Impact of female CFTR variant carrier status on reproductive outcomes.

OBJECTIVE

This study aimed to investigate the impact of carrying a single pathogenic or likely pathogenic CFTR variant on reproductive outcomes in women undergoing assisted reproductive technology (ART).

METHODS

In this single-center retrospective study, 4479 vitro fertilization (IVF) /intracytoplasmic sperm injection (ICSI) cycles from 3398 patients who had undergone expanded carrier screening (ECS) between January 2022 and November 2024 were analyzed. Cycles were categorized into a control group (n = 4089 cycles) and a CF carrier group (n = 390 cycles) based on the presence of a pathogenic/likely pathogenic CFTR variant in the female partner. The CF carrier group was propensity-score matched to controls at a 1:4 ratio. Subgroup analysis was stratified by variant loci (5T allele or non-5T variants).

RESULTS

Compared with controls, female CF carriers showed lower baseline FSH levels (6.7 ± 2.9 vs. 7.8 ± 4.3, p < 0.05) and a reduced mature oocyte rate (78.4%vs. 84.1%, p < 0.05). In single blastocyst transfer cycles, clinical outcomes were comparable between 5T allele carriers and the control group. Carriers of non-5T CFTR variants had significantly lower clinical pregnancy (34.1%vs. 57.3%, p < 0.05) and live birth rates (25.0%vs. 44.7%, p < 0.05). No significant between-group differences were observed in other ovarian reserve parameters and embryo development.

CONCLUSION

Women carrying a single pathogenic or likely pathogenic CFTR variant (excluding the 5T allele) may exhibit reduced fertility potential and poorer ART outcomes. These results support recommending that women be informed of the possible reproductive implications of CFTR carrier status prior to ART treatment.