IVF with ovocyte donor

Question

We intend to proceed within the next few months to IVF with ovocyte donation.
My husband was tested for 50 basic CF mutations and was found concerning the intron 8-5T/7T/9T to be a carrier of 5T/9T polymorphic tracts. The results for the other subtypes were normal (for the subtype R117H in particular).
Should mu husband be tested for more CF mutations? The doctor does not consider it to be necessary for the ovocyte donor to be tested for CF. Is this true? Is there a chance I could have a child with CF?

Answer

Dear friend,
You intend within the next few months to proceed to an IVF with an ovocyte donation and your husband was tested for 50 mutations and was found to be a carrier of a 5T polymorphic tract.
Yes, I do believe that your husband must be tested for the greatest possible number of CF mutations, in order to minimize (and almost eliminate) the possibility of a child with CF.
As you probably know, CF only occurs in a child, if it inherits one CF-causing mutation from the father and one from the mother. If the child inherits only one mutation from one parent, it is healthy (healthy carrier of one CF-causing mutation).

Therefore, if the father has undergone an extensive genetic investigation and no other CFTR mutations are found (please note, there is no genetic test that can 100% exclude CF-causing mutations) besides the mentioned 5T allele, there is a 50% chance that he gives the 5T allele to the unborn child. The untested mother (ovocyte donor) has a risk of 1:25 to carry a CF-causing mutation that she could give with a chance of 50% to the unborn child. If both mutations would come together, the child will not (!!) suffer from the classical form of CF, but it has to be mentioned, that the clinical picture will be determined by the less severe mutation, and this would be then the 5T allele. Therefore the child could in this specific case develop a so-called CFTR-related disorder with sterility problems later in life if it is a male child or chronic pancreatitis.

If the extendend genetic testing of the father would reveal another CFTR mutation, that could cause CF, a genetic testing of the ovocyte donor would be recommended in anyway in order to calculate the risk.
Therefore, the decision, if the ovocyte donor should also be tested for CFTR mutations even if the father comes out to carry only a 5T allel, remains an individual decision, as the risk to have a child with classical CF can then be excluded to great extent, however a mild CFTR-related disorder could occur in the child with the chance of 1/100 (1/2 x 1/25 x 1/2), and this could be of course minimized if the ovocyte donor would also be tested. A genetic counselling would be helpful here.

Friendly,
Dr. Stavros Doudounakis and Dr. Daniela d'Alquen

10.01.2015