PGT and Prenatal Genetics
PGT and Prenatal Genetics
PGT and Prenatal Genetics
1. Stimulation phase
2. Egg retrieval
3. Collect sperm
4. In vitro fertilization
(Genetic Testing)
5. Embryo Transfer
6. Implantation
THREE TYPES OF PRE- IMPLANTATION GENETIC TESTING
PGT-A
(ANEUPLOIDY SCREENING)
• PGT-A detects aneuploidy among IVF embryos Aneuploidy exists across all ages and
increases with maternal age.
• Chromosomal aneuploidy is known to be a major cause of IVF failure.
ARRAY
Automated array technology
Detect 23 pairs of chromosome
NGS
Latest technology
Detect 23 pairs of chromosome
High-throughput
Easier experimental operation
PGT-SR
(STRUCTURAL REARRANGEMENTS)
• PGT-SR, preimplantation genetic testing for structural chromosomal rearrangements, is
a genetic test performed on embryos created through IVF to screen for chromosomal
structural rearrangements normally caused by balanced translocations and inversions.
• In humans, the most common aneuploidies are trisomies, which represent about
0.3% of all live births. Trisomies are characterized by the presence of one
additional chromosome, bringing the total chromosome number to 47.
• With few exceptions, trisomies do not appear to be compatible with life. In fact,
trisomies represent about 35% of spontaneous abortions
Science of identifying structural and/or functional
abnormalities-birth defects in the fetus
US Biochemical Karyotyping
MRI cffDNA Chromosomal DNA
NON- INVASIVE PRENATAL TESTING (NIPT)
NON- INVASIVE PRENATAL TESTING (NIPT)
NIPT to the rescue
• Singleton Pregnancy - test can be performed any time after 10 weeks within the first
trimester.
• Twin Pregnancy - test can be performed any time after 12 weeks within the first
trimester.
• On the basis of available data, detection rates appear to be higher.
• There is a high negative predictive value for Down syndrome. This may be important
for patients seeking to avoid the risks (e.g., fetal loss) inherent with invasive testing.
• NIPT has a lower false-positive rate, meaning fewer women will receive a “positive”
screen, necessitating fewer invasive procedures.
• Risk assessment is less dependent on gestational age
What NIPT is not – Points to remember
“The American College of Obstetricians and Gynecology recommends offering carrier screening to all pregnant women or
couples considering pregnancy”
Couple Carrier Screening:
WHY And WHO
Couples who:
● Carriers are typically healthy and do not have ● are currently pregnant or planning a
symptoms. pregnancy
● Most of us are carriers of at least one genetic ● have a family history of a genetic disorder
condition. ● would like additional information about the
● For most diseases, both partners have to be reproductive risks of having a child with a
carriers for the same condition for the child genetic disorder
children to be at increased risk ● are planning to donate eggs, sperm, or
● Each individual harbours an average of 2.8 embryos
known severe recessive mutations.# ● belong to a high-risk ethnic group
● have a consanguineous partner
CASE STUDY 1
• Couple married non- consanguineously was currently pregnant with gestational age
of 22 weeks+ 05 days. The fetus ultrasound scan reports indicated
polyhydramnios, and club foot appearance.
• No family history
CASE STUDY 1
The couple married non- consanguineously for 7 years presented with history of 2
MTPs:
A complete three-generation family history was obtained. Husband is first born to a non- consanguineous
parents. He has 2 brothers and 1 sister. Wife has 2 sisters and 4 brothers. There is no history of cancer in
the family. Following is the pedigree based on family history reported:
CASE STUDY 2
• Likely compound heterozygous variant in PKHD1 gene associated with Polycystic kidney disease 4 with
or without polycystic liver disease (263200). The variant c.5751G>Ap.Gln1917Gln was identified in Exon
35 and was classified as Uncertain Significance.
• Another variant, c.982C>Tp.Arg328* was identified in Exon 14 and classified as Pathogenic. This
disorder is inherited in Autosomal Recessive manner.
• The couple was counseled about the condition associated with the disorder.
• Sanger validation of identified variants in the parents recommended.
CASE STUDY 3
• Couple married non- consanguineously presented with history of two neonatal deaths (male child).
• Genetic testing was done for second child and a variant of Uncertain significance was identified in G6PD
gene variant c.961G>A (p.Val32Met) on exon 9 in hemizygous state corresponding to G6PD deficiency.
• Presently, the wife is diagnosed to have polycystic ovarian disease and she is under treatment for the
same.
• The couple was counseled about the disorder and explained testing options which included parental
sanger analysis, Couple Clinical Exome Sequencing and Couple Whole Exome Sequencing.
• The patient opted for Couple Whole Exome Sequencing.
CASE STUDY 3
PEDIGREE:
CASE STUDY 3
• Couple Whole Exome Sequencing report showed carrier for pathogenic variant in the wife for G6PD
deficiency. The husband’s report was negative.
CASE STUDY 3
• The couple was explained about the Whole Exome Sequencing report.
Husband Wife
• Couple presented with Bad obstetric history (BOH) and having a history of two neonatal death.
• In their first pregnancy (G1), there is history of neonatal death of a male child at 28th day of life with
congenital anomalies.
• In their second pregnancy (G2), there is history of neonatal death of a male child at first few months of
life due to clinically suspected Hemophagocytic Lymphohistiocytosis (HLH).
CASE STUDY 5
• After detailed genetic counseling, Pre-PGT-M opted for both the variants. Father’s
mutation c.658G>C (p.Gly220Arg) in the exon 3 of the PRF1 gene and Mother’s
mutation c.386G>C (p.Trp129Ser) in the exon 2 of the PRF1 gene causative of
autosomal recessive Familial hemophagocytic lymphohistiocytosis 2.
CASE STUDY 5
• Based on Pre-PGT-M report, PGT-M was offered to the couple to screen embryos for the mentioned two
variants causative of Autosomal recessive Familial hemophagocytic lymphohistiocytosis 2.