The Contribution of Cystic Fibrosis Mutations to Male Infertility

Project Description

Funding RCSI Rotunda IVF Programme Research Funds.
Principal Investigator Dr Edgar Mocanu (MD Project).
Researchers Caroline Joyce MSc, Dr Tom Barrett.
Collaborators Professor Robert Harrison, Rotunda Hospital and RCSI.


Male infertility as a result of congenital absence of the vas deferens (CAVD) is a recognised complication of cystic fibrosis (CF).

However, it has been reported that CF mutations are also present at higher than expected frequency in infertile men without CAVD.

We have studied 244 males without CAVD who presented with azoospermia or oligospermia (<20 million sperm/ml) at a Dublin infertility clinic. Eight males with an abnormal karyotype and 4 with Yq microdeletions were excluded.

We analysed lymphocyte DNA for 8 cystic fibrosis mutations: F508, R117H, I507, G542X, G551D, R560T/R560K, R352Q, and 621+1GT.

Eighteen mutation carriers were identified in the 232 males tested (7.8%), significantly higher than the CF carrier frequency in the Irish population (5%; p=0.035). Sixteen men carried the F508 mutation, one carried G551D, and one carried the 621+1G?T mutation. All of these mutations would be expected to result in a marked reduction of the amount of CFTR expressed.

We have also tested for the ‘5T’ variant in intron 8 of the CFTR gene, as it is known to be associated with reduced CFTR expression. We found 35 of our 232 men (15.1%) to have the 5T variant (expected 5%, p><<0.001). The excess of 5T alleles was highly significant in men with 1-5 million sperm/ml, and in men with 5-20 million sperm/ml, but less significant in men with very low sperm counts or azoospermia.

Only one CF mutation carrier and two 5T variant carriers had azoospermia, indicating that undiagnosed CBAVD is not likely to be the explanation for our results.


  1. Cystic fibrosis mutations and variants associated with male infertility.
    Barton D.E, Joyce C, Barrett T, Harrison R.
    Journal of Medical Genetics 1998 35(Supp. 1): S86.