Should You Test Your IVF Embryos? The Pros, Cons, and Controversies of PGT-A

Sarah was staring at the numbers on the paper her reproductive endocrinologist had just handed her. At 35, after two years of trying to conceive, she'd finally completed her first IVF cycle. The embryologist called with news: five blastocysts had developed. Now she faced a crucial decision.

"Should I genetically test my embryos before transfer?" she asked her doctor.

The question isn't simple. On one hand, preimplantation genetic testing for aneuploidy (PGT-A) promised to improve her chances by selecting chromosomally normal embryos. On the other hand, it would add $5,000 to her already substantial IVF costs.

"I just want the best chance for a baby," Sarah said. "Is PGT worth it?"

This question confronts thousands of IVF patients annually, yet the answer remains surprisingly complex. Despite becoming nearly standard practice at many clinics—with testing rates increasing from 13% in 2014 to over 40% in 2021—the impact of PGT-A on take-home baby rates continues to spark debate among experts.

What Exactly Is PGT-A?

PGT-A is a screening procedure that examines embryos for chromosomal abnormalities before they're transferred to the uterus during IVF. The process involves:

1. Growing embryos to the blastocyst stage (day 5-7 after fertilization)

2. Removing 5-10 cells from the trophectoderm (the outer layer that will become the placenta)

3. Analyzing these cells to count chromosomes

4. Classifying embryos as euploid (normal chromosome count), aneuploid (abnormal count), or mosaic (mixed cells)

The goal is simple: identify embryos with the correct number of chromosomes (23 pairs), which are more likely to implant successfully and develop into healthy pregnancies.

A common misconception is that PGT-A is a comprehensive "DNA test." This isn't accurate. PGT-A specifically counts chromosomes—the packages that contain genes—rather than analyzing the actual genetic code within them.

"It's like counting how many books are on a shelf, not reading what's inside them," explains Dr. Richard Scott, a reproductive endocrinologist and researcher. "PGT-A tells us if there are too many or too few chromosomes, not whether the genes themselves have mutations."

Originally called PGS (Preimplantation Genetic Screening), the technology has evolved significantly over the years, leading to its rebranding as PGT-A in 2016 to better reflect its specific focus on aneuploidy.

The Technology Behind the Test

The accuracy of PGT-A has improved dramatically with technological advances. Today's methods are substantially more reliable than earlier techniques.

Evolution of PGT-A Technologies:

1. FISH (Fluorescence In Situ Hybridization): The original method tested only 5-9 chromosomes with false positive rates as high as 15-20%. A landmark 2007 study by Mastenbroek et al. in the New England Journal of Medicine actually showed decreased pregnancy rates with this method.

2. aCGH (Array Comparative Genomic Hybridization): Introduced around 2010, this technique tested all 23 chromosome pairs with false positive rates of 8-15%.

3. NGS (Next Generation Sequencing): The current gold standard, with false positive rates of 4-10% and much better ability to detect mosaicism.

"The shift to NGS wasn't just incremental—it fundamentally changed what we could detect," says Dr. James Grifo, Program Director at NYU Langone Fertility Center. "Now we can identify mosaic embryos, which fall between normal and abnormal, opening up new possibilities for patients."

NGS works by fragmenting the DNA from biopsied cells and sequencing millions of fragments simultaneously. These sequences are compared to reference standards to determine if chromosome quantities are normal. The process is remarkably sensitive but not infallible.

A 2018 study in the journal Fertility and Sterility by Tiegs et al. reported that modern NGS technology has approximately a 2% technical error rate, a significant improvement over earlier methods.

Who Benefits Most? A Patient's Guide

The potential benefit of PGT-A varies significantly depending on patient characteristics. Understanding your specific situation is crucial to making an informed decision.

The most important factor is maternal age, which strongly correlates with aneuploidy rates:

These statistics come from a comprehensive 2017 study by Franasiak et al. in Fertility and Sterility that analyzed over 15,000 embryos.

Advanced Maternal Age (>35)

For women over 35, PGT-A offers the clearest potential benefit. A 2019 randomized controlled trial by Munné et al. published in Fertility and Sterility showed that patients over 35 had significantly higher ongoing pregnancy rates per transfer when using PGT-A (51% vs. 37% without testing).

"The higher your aneuploidy rate, the more PGT-A can help by avoiding transfers that won't succeed," explains reproductive endocrinologist Dr. Aimee Eyvazzadeh.

Recurrent Pregnancy Loss

For patients with a history of miscarriages, PGT-A may help identify chromosomal issues causing losses. A 2018 study by Murugappan et al. in Human Reproduction showed that patients with recurrent pregnancy loss had improved live birth rates after PGT-A screening compared to expectant management.

Previous Failed Transfers

After multiple unsuccessful embryo transfers with good-quality embryos, PGT-A might identify hidden chromosomal issues. However, a 2019 study by Zimmerman et al. showed mixed results in this population, suggesting other factors should be investigated alongside aneuploidy.

Fertile Younger Women

The benefit is less clear for women under 35 with no history of losses or failures. A randomized controlled trial by Yang et al. (2018) found no significant improvement in cumulative pregnancy rates for women under 35, though time to pregnancy was shorter with PGT-A because couples can choose the higher quality embryos.

The Accuracy Question

Understanding the limitations of PGT-A is essential for making an informed decision. Two key concepts are false positives and false negatives:

False Positives: When a normal embryo is incorrectly identified as abnormal. This is the more concerning error for most patients, as it could lead to discarding potentially viable embryos.

False Negatives: When an abnormal embryo is incorrectly identified as normal. This could lead to transferring an embryo that may not implant or might result in miscarriage.

With modern NGS technology, false positive rates range from 4-10%, while false negative rates are approximately 2-5%, according to a 2020 systematic review by Popovic et al. in Human Reproduction Update.

The Sampling Dilemma: A Fundamental Limitation

One crucial limitation of PGT-A testing often goes unexplained to patients: the cells being tested aren't actually from the part of the embryo that will become the baby.

"Think of a blastocyst embryo like a water balloon with a small cluster of cells stuck to the inner wall," explains Dr. Maria Chen, embryologist at Pacific Fertility Center. "The outer balloon layer—called the trophectoderm—will become the placenta. The small inner cluster—called the inner cell mass—will develop into the baby. PGT-A only samples cells from the outer balloon layer."

This creates an inherent accuracy problem. Since the test examines future placental cells, not future fetal cells, it's essentially making an educated guess about the baby's chromosomes based on its placenta's chromosomes. These don't always match.

A 2020 study by Victor et al. in Fertility and Sterility found that up to 18% of embryos showed different chromosomal patterns between these two cell groups. This phenomenon, called "embryo mosaicism," means the sample might not represent what's actually happening in the critical inner cells.

"It's like trying to determine if there's a problem with the engine by only looking at the car's exterior," says Dr. Chen. "Usually, it works as an indicator, but sometimes you get it wrong."

This explains why some embryos labeled "abnormal" can result in healthy births, while others deemed "normal" fail to develop. The biopsy simply didn't capture the true chromosomal makeup of the cells that matter most.

Jennifer's story illustrates the implications of these errors. After her first IVF cycle at 38, all five of her embryos tested aneuploid. Devastated, she sought a second opinion at a clinic that offered aneuploid embryo transfers under certain circumstances.

"If I had stayed at my first clinic, those embryos would have been discarded," she explains. "Instead, I transferred one that had a single chromosome abnormality, and today she's my three-year-old daughter."

Dr. Norbert Gleicher of the Center for Human Reproduction has published extensively on this topic. In a 2017 paper in the Journal of Assisted Reproduction and Genetics, he notes: "The clinical utility of PGT-A is limited by the inherent invasiveness of the procedure and the imperfect correlation between the genetic makeup of trophectoderm and inner cell mass."

Simply put, the few cells we test might not perfectly represent the entire embryo. The best way to use GPT-A then might be just to see it as another grading system, instead of a yes or no destiny for the small embryo that’s still under early development stage.

The Aneuploid Transfer Revolution

One of the most significant shifts in recent years has been the willingness of some clinics to transfer embryos that PGT-A identifies as abnormal or mosaic.

This practice emerged after several striking discoveries:

1. Some embryos can "self-correct" chromosomal abnormalities during development

2. The trophectoderm (biopsied area) may not always reflect the inner cell mass (future baby)

3. Healthy births have resulted from transfers of embryos previously labeled as abnormal

Dr. David Barad, who has studied this phenomenon, explains: "We've seen that some embryos have remarkable resilience and can overcome certain chromosomal issues."

Not all abnormalities are equal, however. The specific chromosome affected dramatically impacts potential outcomes:

More Compatible with Life:

• Mosaic embryos (20-80% abnormal cells)

• Trisomy 21 (Down Syndrome)

• Sex chromosome abnormalities (XXY, XYY, XXX)

• Some segmental abnormalities (partial deletions/duplications)

Generally Incompatible with Life:

• Most monosomies (except Monosomy X)

• Trisomies of chromosomes 1, 2, 3, 5, 6, 16, 17, 19

• Complex aneuploidies (multiple chromosomes affected)

A groundbreaking 2020 study by Viotti et al. in Fertility and Sterility reported live births from the transfer of mosaic embryos with success rates of approximately 30-40% compared to 50-70% with euploid embryos.

Lisa's story represents this new frontier. After being told all her embryos were abnormal at age 41, she chose to transfer a mosaic embryo with a partial chromosome deletion. "It was a difficult decision that required extensive counseling," she recalls. "But that embryo is now my son. The abnormality wasn't detected in his cells after birth."

Making Your Decision

Given all this information, how should you decide about PGT-A? The decision framework should consider:

Age

• Under 35: Benefits less clear, consider banking embryos first

• Over 35: Stronger case for testing

• Over 40: Benefits typically outweigh drawbacks for most patients

Number of Embryos

• Few embryos (<3): Testing risks having none to transfer

• Many embryos (>5): Testing helps prioritize transfers

Financial Situation

• Testing adds $3,000-7,000 to IVF costs

• Not typically covered by insurance

• Cost-effectiveness improves with age

Risk Tolerance

• For miscarriage: Testing reduces risk

• For discarding viable embryos: Consider clinic policies on mosaic/aneuploid transfers

Previous Pregnancy History

• Recurrent loss: Testing may identify causes

• Failed transfers: May benefit from testing

• Previous chromosomal issues: Stronger case for testing

The Future of Embryo Selection

The field continues to evolve rapidly, with several promising developments on the horizon:

Non-Invasive PGT-A Researchers are developing methods to test for chromosomal abnormalities without embryo biopsy by analyzing DNA released into culture media. A 2019 study by Rubio et al. in Fertility and Sterility showed promising concordance between traditional biopsy and non-invasive methods.

Artificial Intelligence in Embryo Selection AI algorithms can assess embryo morphology and development patterns to predict viability. A 2019 study by Tran et al. demonstrated that AI could identify embryos with high implantation potential based solely on images.

Comprehensive Genetic Analysis Beyond chromosomal counting, more detailed genetic analysis is becoming feasible. A 2021 paper by Treff et al. in Fertility and Sterility described methods to simultaneously screen for aneuploidy and hundreds of single-gene disorders.

Dr. Dagan Wells, a leading researcher in reproductive genetics, predicts: "Within five years, we'll likely have non-invasive methods that provide more genetic information with less risk to the embryo."

Beyond the Binary

As for Sarah, it's clear that PGT-A decisions aren't simply yes or no. After careful consideration of her age, embryo count, and personal preferences, she opted to test three embryos and leave two untested.

"I wanted some assurance but didn't want to risk losing viable embryos to false positives," she explains. Her first transfer of a euploid embryo was successful, resulting in her daughter Emma. The remaining embryos remain frozen for potential future use.

The field needs to move away from binary thinking about embryos as simply "good" or "bad." Dr. Santiago Munné, a pioneer in preimplantation genetics, observes: "We're entering an era of more nuanced, personalized approaches to embryo selection that consider multiple factors beyond chromosomes."

For patients navigating IVF decisions, understanding the science, benefits, and limitations of PGT-A empowers them to make choices aligned with their unique circumstances and values. The right decision isn't universal—it's personal.

Some Extra Notes For You: Understanding Your PGT-A Report

PGT-A reports classify embryos into categories:

• Euploid: Normal chromosome count (46,XX for female or 46,XY for male)

• Aneuploid: Abnormal chromosome count (e.g., 47,XX+21 indicates an extra chromosome 21)

• Mosaic: Mixture of normal and abnormal cells (e.g., mos 46,XY/47,XY+16 indicates some cells have an extra chromosome 16)

• Segmental: Part of a chromosome is duplicated or deleted (e.g., 46,XX,del(4)(q28) indicates deletion on chromosome 4)

Reports typically include the percentage of abnormal cells for mosaic embryos and may rank them by reproductive potential.

Mosaic Embryos: The Grey Area of Testing

Mosaicism occurs when an embryo contains both normal and abnormal cells. Key facts:

• Found in approximately 20% of blastocysts

• Transfer success rates: ~30-40% (vs. 50-70% for euploid)

• Lower percentages of abnormal cells (20-40%) have better outcomes

• Different chromosomes have different impacts on development

• Guidelines from PGDIS (Preimplantation Genetic Diagnosis International Society) provide hierarchical recommendations for which mosaic embryos to consider for transfer

Cost Breakdown: What You're Paying For

PGT-A testing typically costs $3,000-7,000 depending on embryo numbers. This includes:

• Embryo biopsy ($1,500-2,500)

• Genetic analysis ($250-500 per embryo)

• Genetic counseling ($200-400)

• Extended embryo culture and freezing (often required with testing)

Insurance coverage varies widely by state and provider, with only a few states mandating coverage for genetic testing of embryos.