Genetic risks associated with advanced assisted reproductive technology: TRANSMISSION OF EXISTING GENETIC ABNORMALITIES THROUGH ASSISTED REPRODUCTION (Part 2)

There are currently more than 1000 known mutations in the CFTR gene, the most common one being delta-F508 mutation, appearing in about 75% of people affected with cystic fibrosis in North America. Men with CBAVD should be screened for CFTR mutation, because 50% to 80% of them are carriers of at least one known CFTR gene mutation, while around 10% have two. In addition, the female partner should also be screened for CFTR mutation, although the likelihood of detecting a mutation depends on the woman’s ethnic background. Screening is generally performed for as least the most common 25 mutations (Table 1). When counselling these couples, it should be emphasized that even in the absence of a detectable mutation from a screening test, there may still be a risk of cystic fibrosis or related phenotype, because less common mutations that are not in the screening test panel may be present. buy asthma inhalers
Men with nonmosaic Klinefelter’s syndrome may achieve pregnancy with ICSI. The overall success in testicular sperm retrieval in the literature is about 56%, similar to the success rate in other nonobstructive azoospermic men. Over 11 pregnancies with more than 16 healthy neonates have been reported following ICSI with spermatozoa from men with nonmosaic Klinefelter’s syndrome. Interestingly, sperm of nonmosaic men with Klinefelter’s syndrome (with 47 XXY) rarely display hyperhaploidy (eg, disomy 24 XY or 24 XX). In fact, approximately 1% to 3.4% of these sperm are 24 XY, a rate that is higher than that in infertile (1%) and fertile men (0.2%) but is significantly lower than the theoretical 25% to 50%. In addition to proper genetic counselling, preimplantation genetic diagnosis on embryos should be used to avoid sex chromosomal and autosomal aneuploidy and embryo abnormalities, which are demonstrated to occur at increased rates in men with Klinefelter’s syndrome.

TABLE 1  Common cystic fibrosis transmembrane regulator mutations for carrier screening

AF508 Dl507 G542X G551D W1282X
N1303K R553X 621+1G^T 1717-1G^A A455E
R560T R1162X G85E R334W R347P
711+1G^T 1898+1G^A 2184delA 1078delT 3849+10kbc^T
2789+5G^A 3659delC l148T 3120+1G^A R117H

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