Miscarriage. For too many women, this word lays heavy, bringing a flood of emotion that is all encompassing: sorrow, shock, confusion, guilt. If you have not experienced a miscarriage, there is a good chance you know someone who has; with 1 in 4 pregnancies ending in loss, this has almost certainly impacted you or someone you love.
However, in the past 15 years, a technology called preimplantation genetic testing for aneuploidy, or PGT-A, has been shown to help reduce the likelihood of miscarriage1,2 in those pursuing in vitro fertilization (IVF). This testing may bring new hope to those trying to conceive after loss, as well as those who may be just beginning their journey to parenthood.
While no method of assisted reproductive technology (ART), including IVF, or genetic testing, guarantees achieving or sustaining a healthy pregnancy, data collected from samples tested at CooperGenomics from 2010-2012 and 2014-2016 has shown that the addition of PGT-A in an IVF cycle can lower the risk of miscarriage1,2.
When and Why Do Miscarriages Occur?
Miscarriage may occur at any time during pregnancy, but approximately 80% of losses occur in the first trimester3 (before 13 weeks of pregnancy). There are many reasons for pregnancy loss, and in some cases, one specific cause is not identified. However, at least 50% of first trimester miscarriages are the result of a chromosome abnormality in the developing baby3.
What is a Chromosome Abnormality?
Let’s revisit high school biology. Chromosomes are the structures that carry our genetic material; they contain the instructions for appropriate growth and development. Most individuals have 46 chromosomes in each cell of their body. Chromosomes are inherited in pairs; one copy of each pair comes from the egg and one copy of each pair comes from the sperm. These combine and create the embryo that develops into a baby.
The first 22 pairs of chromosomes (the autosomes) are the same in males and females. The 23rd pair of chromosomes is the sex chromosomes. Individuals with two X chromosomes are chromosomally female. Individuals with one X and Y chromosome are chromosomally male.
Any time an embryo is conceived, whether in a spontaneous pregnancy or as part of an IVF cycle, there is a risk the embryo will have an incorrect number of chromosomes. This may be too few chromosomes (referred to as monosomy), too many chromosomes (referred to as trisomy), or missing or extra pieces of chromosomes (referred to as partial monosomy/trisomy).
Most chromosome problems are not inherited4; they occur by chance alone. Importantly, the risk to conceive an embryo with a chromosome problem increases as women age4, but all embryos have a baseline risk of having an incorrect number of chromosomes, regardless of the age of the mother or egg donor.
If an embryo with an incorrect number of chromosomes implants, and pregnancy begins, most of the time, the pregnancy will end in a miscarriage4.
How Does PGT-A Help Identify Embryos at Higher Risk of Miscarrying?
While nothing prevents spontaneous chromosome abnormalities from occurring, screening is available to help identify these issues. You may already know that evaluation for chromosome abnormalities is available during pregnancy, but did you know testing is available before pregnancy?
For women who are completing a cycle of IVF, it is possible to screen embryos for chromosome abnormalities prior to transfer using PGT-A technology.
For this evaluation, a small sample of cells (a biopsy) is taken from the outer layer, or trophectoderm, of each embryo. These cells are then analyzed to determine the apparent number of chromosomes present.
Current testing identifies whole chromosome gains, whole chromosome losses, and gains and losses of large pieces of chromosomes. In most cases, PGT-A provides one of three results:
- The embryo sample has the correct number of chromosomes; this is identified as euploid.
- The embryo sample has an incorrect number of chromosomes; this is identified as aneuploid.
- The embryo sample is identified as mosaic; meaning some of the tested cells had the correct number of chromosomes and others had an incorrect number of chromosomes. Mosaic results may be difficult to interpret and the decision to transfer (or not transfer) these embryos may be challenging.
Whatever the result may be, genetic counseling is always available to help you understand your PGT-A result(s).
The results of many PGT-A tests are typically greater than 97% accurate5, and, most importantly, they are actionable! After reviewing your PGT-A results with your doctor, the two of you may work together to prioritize embryos for transfer.
Embryos identified as euploid have an increased chance of implantation when compared to mosaic and aneuploid embryos6,7. In addition, pregnancies conceived after the transfer of a euploid embryo have a significantly lower risk of miscarriage when compared to mosaic and aneuploid embryos6,7.
How do I find out more about PGT-A?
The impact of pregnancy loss is significant; the emotional toll one or more miscarriages may have on a woman and/or a couple is profound. However, there are options available that may be able to lower your risk of miscarriage, including screening options before and during pregnancy.
If you are currently considering a cycle of IVF, you may wish to talk with your doctor about PGT-A to determine if it may help you achieve a chromosomally healthy pregnancy and reduce your risk of miscarriage. It is important to make the decision that is ultimately right for you and your family. CooperGenomics wishes you the best on your journey to parenthood.
1Grifo, J.A., et al., Single thawed euploid embryo transfer improves IVF pregnancy, miscarriage, and multiple gestation outcomes and has similar implantation rates as egg donation, Journal of Assisted Reproduction and Genetics, 2013. 30(2): p. 259-264.
2 Friedenthal, J., et al., Next generation sequencing for preimplantation genetic screening improves pregnancy outcomes compared with array comparative genomic hybridization in single thawed euploid embryo transfer cycles, Fertility and Sterility, 2018. 109(4): p. 627-632.
3American College of Obstetricians and Gynecologists. “Early Pregnancy Loss.” ACOG, 29 Aug. 2018, www.acog.org/Clinical-Guidance-and-Publications/Practice-Bulletins/Committee-on-Practice-Bulletins-Gynecology/Early-Pregnancy-Loss.
4McKinlay Gardner RJ and Sutherland GR. Chromosome Abnormalities and Genetic Counseling, 3rd edition. Oxford, Oxford Press, 2004.
5J. Friedenthal, S.M., et al., Clinical error rates of next generation sequencing and array comparative genomic hybridization with single thawed euploid embryo transfer, European Journal of Medical Genetics (2020).
6Victor AR, et al. One hundred mosaic embryos transferred prospectively in a single clinic: exploring when and why they result in healthy pregnancies, Fertility and Sterility, 2019. 111(2): p. 280-293.
7Munne S., et al., Detailed investigation into the cytogenetic constitution and pregnancy outcome of replacing mosaic blastocysts detected with the use of high-resolution next-generation sequencing, Fertility and Sterility, 2018. 108(1): p. 62-71.