The pros and cons of preimplantation genetic testing for aneuploidy (PGT-A)

Key Takeaways

• PGT-A helps by screening embryos for chromosomal abnormalities, so doctors can select embryos most likely to implant and result in a healthy birth. It is not a guarantee or a substitute for comprehensive prenatal testing.
• The test can lower miscarriage risk and boost implantation for certain patients, such as those who experience recurrent pregnancy loss or are of older maternal age. However, advantages differ by patient.
• Embryo biopsy has a minor risk of damage and some embryos do not survive biopsy, freezing, or thawing. It is important to balance clinical benefits with possible loss of potential embryos.
• Mosaicism and technical limitations can confound the interpretation of results. Talk about potential false positives or negatives and what follow-up might be possible with a genetics team.
• PGT-A adds significant cost to IVF and may not be covered by insurance. Weigh projected costs against the potential long-term savings of fewer failed cycles before committing.
• Take into consideration your medical history, age, number and quality of embryos, emotional values, and ethical considerations. Discuss with your fertility clinic in order to have a transparent, personalized plan.

PGT-A testing pros and cons are the advantages and disadvantages of preimplantation genetic testing for aneuploidy. It can increase implantation rates and reduce miscarriage risk by testing embryos for chromosome anomalies.

However, it adds cost, adds embryo biopsy, and can miss mosaicism. Couples balance enhanced chances of success with cost, delay, and ethical concerns.

The following sections parse clinical data, price considerations, and decision-making.

Understanding PGT-A

PGT-A is a preimplantation genetic test used during in vitro fertilization (IVF) to screen embryos for whole-chromosome abnormalities before transfer. It’s among a handful of genetic tools fertility clinics deploy to take the guesswork out of embryo selection and patient decision-making.

What is PGT-A and when is it performed? PGT-A is a genetic test that can be done on embryos during IVF to screen for chromosomal abnormalities prior to transfer. The biopsy generally takes place at the blastocyst stage, approximately 5 to 6 days post-fertilization, when the embryo has developed an inner cell mass and trophectoderm that can be sampled with minimal risk to the embryo.

A few cells are extracted from the trophectoderm and sent to a genetics lab for chromosomal scrutiny.

Main function and anticipated advantages. The primary goal of PGT-A is to identify euploid embryos — embryos with the normal chromosome complement — so the likelihood of implantation and live birth is increased and miscarriage risk is decreased. PGT-A can improve IVF success rates by up to 50%, studies report, and in some series the proportion of screened embryos that progressed to delivery was much greater than control embryos, 66.4% compared to 47.9%.

For women over 37, there is some evidence that it improves live birth chance, with one study estimating that 21 cycles or 35 transfers would need to be treated to increase live birth by one baby.

The test and lab process. After biopsy at day 5 to 6, the cells are subject to DNA amplification and chromosome analysis by next generation sequencing or similar methods. The lab returns results indicating if embryos are euploid, aneuploid, or mosaic. Results direct which embryo to transfer or if freezing embryos for future transfer.

Day 7 blastocysts have lower euploidy rates but similar sustained implantation rates compared to day 5 and day 6 blastocysts, so clinics occasionally factor day 7 embryos into selection choices.

Background on prevalence and age impact. Aneuploidy rates rise with maternal age. One dataset shows that 52.0% of embryos were aneuploid in women younger than 35, versus 64.5% in women aged 35 to 40. Another overall aneuploidy rate in a different study was 31% with a mean maternal age of 35.1 years.

These numbers provide a sense of how many embryos might be viable for transfer post-screening.

Limitations and cost issues. PGT-A is not cost-effective for all patients. A modeled study found PGT-A for unexplained recurrent pregnancy loss reduced miscarriages but was not cost-effective compared with expectant management. Tests can’t pick up every genetic condition and can provide ambiguous mosaic results that make decision making harder.

The PGT-A Debate

Since that time, PGT-A has been a hot-button topic among fertility experts, with debate around its actual clinical value and its limitations. The test is designed to choose chromosomally normal embryos to transfer. Research is mixed on whether that selection consistently increases live birth rates among any patient population. Data does indicate an advantage in some populations, but concerns persist around expense, accuracy and unforeseen damage.

1. Increased Success?

PGT-A is meant to enhance IVF success by transferring only chromosomally normal embryos. PGT-A proponents cite studies showing higher implantation and pregnancy rates after PGT-A, especially in older women and clinics using day-5 biopsies and excellent lab protocols.

For women over 37, pooled data indicate an enhanced chance of live birth. One research calculated a number needed to treat of 21 cycles, or 35 embryo transfers, to result in 1 extra live birth. The data is most compelling where embryo aneuploidy is prevalent.

For instance, aneuploidy rates increase from approximately 52.0% in women under 35 to around 64.5% in those 35 to 40, meaning selection may be more beneficial in older groups. More success is not assured for patients with just a handful of embryos. In low-yield cycles, testing may simply discard rare embryos with marginal probability, reducing options overall and resulting in no net improvement.

2. Reduced Miscarriage?

PGT-A can decrease miscarriages through weeding out embryos with chromosomal abnormalities associated with early loss. Multiple studies demonstrate decreased clinical pregnancy loss following euploid embryo transfer, and some clinics experience increased term pregnancies.

Patients with recurrent pregnancy loss due to embryonic aneuploidy, for example, would be the ones most likely to benefit from such targeted testing. Miscarriage risk isn’t removed, since uterine, immunologic and maternal health causes lead to losses.

While some studies observe lower miscarriage rates, there is no obvious enhancement of the live-birth rate. Fewer miscarriages don’t necessarily translate into more babies born.

3. Emotional Relief?

PGT-A offers emotional relief by removing some of the unknown. It reduces anxiety for many patients. Just knowing a transferred embryo was screened can increase confidence and reduce stress around transfer and early pregnancy monitoring.

Waiting for results and the additional choices around mosaic or surplus embryos can bring new stress. Fewer broken cycles might reduce trauma, but the procedure and possibility of complicated outcomes can instead inflict new wounds.

4. Embryo Risk?

Biopsy poses a slight danger of harming embryos and influencing development. Moving biopsy from day 3 to day 5 has greatly diminished that risk, but there are still embryos that do not survive biopsy and vitrification.

Not every embryo tolerates double biopsy or double vitrification. In one study, the clinical pregnancy rates were 31% compared to 54.3% with single procedures, suggesting potential procedural harm.

5. Mosaicism Puzzle?

Mosaic embryos have both normal and abnormal cells, making them difficult to interpret. Transfers can yield healthy babies, but the outcomes are less predictable. A few clinics will allow mosaic transfer with careful counseling.

Decision-making is often nuanced and in some cases can be very case-specific.

6. Accuracy Limits?

PGT-A is cutting edge but not perfect. False positives and negatives happen. Technical factors and lab protocols are important. One study found a positive predictive value of 96% for SNP microarray.

However, sampling error and selection bias (day-3 vs. Day-5 practices) can skew results.

7. Financial Burden?

PGT-A introduces considerable upfront expense, typically not covered by insurance. Patients need to balance risk and reward. Theoretical models suggest it wasn’t cost-effective for unexplained recurrent loss versus expectant management.

Make a price comparison to direct planning.

Beyond The Numbers

PGT-A is about more than just a lab report. It finds itself at the crossroads of clinical data, individual aspirations, and moral decisions. Basic facts matter: some studies show PGT-A may raise pregnancy chances and cut miscarriage risk in older women, and it lowers the number of embryos transferred and the risk of multiples. Live birth advantages are still controversial, mosaic embryos muddy the waters, and tests can yield both false-positive and false-negative results.

These constraints inform how one ought to consider PGT-A beyond the cold numbers. Personal values about disability, parenthood, and genetic risk play a significant role in decision-making. The emotional cost of repeated cycles, waiting, and uncertainty can weigh heavily on individuals. Additionally, tolerance for ambiguous results such as mosaic findings can vary among patients.

Financial capacity and willingness to pay for extra testing also influence choices. Access to specialized labs and experienced embryologists is crucial for many couples. Timing pressures, such as age-related fertility decline, further complicate the landscape. The wish for family balancing or escape from known family disorders adds another layer of complexity. Cultural or religious views on embryo selection or disposal can also shape decisions.

Emotional and ethical considerations count. A lot of patients that we see experience grief after a failed cycle and they feel pressure that they need to check every test. Some will pay additional costs and time in order to minimize miscarriage risk. Others will steer clear of PGT-A because they like to transfer without selection, either for moral or cultural reasons.

Clinicians should have the conversation about whether results would alter plans and how families would respond to ambiguous results such as mosaicism. Unique scenarios change the risk-benefit picture. For couples with a known single-gene disorder, PGT for monogenic disease often offers clear value. In contrast, PGT-A for unexplained recurrent loss has limited evidence of cost-effectiveness.

Women over 40 may benefit more from PGT-A because aneuploidy risk rises with age. Yet some still produce euploid embryos and achieve pregnancy without testing. For those wanting family balancing, PGT-A can be used alongside sex selection methods, but this raises ethical and policy considerations that vary by country.

Technical and pragmatic considerations inform actual consumption. Biopsy timing matters. Day 5 to 6 trophectoderm biopsy may give more accurate results than day 3 blastomere biopsy. Concordance between PGT-A and the embryo’s actual chromosomal composition is not perfect. Even so-called mosaic embryos occasionally implant and result in healthy babies.

Emerging minimally invasive options such as cell-free DNA extracted from spent culture medium are promising but remain reliant on sampling timing and technique and require additional investigation. PGT-A decisions need to combine clinical information with individual values, straightforward guidance on restrictions, and pragmatic expectations regarding success and expenses.

Is PGT-A For You?

PGT-A is a tool, not a promise. It screens embryos for whole-chromosome abnormalities to aid in embryo selection for transfer. Use the points below to decide if the test matches your fertility plan and to direct a targeted conversation with your clinic and genetic counselor.

Your Age

Maternal age is a significant predictor of embryo aneuploidy. Chromosomal abnormalities are present in approximately 50% of embryos formed through IVF, and risk increases with age. For patients over 37, PGT-A significantly increases pregnancy rates and can boost IVF success by as much as around 50% in some studies.

It can reduce the risk of pregnancy loss from approximately 32% to approximately 15%. Younger patients under 37 typically have less obvious benefit. If embryo quality and quantity are good, PGT-A might not boost your odds of conception significantly.

PGT-A guided single embryo transfer can reduce the risk of twins, thereby reducing pregnancy complications.

Your History

Because medical, reproductive and family history counts. Recurrent pregnancy loss, prior failed IVF cycles or known familial genetic conditions can shift the balance toward PGT-A. If you are a couple who has had numerous failed transfers, PGT-A allows you to concentrate transfers on euploid embryos and possibly decrease your time to pregnancy.

Single gene disorder carriers or families with chromosomal rearrangements can opt for targeted testing in addition to or instead of standard PGT-A. This includes cystic fibrosis carrier couples or those with a known balanced translocation. Documenting miscarriages, prior genetic testing and family history provides the clinic context to select appropriate tests and interpret results.

Your Embryos

Your number and quality of embryos will impact how useful PGT-A is. If you generate a lot of good-quality blastocysts, PGT-A ranks them and facilitates single embryo transfer. With multiple embryos, you can screen and bank euploid embryos for future cycles as well, which boosts cumulative live birth potential.

If only one or two embryos are available, PGT-A introduces risk. An embryo labeled aneuploid might actually be mosaic or false-positive, and you could lose the chance to transfer. Monitor embryo development (day 5 – 6 blastulation, grading) and review biopsy timing and lab expertise.

Consider cost: PGT-A can run roughly $4,000 to $10,000 for screening about eight embryos, so weigh financial limits alongside clinical factors.

The Cost Equation

PGT-A introduces a separate cost element to IVF treatment. The sticker price for an IVF cycle is usually around 4,500, but most clinics charge more when you add in monitoring, meds, lab work and embryo storage. PGT-A is typically performed in conjunction with IVF and has separate charges for biopsy, genetic testing, and sometimes expedited lab services. Those fees differ by lab and location and can tip the scale around the economics of a single IVF try versus a multi-cycle strategy.

• Pros (dollars).
  • May cut total cycles: Studies report higher success per transfer in some groups, meaning fewer full IVF cycles may be needed, saving on cycle costs, medications, and time off work.
  • Lower miscarriage costs: Reduced miscarriage rates for some patients can lower emotional, medical, and follow-up costs tied to pregnancy loss.
  • Better embryo selection: Fewer transfers of nonviable embryos can reduce waste of resources and clinic fees and can speed time to pregnancy.
  • Targeted use benefits older patients: For women over 35, the higher risk of chromosomal issues can make PGT-A more cost-effective by improving selection and reducing repeated cycles.
• Cons (dollars).
  • Upfront expense: PGT-A adds significant immediate cost to an already costly IVF episode. This may be prohibitive for many.
  • Mixed evidence: Some studies show no clear outcome improvement, making the extra spending less justifiable for some patients.
  • Multiple rounds raise costs: If multiple IVF rounds are necessary to obtain euploid embryos, PGT-A costs can accumulate and surpass savings.
  • Insurance limits: Many insurers do not cover PGT-A, placing full cost on patients.

Compare short-term outlay and long-term savings by modeling scenarios. Example A: one IVF cycle at 4,500 plus PGT-A for 2,000 yields a higher first-cycle cost but may avoid a second 4,500 cycle if PGT-A improves selection, netting a potential net saving.

Example B: if PGT-A does not improve outcome, the patient pays extra with no reduction in future cycles. Calculate probable outcomes with clinic success rates and miscarriage information to estimate expected cycles with and without PGT-A.

Practical advice: Check insurance policy language for genetic testing and IVF coverage. Request clinics for detailed pricing — storage, biopsy, lab, etc. Ask about in-house versus external lab costs and whether they have payment plans or cycle bundles.

Make a quick pro/con list that plots probable clinical benefit against anticipated cost given personal age, ovarian reserve, and previous IVF history for a cost-conscious decision.

Future Perspectives

PGT-A occupies the intersection of incremental lab advances, fluctuating economics, and changing ethics. Some of the more near-term advances in genetic screening and IVF practice ought to increase accuracy and provide clinicians with crisper signals when selecting embryos. Enhancements in biopsy technology, lab culture conditions, and sequencing depth will reduce noise from mosaicism and sampling error.

Non-invasive PGT (niPGT) testing either spent embryo culture media or cell-free DNA provides a path to minimize embryo damage while providing more uniform samples, although technique standardization and validation are still works in progress.

Polygenic risk scoring is fast advancing. They are developing better algorithms that incorporate thousands of these common variants to predict lifetime risk of complex diseases. In embryo work, those points now contribute marginal, probabilistic indications instead of determinisms.

Future tests could mix polygenic scores with single-gene discoveries, chromosomal information, and established environmental risk factors to provide a more comprehensive risk profile for traits or conditions. That holistic perspective might aid couples in making trade-offs when multiple embryos are implanted, for instance, preferring an embryo with a reduced predicted risk for early-life heart disease in addition to normal chromosomes.

Cost and access will probably alter practice. As sequencing prices decrease and lab workflows scale, PGT-A and polygenic options may transition from boutique to more standard care in many settings. More broadly, greater availability could help more patients sidestep the exhausting grind of multiple IVF cycles and bring down miscarriages associated with aneuploid embryos.

Wider uptake raises equity questions: who pays, which clinics offer full counseling, and how do poorer regions adopt safe standards? Public and private payers, along with global guideline organizations, will impact adoption by determining coverage and quality standards.

Regulation and ethics will drive what is allowed. Policy makers need to balance reproductive autonomy against worries about eugenics, discrimination, and unbalanced social outcomes. Other experts anticipate stricter regulations on non-medical selection while allowing medically necessary usage.

Others caution that lax oversight may result in abuse or overpromising regarding what polygenic screening can provide. Well-defined lab standards and requirements for counseling and reporting test limitations will help to keep patients’ expectations in check.

Being in the know counts. Patients and clinicians must monitor validation studies, consensus guidelines, and outcome data over time. These new approaches could shift which embryos are prioritized, what prices are paid, and how outcomes are advised.

Conclusion

PGT-A can eliminate the risk of implanting an embryo with an abnormal number of chromosomes. For certain individuals, it may accelerate the route to one healthy pregnancy. The test adds cost and does not fit every case. Lab skill, embryo quality, and clinic track record shape results. A few ‘abnormal’ embryos still result in healthy babies. Some of the normal embryos do not implant.

Consider age, fertility history, budget, and embryo count. Discuss success rates and lab techniques with your clinic. Demand data, not promises. Select the road that offers you a combination of hope, expense, and reasonable chances.

If you want a more in-depth look at your options or some sample questions to bring to your doctor, I’ve got you covered.

Frequently Asked Questions

What is PGT-A and how does it work?

PGT-A tests embryos for aneuploidy. Labs sample a handful of cells from embryos and assay them. Results are intended to select embryos with a normal chromosome count for transfer.

What are the main benefits of PGT-A?

PGT-A can minimize failed transfers and miscarriages associated with chromosomal abnormalities. It might assist in selecting embryos with higher implantation potential, particularly in older patients or those with recurrent pregnancy loss.

What are the main limitations or risks of PGT-A?

PGT-A can misclassify embryos because of mosaicism or sampling error. It doesn’t guarantee pregnancy and adds lab manipulation risks. Some healthy embryos may be discarded based on results.

Who might benefit most from PGT-A?

Individuals over 35, multiple IVF failures, recurrent miscarriage, or a lot of embryo selection to do often receive the most actionable information from PGT-A.

How much does PGT-A typically add to IVF costs?

It ranges in price depending on the country and clinic. Anticipate a hefty surcharge on top of IVF, typically a few hundred to a few thousand local currency. Request a transparent price estimate from your clinic.

Can PGT-A improve live birth rates for younger patients?

The data is contradictory. For young patients with excellent embryo quality, PGT-A is unlikely to improve live birth rates and it may do harm by inadvertently discarding embryos that are viable but mosaic.

Are there ethical concerns with PGT-A?

Yes. Worries around embryo choice, biased culling, and lack of equal accessibility due to expense exist. Talk through your ethics and personal values with your clinic and support people.