What is the recommended approach for taking a sample for chromosomal analysis in cases of fetal demise (intrauterine fetal death)?

Chromosomal Analysis Sampling in Fetal Demise

For fetal demise, amniocentesis performed prior to uterine evacuation is the most reliable method for obtaining chromosomal analysis, with a 100% success rate compared to only 28-78% success with fetal tissue sampling. 1, 2

Recommended Sampling Approach

First-Line: Amniocentesis Before Delivery/Evacuation

Perform transabdominal amniocentesis immediately upon diagnosis of fetal demise and before labor induction or uterine evacuation. 1, 2

• Amniocentesis achieves successful cytogenetic results in 85-100% of cases, significantly superior to postpartum tissue analysis 1, 2
• This approach should be performed nonselectively for all fetal deaths regardless of gestational age, maternal age, presence of morphologic abnormalities, or degree of maceration 2
• Amniotic fluid cells remain viable for culture even when fetal tissues are severely macerated 1, 2

Alternative: Placental Tissue (If Amniocentesis Not Performed)

If amniocentesis was not performed before delivery, placental tissue is the preferred alternative specimen 3

• Fresh placental tissue should be collected immediately after delivery and transported appropriately 4
• Avoid prolonged formalin fixation, as formalin-fixed paraffin-embedded tissue has low success rates in many laboratories 4

Backup: Fetal Tissue with Chromosomal Microarray Analysis (CMA)

When traditional karyotyping fails due to culture failure, chromosomal microarray analysis provides superior diagnostic yield 3, 5

• CMA does not require viable dividing cells, making it ideal for macerated or nonviable tissue 3, 5
• CMA increases diagnostic yield from 73% to 94% compared to karyotype alone 5
• Fetal skin is the preferred tissue source for CMA when amniocentesis was not performed 3
• CMA detects an additional 5.6% of abnormalities beyond what karyotype identifies 3

Specific Tissue Collection Guidelines

Optimal Specimens (in order of preference):

1. Amniotic fluid (collected before delivery) - 100% success rate 1
2. Fresh placental tissue - reasonable alternative 3
3. Fetal skin tissue - best fetal tissue for CMA 3
4. Cultured fibroblasts from skin - if fresh tissue transport available 4

Unacceptable Specimens:

• Hair, vitreous fluid, synovial fluid, and urine are not suitable due to low DNA yield and contamination risk 4
• Severely macerated fetal tissue has only 35% success rate with traditional karyotyping 2

Critical Technical Considerations

Clean skin with alcohol only, never iodine-containing compounds, as iodine inhibits cell culture growth 4

• Collect specimens as soon as possible after diagnosis of demise 4
• Document time of collection after death and storage conditions for laboratory acceptance 4
• Transport fresh tissue on ice or with dry ice if previously frozen; formalin-fixed tissue can be transported at room temperature 4

Clinical Algorithm for Fetal Demise

1. Upon diagnosis of intrauterine fetal demise: Perform transabdominal amniocentesis immediately before proceeding with delivery or evacuation 1, 2

2. If amniocentesis not performed: Collect fresh placental tissue immediately after delivery, clean with alcohol (not iodine), and transport appropriately 4, 3

3. Order both karyotype AND chromosomal microarray analysis to maximize diagnostic yield, as CMA provides an incremental 5.6% detection rate and does not require viable cells 3, 5

4. If initial karyotype fails due to culture failure: Reflex automatically to CMA on stored tissue 5

Diagnostic Yield and Clinical Value

• Chromosomal abnormalities are found in 13% of all fetal deaths and 38% of those with morphologic abnormalities 2
• Even without morphologic abnormalities, the probability of chromosomal abnormality remains 4.6% 2
• Cytogenetic analysis determines the cause of death in 19% of cases and is essential for counseling regarding recurrence risk 2, 3

Common Pitfalls to Avoid

Do not use selective criteria (such as maternal age >35, small for gestational age, or presence of anomalies) to decide whether to perform chromosomal analysis, as this approach misses significant abnormalities 2

• Do not rely solely on postpartum fetal tissue sampling, which has unacceptably high failure rates of 22-72% 1, 2
• Do not delay specimen collection, as tissue viability decreases with time after demise 4
• Do not order karyotype alone without CMA backup, as this misses copy number variants detectable only by microarray 3, 5