Although these cases demonstrate the success and the feasibility of the technologies used, we also have to consider some limitations of the PGD/HLA programme.
Firstly, the method is labour-intensive and thus the financial cost is high. On the level of a health care program this aspect must be compared with the probably higher costs related to the use of unrelated donors or a continued program of standard medical treatment (if that is an option) for a number of decades with a no-cure perspective.
Secondly, time is always pressing. In the majority of the cases the transplantation can be postponed for at least one year, but still we need time for the preclinical work, one or more PGD/HLA treatment cycles, and pregnancy.
Thirdly, the clinical success rate of PGD/HLA typing is low. This is a common phenomenon in all centres offering HLA/PGD and couples should be counselled for this because they have put all their hope in this approach to cure their sick child.
An advanced maternal age, as well as a poor ovarian response to hormonal hyperstimulation, are known to have a major impact on the number of the retrievable oocytes and, consequently, on the number of embryos available for analysis, reducing the likelihood of finding transferable embryos. Thus several IVF cycles may be necessary to obtain a pregnancy and a live birth.
The selection of a donor embryo for HSC transplantation before implantation is restricted by the intrinsic genetic constitution of the embryos: only ¼ or 25% (HLA typing), 3/16 or 19% (HLA typing and mutation analysis) is transferable.
The overall number of embryos tested per cycle is low and, consequently, only a part of the patients will have a transfer.