原発性線毛運動不全における妊娠の課題

タイトル: Infertility and pregnancy outcomes among adults with primary ciliary dyskinesia

概要: Study questionWhat 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 answerWe 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 alreadyPCD 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, durationWe 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, methodsWe 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 chance265 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 cautionThe 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 findingsThe 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 Primare Ciliare 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 numberClinicalTrials.gov ID NCT04602481 What does this mean for patients?Primary ciliary dyskinesia (PCD) is a rare genetic disease. People who live with it can have problems conceiving. It is unclear how many people with PCD struggle to have children, and how many can only have children with help. We also do not know if women with PCD more often have ectopic pregnancies (= pregnancies outside of the uterus) than the general population. How did we answer these questions? We sent a questionnaire about fertility to all participants in the Living with PCD study. The Living with PCD study is an online study. It collects information directly from people with PCD from all over the world. How many people with PCD struggled to have children? Eight out of ten men and six out of ten women had problems conceiving. How many were successful with help? Among those who struggled, two out of three were able to have a child with help of fertility treatments. Did women with PCD more often have ectopic pregnancies? Women with PCD more often had an ectopic pregnancy than the general population. In our study, seven out of 100 pregnancies were ectopic, compared to only two in 100 pregnancies in the general population. We believe that more people with fertility problems completed our questionnaire. Thus, the true risk of ectopic pregnancy in PCD might be lower than we found in our study. But ectopic pregnancies can lead to serious complications. Thus, the authors of this paper think that fertility specialists should inform women with PCD about their increased risk. Women with PCD should see their gynaecologist early in their pregnancy to confirm that the pregnancy is inside the uterus. The authors suggest to address fertility problems in routine PCD care, with the help of fertility specialists.