ASRM’s 2024 committee opinion on the use of PGT-A

The ASRM has released their 2024 committee opinion on the use of PGT-A, covering the use of PGT-A for patients with a good prognosis, advanced age, donor eggs, recurrent pregnancy loss and more.

The American Society for Reproductive Medicine (ASRM) is an authority on reproductive medicine that releases committee opinions on various topics. The latest committee opinion is on the use of PGT-A.

PGT-A is a technique that involves testing the DNA of embryos to help select an embryo for transfer. Euploid embryos, with the right number/structure of chromosomes, are thought to have higher success rates and a lower chance of miscarriage.

PGT-A is often recommended for patients with recurrent losses, or for older patients. However, more recently PGT-A has been recommended routinely for all patients.

The ASRM developed this committee opinion on the use of PGT-A for various patient groups and situations.

Check out my complete guide to PGT-A to get more background on PGT-A (aka PGS testing).

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PGT-A for good prognosis patients

There have been 5 randomized controlled trials (RCTs) investigating the use of PGT-A. These studies compared outcomes after transferring a euploid vs transferring a best quality embryo (as determined by conventional grading). Here’s a brief look at these five studies:

Yang et al. (2012) used aCGH for PGT-A and found a higher pregnancy rate for a euploid vs the best quality untested embryo (70.9% vs 45.8%). There were no differences in miscarriage rates. The patients were good prognosis (<35, no previous miscarriages) and had good quality embryos.
Forman et al. (2013) used PCR for PGT-A and found no difference when transferring a euploid vs two untested blastocysts (60.7% vs 65.1%). There were no differences in miscarriage rates. The women were <43, with an average age of about 35, and had good quality embryos.
Scott et al. (2013) used qPCR for PGT-A and found improved sustained implantation after transferring a day 6 euploid vs the best untested day 5 embryo (66.4% vs 47.9%). Miscarriages rates were lower with PGT-A (8.9% vs 21.1%). Women were between 21-42, with an average age of about 32, and had good quality embryos.
Munne et al. (2019) used NGS for PGT-A and found no difference in ongoing pregnancy rates between patients who transferred a euploid or their best quality embryo. Women 25-40 were included, with an average age of 33.7, and had good quality blastocysts. Different PGT-A labs were used for testing. There were no differences in miscarriage rates. A post hoc analysis found that women aged 35-40 had an increased ongoing pregnancy rate with a euploid transfer (51% vs 37%). I reviewed this study in my post PGT-A doesn’t improve success rates in good prognosis patients.
Yan et al. (2021) used NGS for PGT-A and found no difference in cumulative live birth after up to three embryo/euploid transfers within 1 year (77.2% vs 81.8%). They found lower miscarriage rates with PGT-A (8.7% vs 12.6%). The women were between 20-37 years old, and had at least 3 good quality blastocysts. I reviewed this study in my post PGT-A vs embryo grading: results of a 2021 clinical trial.

Generally, all these RCTs were performed in patients with a good prognosis — they’re young and have good quality blastocysts. ASRM states that better RCTs are needed that investigate a broader range of patients, to see if there are benefits for the general population.

Although they don’t explicitly state it, it seems that the ASRM believes that more and better data is needed to recommend PGT-A for good prognosis patients.

PGT-A for patients with advanced age

There’s an increased risk of aneuploidy with advancing maternal age, so PGT-A may be more beneficial for these patients:

The only RCT that found a benefit for PGT-A in older patients was Munne et al. 2019 (reviewed here), which was only found in a post hoc analysis. This study used NGS and biopsied blastocysts, which is currently the standard for PGT-A.
There was an RCT by Rubio et al. (2017) that investigated PGT-A for older patients, however this was done using day 3 cleavage stage embryos. They found increases in live birth rates and lower miscarriage rates when transferring a euploid, but using cleavage stage embryos has been shown to damage the embryo, along with other disadvantages (reviewed here).
ASRM referenced several retrospective studies that have investigated PGT-A for older patients, but none of them used NGS (Whitney et al. 2016, Lee et al. 2015, Kang et al. 2016, Sacchi et al. 2019). They note a number of issues with these studies, including their retrospective design, small size and bias toward patients with a good prognosis (who had blastocysts/a lot of eggs).
Overall, ASRM states that PGT-A may be beneficial for older women with a good ovarian response.

The above was based on advanced maternal age, so what about paternal age?

A meta-analysis by Dviri et al. (2021) combined the results of 6 studies, and found that paternal age didn’t influence aneuploidy rates when using donor eggs.
Overall, the ASRM states that the evidence doesn’t support the use of routine PGT-A for patients with advanced paternal age.

PGT-A for patients using donor eggs

Donor eggs usually come from patients <35 in age, and some studies have investigated whether there’s a benefit with PGT-A or not. The potential issue is that most donor eggs are frozen, so using donor eggs for PGT-A would require two rounds of freezing and thawing (one for the eggs, and another for the embryo after PGT-A).

A number of studies were reviewed with mixed results, with some studies showing worse outcomes or no change with PGT-A and donor eggs.
One of the better designed studies (my opinion) was by Doyle et al. (2020) who compared outcomes for PGT-A or no PGT-A using the same donors. They found a median euploidy rate of 75% for donor eggs, with no differences in live birth rates for PGT-A vs no PGT-A (53.8% vs 55.8%).

Overall, the ASRM states that the evidence doesn’t support the use of routine PGT-A for patients using donor eggs.

PGT-A for patients with recurrent pregnancy loss

One of the supposed benefits of PGT-A is to reduce the chance of miscarriage by avoiding the transfer of aneuploid embryos that have a higher chance of miscarrying:

Murugappan et al. (2016) found similar pregnancy and miscarriage rates for patients with RPL, with patients in the non-PGT-A group having a shorter time to successful pregnancy. The non-PGT-A group attempted to conceive spontaneously.
Bhat et al. 2021 used the SART-CORS database and found that patients with RPL who used PGT-A had a higher live birth rate, which was more pronounced with age. However, there were no differences in miscarriage rates.

Overall, the ASRM states that there is a lack of data that shows a benefit with PGT-A for patients with RPL.

Thawing and biopsying embryos or rebiopsying embryos

Some patients have embryos frozen and then decide later on to have PGT-A on. It’s not clear if the repeated freeze/thaw cycle harms the embryo.

Bradley et al. (2017) found no differences in pregnancy rates with embryos frozen/thawed twice and then biopsied.
Neal et al. (2019) found no differences in pregnancy rates with embryos frozen/thawed twice and then biopsied.

Some patients do PGT-A, but one of their embryos might have an “inconclusive” result, or “no result,” forcing them to either transfer the embryo as is or to rebiopsy (and refreeze) it:

Cimadomo et al. (2018) found that rebiopsied embryos had a live birth rate of 38.8%. No adverse obstetric outcomes were found.
De Vos et al. (2020) found no difference in live birth rates for euploids biopsied once or twice (44.0% vs 35.0%). There were no adverse neonatal outcomes.
Parriego et al. (2019) found that rebiopsied embryos had a 38.9% pregnancy rate.
Neal et al. (2019) found a lower ongoing pregnancy rate with rebiopsied embryos (66.8% vs 50.0%).
Bradley et al. (2017) found no differences in pregnancy rates with rebiopsied embryos.

Overall, ASRM states that the data is mixed on embryos biopsied twice and that there may be a drop in success rates.

Mosaic embryo results

As far as mosaic results go, the ASRM mainly refers to their 2020 committee opinion. They mention that mosaics could have lower success rates than euploids, and that there could be variability in mosaic results, as influenced by: the NGS platform used for PGT-A, the cutoffs that are used by the PGT-A lab, the PGT-A technician and software used, and individual classification preferences from PGT-A labs.

Other ASRM committee opinions on the use of PGT-A

Day of biopsy: Blastocysts biopsied on days 5 and 6 should be prioritized over blastocysts biopsied on day 7.
PGT-M with PGT-A: More studies are needed to confirm that PGT-A is beneficial in PGT-M cycles.
Male factor infertility: Doesn’t appear to be associated with aneuploidy, and not enough evidence for using testicular sperm to improve euploidy rates.
Use of ICSI (and not conventional IVF) for PGT-A: It’s reasonable to recommend ICSI for PGT-M cases, but ICSI isn’t necessary for PGT-A.
Ethnicity: Not enough data to show that certain ethnicities have a higher rate of aneuploidy.
Obstetric or childhood outcomes: Most studies don’t show any adverse obstetric, neonatal or childhood outcomes.
Cost effectiveness: PGT-A may reduce the time to pregnancy and prevent miscarriages, but more data is needed.
Embryo damage: Blastocyst biopsy is less damaging than cleavage stage embryo biopsy, but it’s not well understood if trophectoderm biopsy can impact implantation.
Patient counseling: Before PGT-A, doctors should discuss possible outcomes of PGT-A (no result, mosaics, segmental aneuploids, misdiagnosis) and the possibility of not doing PGT-A. They should also be clear on their discarding policy for aneuploid and mosaic embryos. Genetic counselors should be made available as needed.

Conclusions

The ASRM concluded that PGT-A as a universal screening tool to improve pregnancy rates or reduce miscarriage for all patients is unproven. While earlier RCTs have shown a benefit, the two most recent RCTs have not. All these RCTs have issues, particularly in using only good prognosis patients, and better studies are needed.

Reference

Practice Committee of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Electronic address: jhayes@asrm.org. The use of preimplantation genetic testing for aneuploidy: a committee opinion. Fertil Steril. 2024 May 18:S0015-0282(24)00241-3. doi: 10.1016/j.fertnstert.2024.04.013. Epub ahead of print. PMID: 38762806.

About Embryoman

Embryoman (Sean Lauber) is a former embryologist and the founder of Remembryo, an IVF research and fertility education website. After working in an IVF lab in the US, he returned to Canada and now focuses on making fertility research more accessible. He holds a Master’s in Immunology and launched Remembryo in 2018 to help patients and professionals make sense of IVF research. Sean shares weekly study updates on Facebook, Instagram, and Reddit regularly. He also answers questions on Reddit or in his private Facebook group.