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GROUP WORK 3:
There are several types of Genetic Testing and Screening. What is
Noninvasive Prenatal Screening (NIPS) and What is Preimplantation Genetic
diagnosis (PGD)? Please describe the methods, indications, and applications of
NIPS and PGD.
Noninvasive Prenatal Screening (NIPS)
-NIPS or NIPT (noninvasive prenatal testing) is a method of determining the risk that the fetus
will be born with certain genetic abnormalities. This testing analyzes small fragments of cell-
free DNA (cfDNA) that are circulating in a pregnant woman’s blood. 1

Figure 1. cfDNA are circulating in a pregnant woman’s blood, YM, Lo et al. 1997, ‘Presence of fetal DNA in
maternal plasma and serum’, The Lancet, 350;485-487

-Method:

+ NIPS analyzes cell-free DNA from a maternal blood sample (mixture of fetal and maternal
DNA) to screen for common chromosomal conditions.
+ The NIPS workflow consists of several steps. A typical workflow starts with isolating plasma
from maternal blood draw. Cell-free DNA (cfDNA) is then extracted from plasma and prepared
for analysis.2

1
https://medlineplus.gov/genetics/understanding/testing/nipt/ What is noninvasive prenatal testing (NIPT) and
what disorders can it screen for? 28 July 2021.
2
https://www.illumina.com/clinical/reproductive-genetic-health/nipt.html Martin Chavez, NIPT: A Breakthrough
Genomic Solution
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Figure 2. Sequencing of Circulating Cell-free DNA during Pregnancy DW, Bianchi et al. 2018, N Engl J Med,
379:464-473

+ However, because NIPT analyzes the cf-DNA of both mother and fetus, false positives can
occur in some cases:3
-Mosaic in fetus or mother
-The abnormalities only appear on the placenta, the fetus is still normal
-The mother has a chromosomal abnormality or has cancer
-Indications:
+ Cell-free DNA-based NIPT has been validated as a screening test for certain fetal aneuploidy in
high-risk women. High-risk indications include advanced maternal age (AMA), positive serum
screen result, abnormal fetal ultrasound findings, and a previous affected pregnancy 4
+ NIPT is most often used to look for chromosomal disorders that are caused by the presence of
an extra or missing copy (aneuploidy) of a chromosome.
-Application:
+ The application of expanded noninvasive prenatal screening for genome-wide chromosomal
abnormalities and genetic counseling
+ NIPT primarily looks for Down syndrome (trisomy 21, caused by an extra chromosome
21), trisomy 18 (caused by an extra chromosome 18), trisomy 13 (caused by an

3
 Renga, B. (2018). Noninvasive European Journal of Obstetrics & Gynecology and Reproductive Biology, 225, 5-8.
4
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4563409/ Lindsay Fosler, Noninvasive prenatal testing (NIPT):
differences in testing indications between the US and Southeast, Asia Ann Transl Med. 2015 Sep; 3(Suppl 2):
AB109.
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extra chromosome 13), and extra or missing copies of the X chromosome and Y

chromosome (the sex chromosomes). The accuracy of the test varies by disorder 5
Preimplantation Genetic diagnosis (PGD)
-Preimplantation genetic diagnosis (PGD) involves the genetic testing of biopsy material from
embryos that are generated through in vitro fertilization (IVF) techniques and involves the
transfer of chromosomally normal and disease-free embryos to the uterus.

Figure 3. How PGD performed step by step, Amel Khelifi Schreiber et al, 2020.

-Method
The typical treatment cycle for PGD6:
Step 1: Stimulation of the ovaries
In order to create embryos for genetic testing, the ovaries must be artificially stimulated using
hormones to produce several eggs at the same time.
Step 2: Collection of eggs from the ovaries
At the appropriate time, the eggs are removed in during a surgical procedure known as egg
retrieval. Once the eggs are removed, they are inspected to determine which are mature and
normal appearing.
Step 3: Insemination/injection of sperm
Fertilization during PGD will be done either by:

5
https://medlineplus.gov/genetics/understanding/testing/nipt/ What is noninvasive prenatal testing (NIPT) and
what disorders can it screen for? July 28, 2021
6
https://geneticalliance.org.uk/information/service-and-testing/preimplantation-genetic-diagnosis-how-does-it-
work/ PREIMPLANTATION GENETIC DIAGNOSIS: HOW DOES IT WORK? September 1, 2016.
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-In Vitro Fertilization (IVF): Sperm and eggs are placed together in a culture dish to allow
fertilization to occur.
-Intracytoplasmic Sperm Injection (ICSI): A single sperm is injected in the center of an egg. This
technique is used for conditions caused by a single faulty gene.
The morning after injection/insemination of the sperm, the embryologist carefully examines
each egg to see if fertilization has occurred.
Step 4: Embryo biopsy
-The eggs that were successfully fertilized are grown in the laboratory for 5-6 days when the
embryo forms what is called a blastocyst of about 100-150 cells. At this stage trophectoderm
biopsy (the cells which will form the placenta) takes place.
Step 6: Embryo Testing
The cells are tested to see if the embryo from which they were removed contains the
abnormality that causes the genetic condition.
Step 7: Embryo Transfer
Only those embryos that do not have the specific genetic condition that was tested for will be
transplanted into the woman’s uterus. Usually, one embryo will be transferred to the uterus at
any one time to avoid the possibility of multiple births (more than one baby in a pregnancy).
Step 8: Pregnancy Test
Twelve days after the embryo transfer, the woman is given a pregnancy test. A positive
pregnancy test means that an embryo has implanted.
-Indication:
Preimplantation genetic diagnosis (PGD) refers specifically to when one or both genetic parents
have a known genetic abnormality
-Application:
Preimplantation genetic diagnosis can be offered for three major categories of disease. Firstly,
it can be used to determine the sex of the embryo for sex linked disorders. Secondly, it can be
used to identify single gene defects such as cystic fibrosis. Thirdly, it can be used in
chromosomal disorders.7

7
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1120169/ Frances A Flinter
Preimplantation genetic diagnosis