Amniocentesis and Chorionic Villus Sampling (CVS)

1. Comparison at a glance

A. Amniocentesis

Definition

Timing

• Genetic amniocentesis: 15-20 weeks, usually after 15 completed weeks.
• May be performed later when indicated.
• Early amniocentesis, at 10-14 weeks, should be avoided because of increased fetal loss, fluid leakage, and talipes equinovarus.

Procedure

1. Pre-procedure counseling and written informed consent.
2. Review blood group, antibody status, infection risks, indications, and desired test.
3. Ultrasound to confirm:
   • Fetal viability
   • Gestational age
   • Number of fetuses
   • Placental location
   • Cord insertion
   • A safe pocket of liquor
4. Under aseptic precautions and continuous ultrasound, a fine needle is passed transabdominally into an amniotic-fluid pocket away from fetus and cord.
5. About 10-20 mL fluid is withdrawn, depending on gestation and laboratory requirement.
6. Check fetal cardiac activity after the procedure.
7. Give anti-D immunoglobulin to an unsensitized RhD-negative mother, according to local protocol.

Indications

Genetic indications

• High-risk aneuploidy screen: positive serum screening, increased nuchal translucency, or high-risk cell-free DNA result.
• Fetal structural anomaly or multiple soft markers on ultrasound.
• Previous child or pregnancy with chromosomal/genetic disorder.
• Parental balanced chromosomal rearrangement.
• Known parental carrier status for a single-gene disease, for example thalassemia, spinal muscular atrophy, cystic fibrosis, or metabolic disease.
• Maternal request after informed genetic counseling.

Non-genetic indications

• Evaluation of suspected fetal infection, in selected circumstances.
• Assessment of fetal anemia by amniotic-fluid bilirubin in selected settings, although Doppler has largely replaced this.
• Assessment of intra-amniotic infection/inflammation in selected cases.
• Therapeutic amnioreduction in severe polyhydramnios, which is distinct from diagnostic amniocentesis.

Tests possible on amniotic fluid

• Rapid aneuploidy detection: QF-PCR or FISH for chromosomes 13, 18, 21, X, and Y.
• Karyotype.
• Chromosomal microarray.
• Targeted gene testing, gene panels, or sequencing when indicated.
• Enzyme assays/metabolite studies for selected inherited metabolic disorders.
• Amniotic-fluid AFP and acetylcholinesterase for open neural tube defects, though high-quality ultrasound has reduced routine reliance on these tests.
• Microbial PCR/culture where clinically indicated.

Complications

• Pregnancy loss: small, procedure-related risk.
• Vaginal spotting or bleeding.
• Transient amniotic-fluid leakage.
• Uterine cramps.
• Chorioamnionitis, very rare.
• Needle injury to fetus or cord, now rare with continuous ultrasound.
• Fetomaternal hemorrhage and Rh sensitization.
• Failed culture, maternal-cell contamination, or inconclusive result.

B. Chorionic Villus Sampling

Definition

Timing

• 11+0 to 13+6 weeks.
• Do not perform before 11 weeks.

Routes

1. Transabdominal CVS

• Most commonly used.
• A needle is passed through the maternal abdomen into the placenta under ultrasound guidance.
• Villous tissue is aspirated.

2. Transcervical CVS

• A catheter is passed through the cervix to the placenta under ultrasound guidance.
• May be used depending on placental location and operator expertise.

Indications

• Positive first-trimester aneuploidy screen or high-risk cell-free DNA.
• Increased NT or early structural anomaly.
• Previous child with genetic disease.
• Known carrier couple for a monogenic disorder.
• One parent with chromosomal rearrangement.
• Need for early fetal sex determination for X-linked disease.
• Maternal request after counseling.

Tests possible on CVS

• QF-PCR/FISH.
• Karyotype.
• Chromosomal microarray.
• Targeted molecular testing for single-gene disorders.
• DNA-based prenatal diagnosis for familial mutations.

Limitations of CVS

1. Cannot directly diagnose open neural tube defects by amniotic-fluid AFP/acetylcholinesterase estimation. A targeted second-trimester anomaly scan remains important.
2. Confined placental mosaicism: the placenta may be chromosomally abnormal while the fetus is normal, or less commonly vice versa.
3. An abnormal or mosaic CVS result may need confirmation by amniocentesis.
4. Maternal-cell contamination can occur.

C. Key counseling points

• It is a diagnostic test, not a screening test, but it does not rule out every congenital anomaly or every genetic disease.
• The exact disorder being tested for and whether the planned laboratory method can detect it.
• Turnaround time:
  • Rapid aneuploidy test: often a few days.
  • Karyotype/culture or microarray: longer.
  • Targeted molecular studies: laboratory dependent.
• Small miscarriage risk and other procedural complications.
• Possibility of failed culture or uncertain findings, such as variants of uncertain significance on microarray.
• CVS-specific possibility of placental mosaicism and need for confirmatory amniocentesis.
• Available options should a fetal abnormality be identified.
• Testing is voluntary: a patient may accept or decline screening or invasive diagnosis. ACOG states that this choice should be discussed with every pregnant patient.

D. CVS versus amniocentesis: exam answer

• Diagnosis is needed in the first trimester.
• There is a known familial mutation requiring early targeted testing.
• Early confirmation after a high-risk first-trimester screen is preferred.

• Gestation is 15 weeks or more.
• Open neural tube defect evaluation is required.
• CVS has shown mosaicism or an equivocal result.
• Placental access for CVS is unfavorable.

E. High-yield viva points

1. CVS gives earlier results but cannot assess open neural tube defects.
2. Amniocentesis is done after 15 weeks.
3. CVS is done at 11-13+6 weeks and never before 11 weeks.
4. Both procedures are ultrasound guided and carry a small procedure-related loss risk.
5. CVS samples placenta, so confined placental mosaicism can produce discordant results.
6. An abnormal/mosaic CVS result may require confirmation by amniocentesis.
7. Give anti-D prophylaxis to eligible unsensitized RhD-negative mothers after an invasive procedure.
8. Cell-free DNA is a highly accurate screening test, not a diagnostic replacement for CVS or amniocentesis.

One-line conclusion