Is preimplantation genetic testing for aneuploidy (PGT-A) an essential tool for embryo selection or costly 'add-on' of no clinical benefit?

Fertile Battle

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Volume 110, Issue 3, Pages 351–352

Authors:

Zev Rosenwaks, M.D., Alan H. Handyside, Ph.D.

Abstract:

Chromosome aneuploidy is common in human gametes and preimplantation embryos and is a major cause of in vitro fertilization (IVF) failure, miscarriage, and still births, with an incidence at birth of less than 0.3%. Most aneuploidies originate in the oocyte through errors in maternal meiosis and these increase exponentially in women in their late 30s and early 40s. This is associated with a sharp increase in the incidence of miscarriage and a corresponding decline in live birth rates in these women following IVF.


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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

6 Comments

Go to the profile of Kurt Barnhart
Kurt Barnhart over 1 year ago

Great debate, Please add you comment and vote!


Go to the profile of Micah J Hill
Micah J Hill over 1 year ago

Good debate!  We've been somewhat slow adopters of PGT-A, using it in around 10% of our cycles, mainly because it adds more than 50% to the cost for military couples to do IVF in our center.  We also have had a single embryo transfer policy for good prognosis patients for the past 10 years.  So while the use of PGT-A hasn't effected our singleton rate much, it has helped to further increase our success in SET cycles.  Its also been very helpful in our older patients with good ovarian reserve, who make a lot of embryos but have a high aneuploidy rate.  It definitely decreases time to live birth and miscarriage risk in these patients.

Up vote from me!

Go to the profile of Jason Franasiak
Jason Franasiak over 1 year ago

Great debate! The drop out rate for failed IVF cycles is significant and may lead couples to stop seeking care which ultimately decreases the chance for conception due to simply drop out rate. With the sensitivity and specificity of PGS at rates that we see it makes sense to think about this as an approach to care.

Go to the profile of Rani Fritz
Rani Fritz over 1 year ago

Great debate! Here are my two cents and vote (or five cents based on the length of this response).

As with many debates in medicine there is value on both sides of the argument. I think there is no universal right or wrong answer for the use of PGT-A, and whether to perform PGT-A is ultimately the patient’s decision and should be guided by a thorough counseling session discussing the pros and cons of the procedure taking into consideration each patient’s unique circumstance. For example, in a young patient with good ovarian reserve generating multiple blasts, PGT-A has proven to decrease the time to pregnancy, decrease miscarriage rates, and prioritize an embryo for SET decreasing multiple rates. Discussion with the patient relating to the pros (above) versus main drawbacks including cost and need for FET (although many would argue is a plus- another debate), should be discussed with the patient. As Micah wrote, for “older” patients with good ovarian reserve and response that will generate many blasts that will likely have high embryo aneuploidy rates, it certainly could be of benefit in selecting a single euploid embryo for transfer from a cohort of multiple aneuploid embryos. It's the older patients with poor ovarian reserve and response (generate 1-3 blasts) where this procedure, in my opinion, could be detrimental to her goal of achieving a live born healthy infant. What would be more devastating then transferring an aneuploid embryo (which has been done for years prior to PGT-A), would be discarding an embryo that has the chance to develop into a healthy live born baby and may be the patient’s only chance to parenthood. And although true, only a handful of anecdotal cases exist of transfer of aneuploid embryos that result in healthy euploid fetuses, the true false positive rates of PGT-A is tough to estimate because not many patients and practitioners are willing to transfer aneuploid embryos and therefore most are discarded. I think the pros and cons of PGT-A in this “older” population with poor reserve and response should be discussed with the patient to help guide their decision. If an older patient with poor ovarian reserve can only undergo 1 IVF cycle, perhaps performing PGT-A would not be optimal in this situation. For all patients that desire PGT-A, and particularly in “older” patients with poor ovarian response, a discussion of what to do in the event that only mosaic embryos exist should be discussed prior to the onset of the cycle. Another thought is deciding whether to perform PGT-A based on the number of blasts generated, similarly to how some programs decide to transfer on day 3 or 5 based on how many 2PNs are generated. As a side note- according to the latest data from the CDC (2015), only 5% of cycles in the U.S. are PGD/PGT-A cycles. My vote is that there is value to PGT-A, but ultimately it should be the patient’s decision after thorough counseling of the pros and cons taking into consideration each patient’s unique circumstances. 

Go to the profile of Alexander Quaas
Alexander Quaas over 1 year ago

This "fertile battle" is yet another great debate about the value of PGT-A, this time in print- many of us have witnessed fascinating live debates at meetings between some of the authors in this piece.

The problem for me is this (maybe other readers can relate): prior to every debate I have high hopes to have a more clear-cut opinion about the issue, just to experience the exact opposite, namely an increasingly complex view of the topic afterwards. As the lively and heated debate between very smart people proves, this is not a black-and-white issue, but rather "50 shades of gray". 

Therefore my vote goes to "it depends". There is no doubt in my mind that PGT-A is beneficial when a patient who would have otherwise insisted on transferring two embryos agrees to a single (euploid) transfer. The perinatal benefits of a sET strategy are well-documented, and if PGT-A helps increase sET rates then it will be beneficial. In other clinical scenarios, the value of PGT-A is less clear-cut. Promises of PGT-A are a decrease in the time to pregnancy by improved selection in younger patients, and a decrease in potentially devastating miscarriages in women of advanced reproductive age.

The big question in my mind going forward is: how will this debate be settled? So my question for everyone on this forum is: what kind of trial(s) do we need to further assess the value of PGT-A? What should the trial design be?     

Go to the profile of Mary Samplaski
Mary Samplaski over 1 year ago

While I am an Andrologist, and not actually in the IVF lab... based on my knowledge, the answer is... in some situations. Not every IVF cycle needs PGT... but in women of AMA, second-IVF cycles, or poor embryo progression... yes, I believe there is a role. It is not a perfect technology, but it does provide more information, which can guide couples to their best embryo.