australia. M. Goutaki received funding from the Swiss National Science Foundation, Switzerland (PZ00P3_185923). B. Maitre participates in the RaDiCo-DCP funded by INSERM France. Study authors participate in the BEAT-PCD Clinical Research Collaboration supported by the European Respiratory Society. All authors declare no conflict of interest. Trial registration number: ClinicalTrials.gov ID NCT04602481

The authors have declared no competing interest.

Our research was funded by the Swiss National Science Foundation, Switzerland (SNSF 320030B_192804/1), the Swiss Lung Association, Switzerland (2021-08_Pedersen), and we also received support from the PCD Foundation, United States; the Verein Kartagener Syndrom und Primäre Ciliäre Dyskinesie, Germany; PCD Support UK, United Kingdom; and PCD Australia, Australia. M. Goutaki received funding from the Swiss National Science Foundation, Switzerland (PZ00P3_185923). B. Maitre participates in the RaDiCo-DCP funded by INSERM France. Study authors participate in the BEAT-PCD Clinical Research Collaboration supported by the European Respiratory Society.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The cantonal ethics committee of Bern, Switzerland, approved the study (study ID: 2020-00830).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Living with PCD data is available upon reasonable request by contacting Claudia Kuehni (claudia.kuehni@unibe.ch).