Is Preimplantation Genetic Testing for Aneuploidy (PGT-A) a guarantee of a successful pregnancy and a completely healthy child?

Preimplantation Genetic Testing for Aneuploidy (PGT-A) Is Not a Guarantee of a Successful Pregnancy or Healthy Child

PGT-A does not guarantee a successful pregnancy or a completely healthy child, with success rates of only approximately 50-60% of women achieving pregnancy after the procedure. 1

Understanding PGT-A and Its Limitations

PGT-A is an assisted reproductive technology that tests embryos created through in vitro fertilization (IVF) for chromosomal abnormalities before implantation. While it can help select embryos without certain genetic variants, it comes with significant limitations:

• The procedure involves a substantial physical burden for women and psychological impact for couples, with significant associated costs 1
• The process may take many months and is not always successful in leading to pregnancy and the birth of a healthy baby 1
• Success rates are limited, with only about 50-60% of women achieving successful pregnancies after PGT-A 1
• The IVF process required for PGT-A carries inherent risks including preeclampsia, abnormal placentation, cesarean section, prematurity, low birth weight, and miscarriage 1

Technical Limitations of PGT-A

Several technical factors limit the reliability of PGT-A:

• Multiple factors can result in sequencing errors, including:

  • Embryologist techniques and experience in embryo biopsy 1
  • Limited DNA obtained from a single biopsy (typically 5-8 cells) 1
  • Mitotic mosaicism (different cells having different chromosomal compositions) 1
  • Cell cycle phase variations 1
  • Sampling errors and limited collection of cells in the trophectoderm biopsy 1

• These limitations mean abnormal cells may be collected in an otherwise normal embryo or vice versa, raising concerns about the accuracy of genetic testing based on embryo biopsy 1

Clinical Validity and Utility Concerns

The clinical utility of PGT-A remains controversial:

• The American College of Obstetricians and Gynecologists (ACOG) states that routine use of PGT-A for IVF in infertile women is not proven 1
• Recent studies have highlighted potential decreases in cumulative live birth rates for younger patients undergoing embryo transfer with PGT-A 2
• There has not yet been an appropriately designed randomized controlled trial of blastocyst biopsy PGT-A analyzed by intention-to-treat that accounts for all relevant parameters on a per-cycle basis 3
• High false-positive rates have been reported, which may actually reduce live IVF birth chances for many patients 4

Beyond Chromosomal Abnormalities

PGT-A only screens for chromosomal abnormalities and cannot guarantee a completely healthy child for several reasons:

• Environmental factors play a significant role in the development of many conditions and traits 1
• PGT-A cannot detect all possible genetic disorders, particularly those caused by de novo mutations or complex polygenic conditions 1
• The test cannot predict or prevent conditions that develop after birth due to environmental exposures, infections, or injuries 1

Ethical Considerations

Several ethical concerns surround PGT-A:

• Questions about the clinical utility of PGT-A with potential gains characterized as uncertain and relatively limited 1
• Concerns about eugenics and "designer babies" as technology evolves 1
• Lack of inclusivity since genome-wide association studies that PGT-A is based on mainly use data from people of European ancestry, making it less effective for those with non-European ancestries 1

Practical Considerations for Patients

When considering PGT-A, patients should be counseled about:

• The expected costs of the procedure 1
• Realistic success rates (approximately 50-60%) 1
• The duration of the trajectory 1
• The procedure of in vitro fertilization and its inherent risks 1
• The possibility that no viable embryos may be available for transfer (reported in up to 32% of cases in some studies) 1

Current Recommendations

Current guidelines suggest:

• Only PGT for monogenic disorders (PGT-M) and pre-implantation testing for structural chromosome rearrangements are broadly recommended 1
• PGT-A should be considered on a case-by-case basis with appropriate counseling about its limitations 1
• Each clinic should evaluate the efficacy of PGT-A in their IVF program based on their specific population, skills, and limitations 5