Preimplantation Genetic Diagnosis
Because only unaffected embryos are transferred to the uterus for implantation, preimplantation genetic testing provides an alternative to current postconception diagnostic procedures (ie, amniocentesis or chorionic villus sampling), which are frequently followed by the difficult decision of pregnancy termination if results are unfavorable. PGD and PGS are presently the only options available for avoiding a high risk of having a child affected with a genetic disease prior to implantation. It is an attractive means of preventing heritable genetic disease, thereby eliminating the dilemma of pregnancy termination following unfavorable prenatal diagnosis.
Indications for Preimplantation Genetic Diagnosis:
Primary candidates for PGD, These include the following:
Conditions diagnosed using PGD
Sex-Linked Disorders
Single gene defects
Although progress has been made, some single gene defects, such as cystic fibrosis, have multiple known mutations. In cystic fibrosis, only 25 mutations are currently routinely tested.
Because most of these rare mutations are not routinely tested, a parent without any clinical manifestations of cystic fibrosis could still be a carrier.
This allows the possibility for a parent carrying a rare mutation gene to be tested as negative but still have the ability to pass on the mutant cystic fibrosis gene.PGD can also be used to identify genetic mutations like BRCA -1, which does not cause a specific disease but increases the risk of a set of diseases.
Chromosomal Disorders:
Indications for Preimplantation Genetic Screening
Primary candidates for PGS can include the following:
- Women of advanced maternal age
- Couples with history of recurrent pregnancy loss
- Couples with repeated IVF failure
- Male partner with severe male factor infertility
These patient populations are at risk of failure with IVF because of a high proportion of aneuploid embryos. PGD is believed to decrease this risk by selecting chromosomally normal embryos that have a higher chance of implantation.Advanced Maternal Age:
The risk of aneuploidy in children increases as women age. The chromosomes in the egg are less likely to divide properly, leading to an extra or missing chromosome in the embryo (see Table 1). The rate of aneuploidy in embryos is greater than 20% in mothers aged 35-39 years and is nearly 40% in mothers aged 40 years or older. The rate of aneuploidy in children is 0.6-1.4% in mothers aged 35-39 years and is 1.6-10% in mothers older than 40 years.
- The difference in percentages between affected embryos and live births is due to the fact that an embryo with aneuploidy is less likely to be carried to term and will most likely be miscarried, some even before pregnancy is suspected or confirmed.
- The difference in percentages between affected embryos and live births is due to the fact that an embryo with aneuploidy is less likely to be carried to term and will most likely be miscarried, some even before pregnancy is suspected or confirmed.
- Therefore, using PGD to determine the chromosomal constitution of embryos increases the chance of a healthy pregnancy and reduces the number of pregnancy losses and affected offspring.One of the most frequent aneuploidies, trisomy (ie, 3 identical chromosomes present in the embryo), is trisomy of chromosome 21, which leads to Down syndrome.
- This particular abnormality also frequently leads to spontaneous miscarriage, the precise frequency of which is difficult to determine.
- Thus, the only reliable information is on the frequency of babies born with Down syndrome. An informative article in the Journal of the American Medical Association [4] includes information on estimating the incidence of trisomy 21/Down syndrome in fetuses at 16 weeks of pregnancy (also see Table 2).
- Recurrent pregnancy loss (RPL) is usually defined as 2 or more consecutive pregnancy losses before 20 weeks’ gestation.
- The cause is frequently unknown but may be secondary to fetal anomalies or uterine abnormalities. Chromosomal abnormalities are noted in 50-80% of abortuses,[8] and couples with RPL have a higher percentage of aneuploid embryos than patients without RPL.[9] However, the use of PGS does not improve the pregnancy rate in this group of patients but increases the likelihood of delivery at term.[10] PGS also benefits the subgroup of patients who have proven abnormal concepti by cytogenetic analysis.[10]