Genetic Risks in IVF and ICSI
Jane Fleming, Associate Genetic Counsellor, Brisbane
Infertility is reported to occur in approximately 15% of couples, and chromosomal or genetic causes have been identified in a substantial number of these patients. To circumvent these fertility problems many couples undergo fertility treatments, in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI); however, there are reports of additional genetic risks associated with these procedures. In this presentation, an outline of genetic risks in IVF and ICSI will be explored, including risks associated with infertility, transmission of genetic conditions, limitations of genetic testing or screening and the implications of the ART procedure.
Both male and female factor infertility have been associated with an increased incidence of aneuploidy, structural chromosome rearrangements, or monogenic conditions in subfertile patients. For example, in approximately 25% of cases of azoospermia and severe oligozoospermia in males, infertility is attributable to a sex chromosome aneuploidy, Y chromosome microdeletion, or congenital bilateral absence of the vas deferens – often associated with cystic fibrosis transmembrane receptor gene mutations. In females, sex chromosome abnormalities (mostly mosaic), autosomal structural rearrangements and some genetic conditions can also lead to subfertility. In some of these cases of infertility there is an additional risk of vertical transmission of a chromosomal or genetic condition to ART conceived offspring.
IVF and ICSI are also performed in cases where a genetic condition is known within the family, for couples with recurrent pregnancy loss or implantation failure, or individuals using donor gametes. Pre-implantation genetic diagnosis, pre-implantation genetic screening and prenatal diagnosis are options for those patients at risk of transmitting a genetic condition or chromosomal abnormality to their offspring. However these procedures also have benefits and limitations.
Currently, it is estimated that over three million children worldwide have been conceived using ART. Over this time, there have been reports of increased risks of birth defects, aneuploidy, imprinting errors due to maternal hypomethylation, and possible childhood cancers in offspring conceived through IVF and ICSI. Although these risks appear to be low, research in this area is continuing and currently it is unclear whether these risks might be associated with the causes of parental subfertility or the ART procedure.
In cases where fertility treatment is being considered and there is a genetic risk for offspring, regulatory bodies recommend that couples or individuals receive genetic counselling, to provide information about the diagnosis, to discuss risks to offspring and other family members, to review reproductive options available, and any psychosocial or emotional needs of the couple. Therefore, the implications of genetic risk in IVF and ICSI will also be explored from a genetic counselling perspective.
