CFTR mutation screening in an assisted reproductive clinic

Introduction: Cystic fibrosis (CF) is the most common deleterious single-gene recessive disorder in non-Hispanic Caucasians. Mutations within the CF transmembrane receptor (CFTR) gene produce a variable phenotype, including pulmonary disease, pancreatic insufficiency, meconium ileus and infertility. Screening of antenatal/preconception patients to identify CFTR mutation carriers has been shown to reduce the incidence of CF-affected babies at birth. The application of preconception screening to assisted reproductive technology (ART) patients enables carrier couples a choice between prenatal screening and preimplantation genetic diagnosis (PGD).

Aim: To screen patients entering an infertility clinic, for 30 common CFTR mutations, and to detect carrier patients prior to initiating assisted reproductive treatment.

Method: DNA from 5600 infertility patients was screened using a PCR/OLA kit for 30 CFTR mutations. All identified carriers and carrier couples were offered genetic counselling. Prenatal testing and PGD for CFTR mutations were offered to carrier couples where appropriate.

Results: A total of 5600 patients were screened for 30 CFTR mutations with 261 carriers being identified and at a significantly increased carrier rate of one in 21.5 (4.66% ± 0.55%). R117H/c.350G>A was significantly increased in this infertile population and accounted for 13.8% of all mutations identified. Twelve carrier couples were identified, and nine carrier couples had at least one cycle of PGD for CFTR mutations.

Conclusion: The carrier rate of CFTR mutations is elevated in patients presenting for infertility treatment, and preconception screening should be encouraged in all patients entering ART clinics.