Audrey Dearing, Principal Genetic Counsellor across the Care Fertility group, explains how DNA affects fertility treatment and how we analyse embryos’ DNA to identify the embryos which are chromosomally normal.
What is DNA?
DNA stands for deoxyribonucleic acid and is the chemical that all forms of life on earth use as “instructions” about how to develop and function. It’s present in virtually every cell in your body and contains the genetic code which is unique to you.
World DNA Day celebrates the date James Watson and Francis Crick published their research on the structure of the DNA molecule, on 25 April 1953. Their work paved the way for countless scientific discoveries which led to major advances in the diagnosis and treatment of diseases.
The shape of DNA was shown to be a “double helix”, rather like a long, twisted ladder in which the rungs hold the genetic information. DNA molecules are very long and are coiled up very tightly into chromosomes.
How does DNA relate to IVF treatment?
Most cells in the body contain 46 chromosomes (23 pairs, one chromosome from each parent in each pair). Mature eggs and sperm each contain half that number – 23 single chromosomes – which come together during fertilisation to form an embryo with the 46 chromosomes necessary for normal development to a baby. If an embryo doesn’t have 46 chromosomes, or if the DNA within a chromosome is damaged, patients might find it more difficult to become pregnant or could be at higher risk of miscarriage. However, there are many things we can do to help identify any problems and create a treatment plan which will give you your best chance of having a healthy baby.
When a sperm fertilises an egg, the resulting embryo should have 23 pairs of chromosomes, one of each pair from the egg and the sperm. If an embryo doesn’t have the right number of chromosomes, it results in a failure to implant, miscarriage or (rarely) a child with a serious genetic condition.
How do I know if my embryo has the right number of chromosomes?
Embryos with the wrong number of chromosomes are known as aneuploid. Any patient can be at risk of having aneuploid embryos. In fact, most have a mix of aneuploid and normal.
The number of aneuploid embryos is known to increase as a woman gets older. Each month before ovulation, eggs go through a process of maturation, concluding with cell division (called meiosis). Older eggs are more prone to errors during this division process, which is why it’s more likely that older eggs will contain abnormal DNA. For women over 37, at least half of embryos are likely to be aneuploid, and the incidence increases to almost 80% by age 43.
Embryos can be tested to see if they are aneuploid or not. This test is called PGT-A (Pre-implantation Genetic Testing for Aneuploidy). PGT-A works by analysing the amount of genetic material within embryos, checking how many chromosomes are present. In order to do this, a small number of cells are carefully removed (biopsied) from the outer layer of a blastocyst-stage embryo, and these cells are then sent to a specialist genetics laboratory for analysis. We would recommend that only chromosomally normal embryos are considered for replacement back into the womb, however all patients who choose PGT-A will have free appointments with our specialist fertility and genetics counsellors to help them decide on the treatment that is best for them.
PGT-A could shorten the time from treatment to successful pregnancy as it prevents transfer of embryos that are aneuploid. Embryos with a normal number of chromosomes have lower miscarriage rates and higher live birth rates per embryo transfer.
We can even do PGT-A testing on embryos that are already frozen. If you have frozen embryos and wish to know if they have the potential to lead to successful treatment, they can be thawed, biopsied for PGT-A, and then re-frozen. 98% of embryos survive thaw at Care, and if a patient has embryos elsewhere, we can transport them to one of our clinics for testing.
Careunity test
Embryos that inherit a particular gene variant, known as the Annexin A5 gene M2 haplotype (also known at Care as C4M2), are at an increased risk of failing to implant or of miscarrying. As the priority at Care is to do everything possible to help our patients, the team have worked on a test that supports identifying one of the causes of miscarriage.
The Careunity screening test can identify the presence of the Annexin A5 gene. If the gene is present in either the sperm or the egg provider, then there is at least a 50% chance that it will be present in the embryo. The test is simple, requiring a swab taken from the inside of the mouth of both partners and results take approximately 3 weeks. If the Annexin A5 Variant is found from either partner, the patient having the embryo transfer will be prescribed a blood thinning medication from the stage of embryo transfer until at least 12 weeks of the pregnancy.
How can DNA damage affect fertility treatment?
Many factors can cause DNA damage within all cells, including eggs and sperm, but using screening tests such as sperm DNA damage screening and the sperm oxidative stress test can provide an assessment. DNA damage can be caused by factors including your lifestyle factors or age.
Sperm DNA damage screening
If you are struggling with recurrent miscarriage or implantation failure, unexplained or persistent infertility, low fertilisation rates or poor embryo quality in IVF cycles, we would recommend sperm DNA damage screening.
For this screening, you simply need to provide a semen sample. The sample is then frozen and transported to our laboratory, where it will be thawed and tested for DNA damage.
Sperm oxidative stress test
For up to 50% of couples who require help starting a family, male factors will be the cause of infertility issues. A general semen analysis is often labelled the ‘gold standard’ of assessing the quality of sperm, after analysis 25 - 40% of male infertility cases could remain ‘unexplained’.
Oxidative stress is a factor that can cause ‘unexplained infertility’, where high levels of oxidative stress have been linked to poor sperm function and cell DNA damage. Our bodies create antioxidants to minimise levels of oxidative stress, the ability to produce antioxidants is controlled by our genetic makeup but can also be influenced by lifestyle, such as a diet rich in fruit and vegetables. DNA damage is increased by factors such as smoking, alcohol, ageing and a poor-quality diet high in saturated fats and excess weight.
As high levels of oxidative stress have been linked to poor sperm function, our SOS (Sperm Oxidative Stress) test can identify if a patient has high levels of oxidative stress by assessing the balance of DNA damaging particles (known as free radicals) and antioxidants in a semen sample. If the main cause of DNA damage is identified as being oxidative stress, lifestyle changes and antioxidants can be introduced. This test can be done at any time during fertility treatment at Care, or at the same time as a normal semen analysis. Our SOS test is a quick way of identifying whether further testing is necessary.
If you are interested in PGT-A, Careunity, the SOS test or would like to learn more, get in touch with your Care clinic; our team will be happy to answer all of your questions.
