Is it medically accepted to act on a Fluorescence In Situ Hybridization (FISH) result from amniocentesis before receiving confirmation of the diagnosis with karyotype or chromosomal microarray?

Acting on FISH Results from Amniocentesis Before Karyotype or Microarray Confirmation

It is medically acceptable to act on FISH results from amniocentesis before receiving confirmation with karyotype or chromosomal microarray, but FISH should be considered a preliminary result and not a standalone diagnostic test. 1

Guidelines for Using FISH Results in Clinical Decision-Making

Role of FISH in Prenatal Diagnosis

• FISH provides rapid preliminary results (within 24-48 hours) compared to traditional karyotyping (10-14 days)
• Particularly valuable in time-sensitive clinical scenarios:
  • Advanced gestational age
  • Pregnancies complicated by fetal anomalies
  • Cases where management options would be limited by waiting for standard results 1

Limitations of FISH Testing

1. Detection capabilities: FISH primarily detects numerical abnormalities (aneuploidies) but cannot identify most structural rearrangements 1
2. Probe limitations: Only tests for specific chromosomes targeted by the probes used (typically chromosomes 13,18,21, X and Y) 2
3. Technical considerations: Signal interpretation challenges including cross-hybridization and mosaicism detection 1

Accuracy and Reliability

• FISH detects approximately 81% of chromosome aberrations identified by conventional analysis 2
• When FISH results are normal, there remains a residual risk of undetectable chromosome aberrations:
  • 1 in 177 for advanced maternal age
  • 1 in 60 for increased risk based on maternal serum screening
  • 1 in 43 when ultrasound reveals fetal anomalies 2

Clinical Algorithm for Acting on FISH Results

When FISH Results Are Positive

1. Numerical abnormalities (trisomies 13,18,21, sex chromosome aneuploidies):

   • May initiate clinical management discussions with patients
   • Chromosome analysis on either CVS or amniocentesis demonstrating nonmosaic trisomy consistent with the FISH result is considered confirmation 1
   • Final management decisions should await karyotype confirmation when possible

2. For mosaic results:

   • Do not consider as definitive confirmation
   • Particularly important with CVS results, which cannot distinguish between confined placental mosaicism and true fetal mosaicism 1
   • Follow-up amniocentesis is warranted in all cases of mosaicism observed on CVS 1

When FISH Results Are Normal

• Continue with standard karyotype analysis or chromosomal microarray
• Normal FISH results do not exclude:
  • Structural chromosomal abnormalities
  • Microdeletions/microduplications
  • Mosaicism below detection threshold
  • Abnormalities in chromosomes not targeted by the FISH probes 1, 2

Important Considerations for Clinical Practice

Documentation and Informed Consent

• The investigational nature of FISH testing should be described to patients 1
• Patients should understand that FISH is an adjunct test, with standard chromosomal analysis serving as the primary diagnostic and confirmatory evaluation 1
• Patient management decisions should ideally not be based on results obtained by FISH alone 1

Special Circumstances

• In time-sensitive situations (e.g., late gestational age with fetal anomalies), acting on FISH results may be necessary before karyotype confirmation 1
• When FISH is used prior to fetal reduction in multiple pregnancies, it has shown 90% sensitivity and 99.4% specificity for detecting abnormalities 3

Conclusion

While FISH provides valuable rapid preliminary results in prenatal diagnosis, it should be considered an adjunct to standard cytogenetic analysis rather than a replacement. Clinical decisions based solely on FISH should be made with caution and with full understanding of the test's limitations.