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Unless you’ve been a part of the TTC community for a while, you may not have heard of one of the less obvious causes of infertility: a genetic condition called a balanced translocation (also referred to as reciprocal translocation).
Balanced Translocation affects approximately 1 in 500 people. However, in those with recurrent pregnancy loss, it has been shown to be substantially higher at 3 – 7%. When either partner has a translocation, the risk of miscarriage increases from 20% to approximately 40%.
The frustrating part is that the majority of people with a balanced translocation have no major health concerns and are unaware that they even have this condition; it usually only becomes apparent in the setting of trying to conceive. The ‘typical’ presentation is a couple who has unfortunately had multiple pregnancy losses, and their basic infertility workup assessing the egg and sperm health is normal.
So, what is balanced translocation?
An individual’s genetic makeup is comprised of 23 pairs of chromosomes that are roughly X shaped. When a person’s cells divide to create gametes (eggs or sperm), the chromosome should divide in half symmetrically allowing equal portions of the genetic material to be divided into the cells. However, things don’t always go according to plan during this division process, and rearrangements happen. Once fertilization occurs, the matching chromosomes from the sperm and the egg rejoin and create a single chromosome again.
By definition, a balanced translocation is when part of one chromosome breaks off and attaches to a different chromosome. A common analogy used to describe this is to imagine you have two large bows that are different colors. Then imagine that you cut a small section from the short arm of each bow, switch places, and then tie them back together. You would then still have two intact bows, but part of each bow is a different color. A balanced translocation essentially is a portion of the genetic material switching spots. The total number of chromosomes and genetic material remains intact, but the structure of the chromosome is broken because a portion of the chromosome is attached incorrectly.
People that carry a balanced translocation can create embryos that either have the same balanced translocation, an unbalanced translocation (where there is gain or loss of genetic material), or a normal set of chromosomes that are completely unaffected. Typically, a balanced translocation and a normal set of chromosomes will allow for normal embryo development and live birth. However, an unbalanced translocation will typically result in pregnancy loss. Research has shown that if one partner is a carrier of a balanced translocation, approximately 75% of the embryos will have an abnormal genetic makeup.
How is balanced translocation diagnosed?
A balanced translocation is diagnosed through a blood test called a karyotype or chromosomal analysis. A blood sample is drawn from both partners, which is then analyzed in the lab to assess the number and appearance of each chromosome. If a balanced translocation is found, the report will identify the chromosomes that are affected and where on those chromosomes the switching of genetic material can be found.
Balanced Translocation and IVF
Unfortunately, there is no way to cure a balanced translocation, as it is just a part of the individual’s unique genetic makeup. But with the current technology, recurrent pregnancy loss due to balanced translocation can be overcome through In Vitro Fertilization (IVF) and Preimplantation Genetic Testing for Structural Rearrangements (PGT-SR).
The most commonly used technique for PGT-SR is Next Generation Sequencing (NGS). The goal of PGT-SR is to determine which embryos contain the correct amount of genetic material (balanced translocation or a normal number of chromosomes) and rule out the embryos that have an incorrect amount of genetic material (unbalanced translocation). By identifying the embryos that have an unbalanced translocation, PGT-SR can reduce the likelihood of miscarriage.
The technology has evolved over the past few years, and a few select labs can now make the distinction between those embryos that carry the balanced translocation and those embryos that are considered unaffected by the translocation (normal). This technology is referred to as PGT-SR plus and uses a combination of NGS and Single-Nucleotide Polymorphism (SNP) microarray.
What does the process entail?
While all of this may seem complicated, IVF with PGT-SR requires no additional work from you. Prior to starting the IVF process, the PGT lab will conduct a case review of your translocation to ensure that they have all the appropriate information needed to perform PGT-SR. Most PGT companies also have you meet with a genetic counselor to provide more information about your balanced translocation and how it can affect the outcome of IVF with PGT-SR. Once the case has been approved by the PGT lab, the IVF process begins.
IVF is a sequence of highly coordinated steps beginning with controlled ovarian hyperstimulation. This involves daily injections of medication to allow for the growth of egg-containing follicles on the ovary of the female partner for approximately 8 – 14 days. The retrieval of the eggs is timed using a special injection called a trigger. The eggs are then removed from the ovaries under transvaginal ultrasound guidance (no incisions required), and fertilization between the eggs and sperm occurs in the lab.
The day of the egg retrieval is considered day 0. Embryo(s) are then incubated until they have reached the blastocyst stage (day 5 or day 6) when the viable embryos are biopsied. The biopsy involves taking a small sample of cells from the outer edge of the embryo called the trophectoderm. Thankfully, removing cells from this area of the embryo does not affect the development of the fetus as the cells from the trophectoderm are predetermined to develop into the placenta. The biopsied embryos are then frozen and the cell samples from each embryo are analyzed at a PGT lab. Using NGS technology, the PGT lab is able to determine if the embryo is affected by an unbalanced translocation.
Once the balanced/normal embryos have been identified via PGT-SR, the embryos are then assessed for aneuploidy via Preimplantation Genetic Testing for Aneuploidy (PGT-A) which screens for absence or gain of entire chromosomes. The turnaround time for test results varies between PGT labs, but most companies guarantee results within 10 days. The report will be sent to your physician and reviewed with you to determine the best embryo available for your frozen embryo transfer.
The good news is, if you’ve suffered multiple miscarriages or have been recently diagnosed with a balanced translocation, there are options available to you. While no amount of technology can take away the heartache you’ve endured to get to this point, karyotype testing can work to diagnose a balanced translocation, and IVF with PGT-SR can help identify which embryos offer you the best possible chance at a healthy pregnancy. And that is something to celebrate.
Jessica Boone, MPA, PA-C is a Physician Assistant who has been practicing in Reproductive Endocrinology and Infertility for her entire 9-year career. She believes that knowledge is power when it comes to fertility, and the journey to building a family is challenging enough without a good understanding of the process.
