PGT-A: Does Preimplantation Genetic Testing for Aneuploidy Truly Improve IVF Success Rates? Evidence & Limitations

Q: Does an embryo diagnosed as "normal" by PGT-A guarantee pregnancy?

No. **In numbers: the positive predictive value of a euploid result is no higher than 50–60%** (PMID: 37192834). A "normal" result still fails to implant **four to five times out of ten. The field calls this unexplained gap "the black box of implantation." The same review lists factors associated with euploid blastocysts still failing: * Reduced inner cell mass quality (odds ratio 0.37) or trophectoderm quality (0.53) * Blastocyst quality below Gardner BB (0.40) * Developmental delay (0.56) * Age 38 or over (0.87), obesity (live birth 0.66 / miscarriage 1.8), previous repeated implantation failure (0.72) ★Most of the included studies were retrospective or small, and **the authors rate the certainty of evidence as low or very low.** ★It should also be noted that the authors include staff of a company providing PGT (Juno Genetics), and several are affiliated with the IVIRMA Global Research Alliance. This conflict of interest runs in PGT-A's favour and should be kept in mind.

The hope for a successful pregnancy during your In Vitro Fertilization (IVF) journey is immense. Amidst this, "PGT-A (Preimplantation Genetic Testing for Aneuploidy)," a technique to screen embryos for chromosomal abnormalities, has garnered significant attention. However, it's crucial to avoid the misconception that "PGT-A guarantees pregnancy." Let's take an objective look at whether this test truly improves IVF success rates, examining its scientific basis and the limitations we in the #TTCcommunity should be aware of.

Your fertility journey is uniquely yours, and the anxieties and questions you experience are valid and shared by many. We aim to provide accurate, evidence-based information to help you make informed decisions and navigate your path with clarity and peace of mind.

What is PGT-A?

PGT-A stands for Preimplantation Genetic Testing for Aneuploidy. It's a procedure performed during IVF where embryos are screened for an abnormal number of chromosomes (aneuploidy) before being transferred to the uterus. Chromosomal aneuploidies are a leading cause of implantation failure and miscarriage. This test primarily involves taking a small biopsy from the outer layer of the embryo (trophectoderm cells) and performing genetic analysis to identify embryos with a normal chromosome count (euploid embryos) for transfer.

Expected Benefits of PGT-A

The introduction of PGT-A has brought about several anticipated benefits:

Improved Implantation Rates and Reduced Miscarriage Rates: By transferring euploid embryos, PGT-A may reduce the risk of implantation failure and early miscarriage caused by aneuploid embryos. Note, however, that as set out below, a "normal" result still implants only 50–60% of the time.
Fewer Embryo Transfers and Potentially Shorter Time to Pregnancy: Selecting chromosomally normal embryos for transfer may reduce the number of unsuccessful transfer cycles, potentially shortening the overall time it takes to achieve pregnancy.
Reduced Risk of Multiple Pregnancies: By selecting a single, high-quality embryo for transfer, the risk of multiple gestations can be mitigated.

Scientific Evidence and Limitations of PGT-A

While PGT-A offers promising potential, especially for certain age groups, it's essential to understand its limitations. Research has highlighted the following points:

Varying Benefits by Age Group: For older women (e.g., late 30s to 40s and beyond), where the incidence of chromosomally abnormal embryos is higher, PGT-A may help improve implantation rates and reduce miscarriage rates (Cimadomo D, et al. 2023). However, for younger women (under 35), the clear benefit of PGT-A in improving cumulative live birth rates is still debated, and it is not universally recommended (Griffin DK, et al. 2018). The overall impact on a baby arriving in your arms may not be significant for all.
Potential for False Positives/Negatives: PGT-A tests only a small portion of the embryo. This can lead to discrepancies, such as "mosaic embryos" (embryos containing both normal and abnormal cells), which present a diagnostic challenge. Consequently, there's a possibility of misclassifying an embryo as abnormal when it is actually euploid (false positive), or vice versa (false negative) (Nuñez-Calonge R, et al. 2024).
Potential Risk to Embryo: Embryo biopsy is a delicate procedure. Although rare, there is a very small, non-zero risk of causing minor damage to the embryo during the process.
Emotional and Financial Burden: PGT-A incurs additional costs, and receiving results that indicate no transferable embryos or the failure of a seemingly euploid embryo to implant can be emotionally challenging. This emotional toll is a valid part of the TTC journey.

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Key Considerations When Considering PGT-A

PGT-A can be a powerful tool, but it may not be the optimal choice for everyone. When considering this treatment, it's vital to have a thorough discussion with your fertility specialist, taking these points into account:

Consider Your Individual Circumstances: Evaluate if PGT-A is truly a beneficial option for you, based on your age, fertility history, and any history of recurrent pregnancy loss.
Understand the Pros and Cons: Fully grasp the potential benefits of the test, along with its limitations, risks, and the potential emotional and financial impact.
Compare Multiple Options: It's important to gather information and discuss PGT-A alongside other treatment strategies to determine the best path forward for your unique situation.

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Frequently Asked Questions (FAQ)

Q1: Is PGT-A recommended for all IVF patients?

A1: No, PGT-A is not universally recommended for all IVF patients. Its benefits are generally considered greater for specific situations, such as older women or those with a history of recurrent miscarriages. For younger women, its efficacy is still debated, making it crucial to discuss your individual circumstances with your fertility specialist and consider it carefully.

Q2: Does an embryo diagnosed as "normal" by PGT-A guarantee pregnancy?

A2: No. In numbers: the positive predictive value of a euploid result is no higher than 50–60% (PMID: 37192834). A "normal" result still fails to implant four to five times out of ten.

The field calls this unexplained gap "the black box of implantation."

The same review lists factors associated with euploid blastocysts still failing:

Reduced inner cell mass quality (odds ratio 0.37) or trophectoderm quality (0.53)
Blastocyst quality below Gardner BB (0.40)
Developmental delay (0.56)
Age 38 or over (0.87), obesity (live birth 0.66 / miscarriage 1.8), previous repeated implantation failure (0.72)

★Most of the included studies were retrospective or small, and the authors rate the certainty of evidence as low or very low.

★It should also be noted that the authors include staff of a company providing PGT (Juno Genetics), and several are affiliated with the IVIRMA Global Research Alliance. This conflict of interest runs in PGT-A's favour and should be kept in mind.

Q3: What are the costs associated with PGT-A?

A3: PGT-A is an out-of-pocket expense, and costs can vary significantly between clinics. Generally, you can expect additional fees for embryo biopsy and genetic analysis, often amounting to several thousand dollars. It's important to inquire about the full financial implications beforehand and make an informed decision considering the economic burden.

Summary

PGT-A is a significant adjunct technology in IVF, potentially contributing to shorter treatment times and reduced miscarriage rates, especially for older women. However, its effectiveness varies by age and individual circumstances, and it comes with inherent limitations and potential risks. While the emotional ups and downs are a natural part of this journey, making decisions based on calm, objective information is paramount. Do not be swayed by unverified claims; always engage in a thorough discussion with your fertility specialist to determine the most suitable treatment plan for you.

References

Cimadomo D, et al. "Opening the black box: why do euploid blastocysts fail to implant? A systematic review and meta-analysis." Hum Reprod Update. 2023. PMID: 37192834 (★the authors include staff of Juno Genetics, a company providing PGT, and several are affiliated with the IVIRMA Global Research Alliance; this conflict of interest is disclosed. ★Most included studies were retrospective or small, and the authors rate the certainty of evidence as low or very low)
Nuñez-Calonge R, et al. "Making and Selecting the Best Embryo in In vitro Fertilization." Arch Med Res. 2024. PMID: 39191078
Griffin DK, et al. "Chromosomal analysis in IVF: just how useful is it?" Reproduction. 2018. PMID: 29945889 (★a narrative review; the authors themselves ask when we should consider the evidence base sufficient to justify routine PGT-A)

Written by the same author — a general guide to preconception care and fertility planning: https://www.amazon.com/dp/B0F771VNV5?tag=ttcguide-enblog-22