What are the pros and cons of pre-implantation genetic testing for aneuploidy (PGT-A) in a 45-year-old woman considering in vitro fertilization (IVF)?

Pre-implantation Genetic Testing for Aneuploidy in a 45-Year-Old Woman

For a 45-year-old woman considering IVF, PGT-A should be approached with significant caution and realistic expectations, as the routine use is not proven to improve live birth rates per cycle, and at this advanced maternal age, the likelihood of having no euploid embryos available for transfer is substantial.

Critical Age-Related Considerations

At 45 years of age, the fundamental challenge is that aneuploidy rates in embryos are extremely high, and the probability of obtaining any euploid embryos after testing may be very low or zero 1. Studies report that up to 32% of patients undergoing PGT-A have no viable embryos available for transfer, and this percentage is significantly higher in women of advanced maternal age 1.

Pros of PGT-A at Age 45

Potential Benefits (Limited Evidence)

• Reduced miscarriage risk: PGT-A significantly reduces miscarriage rates by avoiding transfer of aneuploid embryos (RR = 0.48; 95% CI: 0.26-0.90) 2

• Fewer embryo transfers needed: When euploid embryos are available, PGT-A reduces the number of transfers required to achieve pregnancy, minimizing physical and emotional burden 3, 2

• Higher implantation rates per transfer: When analyzed on a per-embryo transfer basis (not per cycle), euploid embryos show improved pregnancy rates 4, 3

• Improved embryo selection with modern technology: Comprehensive chromosome screening (CCS) with blastocyst biopsy shows better outcomes than older FISH technology, with live birth rates significantly higher (RR = 1.30,95% CI 1.03-1.65) when CCS is used 5

Cons of PGT-A at Age 45

Major Limitations and Risks

• No improvement in live birth rates per cycle started: The most critical finding is that PGT-A does not improve ongoing pregnancy rates per cycle when routinely applied to the general IVF population 3. The cumulative live birth rate over 1 year shows no significant difference (24% with PGT-A vs 24% without, difference 0.83%, 95% CI: -7.60 to 9.18%) 2

• High likelihood of no transferable embryos: At age 45, the probability that all embryos will be aneuploid is substantial, potentially leaving no embryos for transfer after testing 1, 2

• Technical limitations and false results: Multiple factors cause sequencing errors including embryologist technique, limited DNA from biopsy, mitotic mosaicism, and sampling errors 1. High false-positive rates may actually reduce live birth chances 1

Physical and Procedural Burdens

• Substantial physical burden: The IVF process required for PGT-A carries inherent risks including preeclampsia, abnormal placentation, cesarean section, prematurity, low birth weight, and miscarriage 1

• Embryo biopsy risks: Potential trauma from biopsy and unknown long-term effects on the fetus 6

• Extended culture requirements: Embryos must be cultured to blastocyst stage (day 5-6), with associated embryo loss during prolonged in vitro culture 4

Financial and Psychological Considerations

• Significant cost: PGT-A is an expensive IVF add-on with costs that should be explicitly discussed, and its liberal use for advanced maternal age patients has not been shown to be effective 1, 4

• Psychological impact: Substantial psychological burden for couples, particularly if all embryos are found to be aneuploid 1

• Prolonged treatment timeline: The procedure extends the IVF timeline and requires embryo cryopreservation 4

Scope Limitations

• Cannot guarantee healthy child: PGT-A only screens for chromosomal abnormalities and cannot detect monogenic disorders, de novo mutations, or complex polygenic conditions 1, 7

• Environmental factors not addressed: Many conditions and traits are influenced significantly by environmental factors that PGT-A cannot predict 1

Evidence Quality and Applicability

The existing randomized controlled trials have significant limitations for a 45-year-old patient 4, 3:

• Most RCTs only included good prognosis patients with normal ovarian reserve producing high numbers of embryos 3
• Studies typically included women aged 36-40 years, not 45 years 2
• No appropriately designed RCT has been conducted using intention-to-treat analysis accounting for all parameters on a per-cycle basis 4

Clinical Recommendation Framework

PGT-A should only be considered for this 45-year-old patient if:

1. She has demonstrated good ovarian reserve and is expected to produce multiple embryos 3
2. She receives comprehensive counseling about realistic success rates (approximately 50-60% pregnancy rate overall, likely lower at age 45) 1
3. She understands the substantial possibility (potentially >50% at her age) of having no euploid embryos for transfer 1
4. She is counseled about all technical limitations including false-positive results, mosaicism, and the inability to detect all genetic conditions 6, 1
5. The procedure is performed at an experienced IVF clinic with expertise in blastocyst biopsy and comprehensive chromosome screening 3

The decision should prioritize the patient's values regarding: minimizing miscarriage risk versus maximizing the chance of having any embryo to transfer, as PGT-A may eliminate all available embryos in this age group 1, 2.