Can In Vitro Fertilization (IVF) prevent the occurrence of Down syndrome in a baby?

From the Guidelines

IVF combined with preimplantation genetic testing (PGT) can significantly reduce the risk of having a baby with Down syndrome, but it cannot provide a 100% guarantee. During IVF, embryos can be screened for chromosomal abnormalities, including the extra chromosome 21 that causes Down syndrome, before being transferred to the uterus. This process, called PGT-A (preimplantation genetic testing for aneuploidy), allows doctors to select embryos without the extra chromosome for implantation. The testing involves removing a few cells from each embryo at the blastocyst stage (day 5-7) and analyzing their chromosomal makeup. While highly accurate (95-98%), PGT has limitations including the possibility of mosaicism (where some cells have different chromosomal arrangements than others), sampling errors, or technical limitations, as discussed in the recent study by 1.

Key Considerations

• The implementation of PGT-P has been challenged by several groups of scientists and professional societies, including the American Society of Human Genetics, the European Society of Human Genetics and the European Society of Human Reproduction and Embryology, all of which have called the utilization of PGT-P unethical and reject its use in clinical care, as mentioned in 1 and 1.
• IVF with PGT is expensive, typically costing $20,000-$30,000 per cycle including the genetic testing, and may not be covered by insurance.
• The process also requires hormone stimulation, egg retrieval, laboratory fertilization, and embryo transfer, with success rates varying based on maternal age and other factors.
• For those concerned about Down syndrome, genetic counseling before conception is recommended to understand all available options, as the use of PGT-P has not been proven to provide clinical utility, according to 1.

Limitations and Risks

• PGT has limitations including the possibility of mosaicism, sampling errors, or technical limitations.
• The range of PRSs between the embryos from the same biological parents is lower than the wider range of risk for individuals in the general population, as discussed in 1.
• Environmental factors play a role in the development of polygenic conditions or traits, which may limit the effectiveness of PGT-P.
• The lack of inclusivity is significant to consider because the genome-wide association studies that PGT-P is based on mainly use data from people of European ancestry, making PGT-P less effective for those with non-European ancestries, as mentioned in 1.

From the Research

In Vitro Fertilization (IVF) and Down Syndrome Prevention

• IVF itself does not prevent the occurrence of Down syndrome in a baby, but preimplantation genetic screening (PGS) can be used to screen embryos for chromosomal abnormalities, including Down syndrome, before implantation 2.
• PGS has been suggested as an alternative to prenatal testing for Down syndrome, and most women favor PGS for Down syndrome screening, even if it is not 100% sensitive 2.
• However, the acceptability of PGS depends on its effect on pregnancy chances and its sensitivity to detect Down syndrome embryos 2.

Prenatal Screening and Diagnosis

• Prenatal screening and diagnosis of chromosomal abnormalities, including Down syndrome, are complicated in IVF pregnancies due to higher maternal age, multiple pregnancy rate, and increased risk of chromosomal abnormalities 3.
• First-trimester prenatal screening based on maternal age, nuchal translucency scan, and biomarkers is appropriate for IVF/ICSI singletons, but biomarkers may be altered, causing a higher false-positive rate 3.
• Correction factors have been developed to adjust for the mode of conception in risk calculations for Down syndrome in singleton pregnancies 3.

Impact of Noninvasive Prenatal Testing (NIPT)

• The implementation of NIPT has raised questions about its impact on termination of pregnancy and live birth rates of infants with Down syndrome 4, 5.
• Studies have shown that termination rates following NIPT are unchanged or decreased compared to historical termination rates, and the impact on live birth rates may be minimal in settings where termination rates fall 4, 5.
• NIPT has rapidly gained global acceptance, but population uptake is influenced by healthcare structures, historical screening practices, and cultural factors 5.

Serum Markers and Down Syndrome Screening

• Serum marker levels, including alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin, may be altered in IVF pregnancies, which can affect Down syndrome screening results 6.
• The screen positive rate in IVF pregnancies may be higher than in non-IVF pregnancies due to these alterations, and adjustment of serum marker values may be necessary to avoid false positives 6.