To test or not to test?

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Last December, the NYTimes published an opinion piece titled The Big IVF Add-on Racket, which criticized the widespread use of “add-ons” in fertility care. An add-on is anything that is considered non-essential to carry out an IVF cycle. Examples include Co-Q10, endometrial scratching, assisted hatching, and human growth hormone. 

An add-on is typically offered with a statement like, “We also offer X treatment, which may improve your chance of pregnancy. Would you like to try it?”. But, the benefit of the treatment is often unclear and the out-of-pocket cost can be quite high leaving many patients feeling confused and burdened by the decision. 

The most common and most expensive add-on that I hear patients struggling with is preimplantation genetic screening. So this post will address the current evidence supporting the use of preimplantation genetic screening and how you might think about it in the context of your own care. (You may have also heard it called PGS, CCS, or PGT-A. All refer to the same thing. I will use PGT-A here as it is the most current acronym used by the field.)

What is PGT-A testing?

PGT-A assesses the number of chromosomes in an embryo. Human cells should have 23 specific pairs of chromosomes. For all couples, not just those struggling with infertility, abnormalities in the number or pairings of these chromosomes is one reason it can take many months to get pregnant and 20% or more of pregnancies end in miscarriage. In women younger than 35, between 30 and 50% of embryos have these abnormalities and this increases with age to a rate of 80% in those over 42 (1). So, the idea is that PGT-A helps select chromosomally normal embryos for transfer, decreasing the chance of a failed embryo transfer or miscarriage.

But does it work? 

A handful of relatively small studies have shown increased pregnancy and birth rates following the use of preimplantation genetic screening (2,3), particularly for women in their late 30’s and early 40’s (4). However, a recent large, multi-center, randomized controlled trial - the gold standard in clinical research - only found an improvement in on-going pregnancy rates using PGT-A for women older than 35 (1).

So, as is often the case in infertility, there is not a lot of clear data. However, just because the most recent study used the “gold standard” design, doesn’t necessarily mean its findings are conclusive. In fact, the authors admit a few challenges. First, it was a multi-center study, which is a good thing. But, each center used its own lab, which used different criteria and protocols for evaluating and testing embryos. This was intentional, the authors wanted to represent the efficacy of PGT-A “in the real world”. But, the variation in lab protocols may have masked beneficial effects of PGT-A. In addition, the study focused on “good prognosis” patients, excluding those with diminished ovarian reserve, more than 2 failed IVF embryo transfers, or more than one miscarriage. So, PGT-A testing may still be beneficial in more challenging cases.  

So, how might I think about PGT-A in the context of my care? 

First, there is one more thing to understand about PGT-A testing. The test involves take a biopsy from each embryo tested. To do this, a few cells are removed from the outer part of the embryo that will become the placenta. This ensures that the inner part of the embryo that will develop into the baby isn’t harmed by the test. But, placental cells are known to have high rates of chromosomal abnormalities that don’t necessarily affect the developing embryo. This means that some embryos with abnormal PGT-A results can develop into healthy newborn babies (4,5). What this means is that PGT-A is a rule in test not a rule out test. It tells you which embryos definitely have the correct number of chromosomes and, therefore, are more likely to lead to a successful embryo transfer and pregnancy. But the test may label some embryos as abnormal even though a normal, healthy baby could develop from them. 

So, PGT-A can help you prioritize which embryos to transfer first. This may reduce the number of embryo transfers you need to do to achieve a successful pregnancy. If you are feeling the emotional, personal, and physical burden of repeated treatments, this may be a reason to consider PGT-A testing.

But, PGT-A doesn’t affect your overall chance of a successful pregnancy. It may simply help you get to success sooner. And, the test is expensive. So, opting out is OK and not a medically irresponsible decision.

Finally, it is important to keep in mind that even a PGT-A normal embryo may fail to implant or lead to a miscarriage. There are countless factors that affect embryo development from the uterine environment to genetic abnormalities not identified by the PGT-A test.

The bottom line is that the decision to use PGT-A testing is highly personal and depends on your clinical, emotional, and financial situation. There is no right or wrong answer and it is your choice to make. You shouldn’t feel pressured into a decision. But, as the NYTimes article points out, the decision can feel overwhelming. 

So, if your doctor offers PGT-A testing, be sure to ask why he or she feels it would be beneficial for you specifically. If their answer isn’t satisfying, consider seeking a second medical opinion. Or consider talking to a patient advocate or coach specialized in infertility to support you through the decision process. If you would like to discuss this or any other challenging decision you are faced with on your fertility journey, don’t hesitate to reach out.

I hope you find this helpful. Feel free to email me with follow-up questions. To receive more content like this, sign-up here.

  1. Munné S, Kaplan B, Frattarelli JL, et al. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019;112(6):1071-1079.e7. doi:10.1016/j.fertnstert.2019.07.1346

  2. Yang, Z., Liu, J., Collins, G.S. et al. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet 5, 24 (2012). https://doi.org/10.1186/1755-8166-5-24

  3. Scott RT Jr, Upham KM, Forman EJ, et al. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013;100(3):697-703. doi:10.1016/j.fertnstert.2013.04.035

  4. Rubio C, Bellver J, Rodrigo L, et al. In vitro fertilization with preimplantation genetic diagnosis for aneuploidies in advanced maternal age: a randomized, controlled study. Fertil Steril. 2017;107(5):1122-1129. doi:10.1016/j.fertnstert.2017.03.011

  5. Greco E, Fiorentino F. Healthy babies after intrauterine transfer of mosaic aneuploid blastocysts. N Engl J Med 2015; 373:2089-2090 DOI: 10.1056/NEJMc1500421

  6. Hong B, Hao Y. The outcome of human mosaic aneuploid blastocysts after intrauterine transfer: A retrospective study. Medicine (Baltimore). 2020;99(9):e18768. doi:10.1097/MD.0000000000018768

Stephanie Wissig