Preimplantation Genetic Testing for Aneuploidy

Introduction to PGT-A

• The American College of Obstetricians and Gynecologists (ACOG) states that routine use of PGT-A for IVF in infertile women is not proven, with success rates of only approximately 50-60% of women achieving pregnancy after the procedure 1, 2
• PGT-A involves a substantial physical burden for women and psychological impact for couples, with significant associated costs 1, 2

Technical Limitations of PGT-A

• Multiple factors can result in sequencing errors, including embryologist techniques and experience in embryo biopsy, limited DNA obtained from a single biopsy, mitotic mosaicism, cell cycle phase variations, and sampling errors 3, 4
• The IVF process required for PGT-A carries inherent risks including preeclampsia, abnormal placentation, cesarean section, prematurity, low birth weight, and miscarriage 3, 4

Clinical Validity and Utility Concerns

• The clinical utility of PGT-A remains controversial, with high false-positive rates reported, which may actually reduce live IVF birth chances for many patients 3, 4

Beyond Chromosomal Abnormalities

• PGT-A only screens for chromosomal abnormalities and cannot guarantee a completely healthy child, as environmental factors play a significant role in the development of many conditions and traits 5
• PGT-A cannot detect all possible genetic disorders, particularly those caused by de novo mutations or complex polygenic conditions 4, 5

Ethical Considerations

• Questions about the clinical utility of PGT-A with potential gains characterized as uncertain and relatively limited, and concerns about eugenics and "designer babies" as technology evolves 5
• 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 5

Practical Considerations for Patients

• Patients should be counseled about the expected costs of the procedure, realistic success rates (approximately 50-60%), the duration of the trajectory, and the procedure of in vitro fertilization and its inherent risks 1, 2, 3, 4
• The possibility that no viable embryos may be available for transfer (reported in up to 32% of cases in some studies) should also be discussed with patients 3, 4

Current Recommendations

• Only PGT for monogenic disorders (PGT-M) and pre-implantation testing for structural chromosome rearrangements are broadly recommended, while PGT-A should be considered on a case-by-case basis with appropriate counseling about its limitations 3, 4

Pre-implantation Genetic Testing for Aneuploidy in Advanced Maternal Age

Embryo Biopsy Risks and Limitations

• The American Society for Reproductive Medicine acknowledges that embryo biopsy risks include potential trauma from biopsy and unknown long-term effects on the fetus 6, 7

Clinical Considerations

• The American College of Medical Genetics and Genomics recommends that PGT-A should only be considered for patients who have demonstrated good ovarian reserve and are expected to produce multiple embryos, and who receive comprehensive counseling about realistic success rates and technical limitations 6, 7