Invasive prenatal testing (amnio/CVS)
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Invasive prenatal testing, chorionic villus sampling (CVS) and amniocentesis, obtains fetal cells for direct diagnostic genetic analysis. Unlike screening tests (including NIPS), invasive testing is diagnostic: a positive result indicates the fetus is affected (within the analytic sensitivity of the assay). Procedures carry a small but real risk of pregnancy loss.
- Timing: 10–13 weeks' gestation (earlier than amnio; allows earlier decision-making).
- Source: chorionic villi, placental tissue of trophoblastic origin.
- Approach: transcervical (11–13 wks) or transabdominal (both are comparable in experienced hands).
- Procedure-related loss rate: about 1 in 300–500 when performed by experienced operators.
- Not recommended before 10 weeks due to historical association with limb reduction defects.
- Timing: 15 weeks onward (early amnio <15 wks is associated with higher loss and talipes, now avoided).
- Source: amniotic fluid, which contains fetal cells (amniocytes) derived from fetal skin, GU tract, and respiratory shedding.
- Approach: transabdominal needle aspiration under continuous ultrasound guidance. 20 mL typically obtained.
- Procedure-related loss rate: about 1 in 500–1000 in experienced centers. Meta-analyses of contemporary practice suggest rates may be lower than historical 1/200 estimates.
- Other uses: amniotic fluid alpha-fetoprotein + acetylcholinesterase for open NTDs; fluid biochemistry for certain metabolic conditions; fluid culture for infections.
- Karyotype (FISH for rapid aneuploidy first): detects numerical aneuploidies and structural rearrangements >5–10 Mb. 7–14 days for final report.
- Chromosomal microarray (CMA): detects submicroscopic copy-number variants (pathogenic microdeletions/microduplications). ACOG/SMFM recommend CMA over karyotype for fetal structural anomalies.
- NGS / exome sequencing: offered when CMA is normal but fetal anomalies persist. Diagnostic yield about 10% additional in anomalous pregnancies.
- Single-gene testing: targeted to familial variants (PGT carryover, known carriers).
- Biochemical and infectious assays: indicated per clinical context.
| Feature | CVS | Amniocentesis |
|---|---|---|
| Gestational age | 10–13 weeks | 15+ weeks |
| Tissue | Placental (trophoblast) | Fetal (amniocytes) |
| Procedure loss rate | 1 in 300–500 | 1 in 500–1000 |
| Confined placental mosaicism | 1–2% | <1% |
| AFP / NTD detection | No | Yes |
| Single-cell biochemistry | Limited | Broader |
- Mosaicism restricted to the placenta, not the fetus. Found in about 1–2% of CVS samples.
- Often causes discrepancies between CVS and fetal karyotype. Follow-up amnio is recommended when CPM is suspected.
- Uniparental disomy (UPD) rescue of a trisomic conception can leave confined placental trisomy with a UPD fetus: important for chromosomes 6, 7, 11, 14, 15, 20 (imprinted regions).
- Diagnostic vs screening: NIPS screens; CVS/amnio diagnose. Positive NIPS → offer invasive testing before decisions.
- Discuss loss risk in context: current procedure-related loss is small (often <0.3%) relative to background miscarriage risk in early pregnancy, but it is real and non-zero.
- Rh-negative patients should receive anti-D immunoglobulin (RhoGAM) after invasive procedures.
- Twin gestations: both sacs must be sampled for amnio (di/di requires two separate taps; mono/di shares amnion but may have discordant karyotypes, especially in TTTS).
- CVS at 10–13 weeks; amnio at 15+ weeks. Avoid earlier amnio (<15 wks) due to talipes/loss risk.
- CVS samples placenta; amnio samples fetus. This is the mechanistic basis for CPM rates differing between them.
- CMA is first-tier for fetal structural anomalies; karyotype remains useful when you suspect balanced rearrangements or triploidy.
- Alpha-fetoprotein and acetylcholinesterase in amniotic fluid diagnose open NTDs; CVS cannot.