As survival improves for individuals with inborn errors of immunity (IEI), increasing numbers reach reproductive age; however, reproductive health and family-planning needs in this population remain poorly defined. Immune dysfunction, infection susceptibility, endocrine abnormalities, and genetic uncertainty may affect fertility and reproductive decision-making. Clarifying these factors is essential to guide counseling, fertility preservation, and informed use of reproductive genetic options.
We conducted a retrospective, registry-based cohort study using our national IEI Registry, comprising over 450 clinically and genetically characterized patients. Extracted data included demographics, IEI phenotype and severity, treatment history, fertility status, miscarriage frequency, pregnancy and obstetric outcomes, hormonal profiles, infection burden, and utilization of reproductive genetic counseling. Patients were analyzed within three reproductive categories: (1) individuals whose disease severity or treatment-related complications limited fertility or pregnancy; (2) individuals whose immune or genetic background was associated with infertility, recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF); and (3) individuals with preserved fertility who experienced anxiety related to genetic transmission risk. Genetic findings were analyzed descriptively rather than used as the primary classification framework.
Substantial heterogeneity in reproductive outcomes was observed across IEI subtypes and reproductive categories. Patients in the first category frequently demonstrated gonadal dysfunction, impaired spermatogenesis, premature ovarian insufficiency, or pregnancy contraindications related to disease severity, cytotoxic therapies, chemotherapy exposure, or prior hematopoietic stem cell transplantation. The second category showed increased rates of infertility, RPL, RIF, and obstetric complications, particularly among patients with immune dysregulation, natural killer (NK) cell defects, inflammatory phenotypes, or endocrine involvement. Patients with definitive molecular diagnoses were more likely to receive structured reproductive counseling and to pursue preimplantation genetic testing (PGT/PGD), prenatal diagnosis (PND), sex selection, or alternative reproductive strategies. In contrast, individuals without a confirmed genetic diagnosis or with variable penetrance frequently delayed pregnancy and reported significant psychological distress. The third category highlighted an unmet need for counseling despite preserved fertility.
Early results indicate that immunologic disease severity, genetic clarity, and timing of molecular diagnosis, hormonal health, and infection susceptibility significantly influence reproductive outcomes and decision-making in IEI. Multidisciplinary approaches integrating immunology, reproductive medicine, and genetic counseling are essential.
