Title: CVS results ... Trans abdominal and transcervical CVS ar
1Amniocentesis and CVS
- Dr. Joseph Har-Toov
- Lis Maternity Hospital
- Tel-Aviv, Israel
2Methods of chromosomal evaluation
- Non invasive
- Fetal cells from maternal blood
- preimplantation embryos (PGD)
- Invasive
- amniotic fluid (amniocentesis)
- placenta (chorionic villus tissue)
- Fetal blood
3Invasive techniques
- Amniocentesis
- Late second trimester after 15 weeks
- Early earlier than 15 weeks
- Chorionic villus sampling (CVS)
- Abdominal
- Trans cervical
- Trans vaginal
- Fetal blood sampling
4karyotype
fish
PCR
5What can be evaluated?
- Chromosomal aberrations
- Trisomy,
- Monosomy,
- Polyploidy,
- Marker chromosome,
- Deletion, duplication, inversion, translocation,
ring chromosome . - Genetic aberrations (DNA)
- Infectious disease
- Biochemical markers (AFP)
6Amniocentesis
- First introduced by Serr and Fuchs and Riis in
the 1950s for fetal sex determination - Only at the late 70th a static ultrasound was
used to locate the placenta and amniotic fluid
pocket - Only In 1983, Jeanty reported a technique of
amniocentesis under ultrasound vision
7Mid Trimester Amniocentesis
- Per coetaneous
- 20-23g needle
- Ultrasound guided
- Usually 20cc amniotic fluid
- Results 2 to 3 weeks
8(No Transcript)
9(No Transcript)
10complications
- Pregnancy loss 0.3-1.0.
- Increase risk
- Needle larger than 18g
- Multiple needle insertion
- Discoloration of the fluid
- High AFP, multiple late abortions, previous
vaginal bleeding - Placental perforation recent studies didnt
find correlation
11Complications
- Leakage of amniotic fluid (better prognosis than
spontaneous leakage) - Amnionitis
- Vaginal bleeding
- Needle puncture of the fetus
- Long term complications
- Respiratory distress??
- Isoimmunization??
12Amniocentesis and HIV positive women
- Increased rate of vertical transmission
- Chemoprophylaxis previous to amniocentesis
appears to be beneficial in preventing vertical
transmission
13Multiple Gestation
- Three methods
- Indigo carmine injection to the first sac
- A single needle puncture sampling technique
(Jeanty 1990) - Simultaneous visualization of two needles on each
side of the separating membrane (Bahado-Singh
1992) - Abortion risk probably higher
- Detailed description of fetus
position and placental location
14Early Amniocentesis 9-14 weeks
- Introduced at late 80th
- 10-14 weeks gestation
- Only the amniotic (inner) sac should be aspirated
- Approximately 1 cc for gestational age
- Higher rate of pregnancy loss, talipes
equinovarus, and post procedural amniotic fluid
leakage - laboratory failure op to 20
15Chorionic villus sampling
- Was developed in the 80th
- percutaneous transabdominal with 19-20g needle
16Chorionic villus sampling
- Was developed in the 80th
- percutaneous transabdominal
- transvaginal
- transcervical
17(No Transcript)
18(No Transcript)
19- 15-30mg each aspiration
- 20mg ideal for cytogenetic testing
- 30-40mg for cytogenetic and other direct
molecular and biochemical tests
20CVS results
- Direct analysis examines the trophoblast cells of
the placenta (very rapidly dividing cells) - Results in few hours
- greater vulnerability to mitotic error
- Cultured analysis examines the fibroblast like
cells of the villus stroma or mesenchymal core. - Approximately 7-10 days
- Accurately reflect the chromosomes of the fetus.
21Risk of invasive procedure
- Early amniocentesis
- High pregnancy loss
- High fetal malformations
- High rate of multiple needle insertions (4.7)
- High rate laboratory failures (1.8)
- Late amniocentesis
- Low pregnancy loss (0.3-1)
- Low rate of multiple needle insertions (1.7)
- Low rate laboratory failures (0.2)
22Risk of invasive procedure - CVS
- Transabdominal CVS as safe as second trimester
amniocentesis - Trans abdominal and transcervical CVS are equally
safe and efficacious, provided that centers have
expertise with both approaches - In approximately 35 of cases, clinical
circumstances will support one approach over the
other - Limb reduction not after 9 weeks
23mosaicism
- True chromosomal mosaicism is when two or more
abnormal cells lines are detected in two or more
culture flasks from the same individual. - Pseudomosaicism is a term used to describe two
abnormal cell lines that are found in only one
culture flask (not reported to the patient)
24mosaicism
- Most often involving trisomic cell and normal
cells - 1-2 of pregnancies undergoing CVS
- 0.1 of pregnancies undergoing amniocentesis
- Clinical outcome of chromosomal mosaicism is
strongly dependent on the specific chromosome
involved and the number of trisomic cells in both
the placenta and the fetus
25Mosaicism (trisomic cells) in CVS
- Option of an additional prenatal diagnostic
procedure (amniocentesis or fetal blood sampling)
26Mosaicism (trisomic cells) in CVS
- Four possible conditions
- Mosaicism only in the placenta not affecting the
fetus or placental function. - Mosaicism only in the placenta not affecting the
fetus but alter placental function (IUGR) - Trisomy cells are both in the placenta and in the
fetus - Trisomy cells in the placenta and uniparental
disomy in the fetus
27Mosaicism (trisomic cells) in amniotic fluid
- Probably there are trisomic cells in the fetus
- The true level and distribution of trisomic cells
cannot be accurately assessed with any prenatal
procedure - Ultrasound is often the best judge of how a baby
is developing
28Uniparental Disomy
- Arises when an individual inherits two copies of
a chromosome pair from one parent and no copy
from the other parent - Maternal UPD two copies from the mother
- Paternal UPD two copies from the father
29How does UPD happen?
- Loss of a chromosome from a trisomic zygote,
"trisomic rescue" - Duplication of a chromosome from a monosomic
zygote, "monosomic rescue" - Fertilization of a gamete with two copies of a
chromosome by a gamete with no copies of the same
chromosome, called gamete complementation.
30Trisomic rescue following an error in meiosis
heterodisomy
31Trisomic rescue followed an error in meiosis II
isodisomy
32UPD - health concerns in people for two possible
reasons
- Parental imprinting in the case of heterodisomy
and isodisomy - Unmasking of recessive conditions in some cases
of isodisomy
33Clinical consequences of UPD
- molecular UPD testing should be considered for
certain chromosomes (including 6, 7, 11, 14, 15)
that are known to have adverse phenotypic
imprinting effects.
34Factors considered when trying to predict the
outcome of mosaicism
- the chromosome involved
- A mosaic finding 18 or 21 is likely to have worse
implications - mosaic finding for trisomy 15 or 16 is likely to
have less implications (trisomy 15 or 16 cells
cannot survive )
35Factors considered when trying to predict the
outcome of mosaicism
- The tissues affected and level of trisomy in
those tissues - The tissue affected cannot be evaluated
- The level of trisomy can be only estimated
36Factors considered when trying to predict the
outcome of mosaicism
- method of ascertainment
- CVS shows that the placenta is affected
- Amniotic fluid suggests that at least one fetal
tissue may be affected - Fetal blood sampling confirms the diagnosis of
chromosomal mosaicism
37Factors considered when trying to predict the
outcome of mosaicism
- ultrasound findings
- presence/absence of uniparental disomy
- number of previous case reports known in the
literature
38Thank you