What are the considerations for pre-implantation genetic testing for aneuploidy (PGT-A) in a 45-year-old woman undergoing in vitro fertilization (IVF) with advanced maternal age?

PGT-A in a 45-Year-Old Woman: Key Considerations

PGT-A is not routinely recommended for a 45-year-old woman undergoing IVF, as the clinical utility remains unproven and the likelihood of obtaining euploid embryos is extremely low at this age, with success rates dropping to near zero after age 45. 1, 2, 3

Age-Specific Success Rates and Biological Reality

• Women aged 45 and older have exceptionally poor outcomes with PGT-A, with only 2.6% delivery rate per cycle in women aged 45.0-45.9 years, and no euploid blastocysts found in patients older than 45.9 years 3
• The overall euploidy rate in women aged 44-47 is only 11.8%, meaning approximately 9 out of 10 embryos will be aneuploid 3
• In 32% of advanced maternal age cases, no viable embryos are available for transfer after PGT-A screening, which represents a critical counseling point 1, 2
• A recent study showed ongoing pregnancy rates improved in women ≥38 years with PGT-A implementation, but the high rate of no transferable embryos complicates this conclusion 1

Current Guideline Recommendations

• The American College of Obstetricians and Gynecologists (ACOG) explicitly states that routine use of PGT-A for IVF in infertile women is not proven and therefore not currently recommended 1, 2
• Only PGT for monogenic disorders (PGT-M) and preimplantation testing for structural chromosome rearrangements (PGT-SR) are broadly recommended by professional societies 1, 2, 4
• The American College of Medical Genetics and Genomics (ACMG) recommends PGT-A should only be considered for patients with demonstrated good ovarian reserve who are expected to produce multiple embryos 2

Technical and Clinical Limitations

Accuracy Concerns

• PGT-A has high false-positive rates that may actually reduce live IVF birth chances for many patients 2, 5
• Multiple factors result in sequencing errors including embryologist technique, limited DNA from single biopsy, mitotic mosaicism, cell cycle variations, and sampling errors 2
• A single trophectoderm biopsy may not accurately represent the genetic makeup of the inner cell mass 1
• PGT-A was never clinically validated in its ability to define embryos as chromosomally normal, mosaic, or aneuploid, nor certified by regulatory bodies 5

Inherent IVF Risks

• The IVF process required for PGT-A carries substantial risks including preeclampsia, abnormal placentation, cesarean section, prematurity, low birth weight, and miscarriage 1, 2
• Embryo biopsy itself poses potential trauma risks with unknown long-term effects on the fetus 2
• Studies have identified increased risks of birth defects and imprinting disorders with IVF 1

What PGT-A Cannot Detect

• PGT-A only screens for chromosomal abnormalities and cannot guarantee a healthy child, as it does not detect monogenic disorders, de novo mutations, or complex polygenic conditions 2, 4
• Environmental factors play significant roles in development of many conditions and traits that PGT-A cannot account for 2

Practical Counseling Points for This Patient

Realistic Expectations

• Overall success rates with PGT-A are only approximately 50-60% for achieving pregnancy, but this drops dramatically at age 45 2
• At age 44.0-44.9 years, delivery rate per cycle is 10.6%; at 45.0-45.9 years it drops to 2.6% 3
• The procedure involves substantial physical burden and psychological impact with significant associated costs 2

Decision-Making Algorithm

1. Assess ovarian reserve first - PGT-A should only be considered if good ovarian reserve is demonstrated and multiple embryos are expected 2
2. If age ≥45 years: Extensive counseling about very low odds of success (near zero for euploid embryos) and high risk for embryonic aneuploidies is mandatory 3
3. If age 44-44.9 years with good ovarian reserve: PGT-A may be considered on a case-by-case basis with comprehensive counseling about the 10.6% delivery rate per cycle and 68% chance of cycle cancellation 3
4. Discuss the 32% probability of having no transferable embryos after completing the entire PGT-A process 1, 2

Alternative Approach

• Morphology-based embryo selection with fresh transfer remains a valid alternative, particularly given the lack of proven clinical utility for routine PGT-A 1, 2, 6
• Recent pilot RCT data in women aged 35-42 showed no significant differences between PGT-A and morphology-based selection in clinical pregnancy rates (50% vs 40%), live birth rates (50% vs 38%), or miscarriage rates (12% vs 8%) 6

Critical Pitfalls to Avoid

• Do not present PGT-A as a standard or recommended procedure - it remains investigational and unproven for routine use 1, 2
• Avoid giving false hope - at age 45, the biological reality is that very few if any euploid embryos will be obtained 3
• Do not proceed without discussing the high likelihood of cycle cancellation due to no euploid embryos being available 1, 2, 3