The PRONATAL Genetic Laboratory primarily tests infertile couples, gamete and embryo donors. Another part of our work is the examination of patients with oncological diseases, where we look for a possible genetic cause of their condition; the examination result can then determine their treatment.
How can genetics help in the treatment of infertile couples?
Infertile couples often do not decide to visit a specialised assisted reproduction centre for a very long time, even if they have not been able to conceive for an extended period. Using one example, I will show that a comprehensive approach to treatment and the cooperation of specialist doctors is fundamental. The following life story seems like a fairy tale to me. There was once a married couple who loved each other and wanted to have children. But it didn't work out. After two years of trying, they contacted an assisted reproduction centre for help. First, three cycles with intrauterine insemination, then 6 IVF cycles with a total of 17 embryos transferred, all without success. The despair and hopelessness of the patient and her husband I cannot even imagine. When this couple came to our centre, they were advised to consult a clinical geneticist. A karyotype examination of both partners revealed where the problem was. The lady was a carrier of a balanced translocation, which was most likely the cause of her repeated reproductive failures. In the next cycle, preimplantation genetic testing was performed on the 9 embryos retrieved, 2 embryos were recommended for transfer, and the patient finally became pregnant and gave birth to twins after six years of difficult treatment. This illustrates the importance of a correct diagnosis. If - after two years of trying to conceive - the couple had been immediately recommended for genetic counselling, the genetic cause of their infertility would have been discovered at the start of treatment, and they could have saved themselves a gruelling six-year marathon of hormonal stimulation, repeated disappointments and unnecessary financial costs.
There was one more couple that really stuck in my mind. A gentleman called our genetics department to learn more about embryo testing because his wife is a balanced translocation carrier, and they were recommended PGT. They had already had one unsuccessful cycle at another centre. When he and his wife arrived for the appointment, you could see at first glance how unhappy, sad, and speechless his wife was...while the gentleman was active and full of energy and faith that everything would work out. The lady felt guilty; she thought that she was the reason why they still did not have children, and her psychological state was grim. When we explained to them how the whole process works, that we routinely examine several hundred embryos a year, and that it is essential for them to have only enough embryos from which to select the genetically suitable ones right in front of our eyes, the lady changed as she began to trust us. In the first IVF/PGT cycle at our centre, out of the 8 embryos examined, we recommended 3 suitable embryos for transfer. We transferred 2 embryos and hoped that the pregnancy would be successful this time. After 9 months, the couple called again, this time from the maternity hospital where they just had their twins born, a boy and a girl. I must admit that we all cried at that phone call, me in the lab and the whole family and the grandparents in the distant maternity ward; that's how intensely emotional and thrilled everyone was. After a year, they sent us beautiful photos in which the mother was literally shining as if she had been replaced. There was no trace of the sad and unhappy patient; now, she thoroughly enjoyed her motherhood and family happiness. I felt like a miracle had happened.
In many families, hereditary diseases caused by mutations in various specific genes are passed down from generation to generation. Can you help here too? It's not like these are infertile couples.
This is not the case for infertile couples, but our clinic can also help here. The method is called preimplantation genetic testing for monogenic diseases. The patient undergoes hormonal stimulation to get more eggs and embryos. Preimplantation genetic testing is performed on trophectoderm cells taken from developing embryos on day 5 after fertilisation, the cells taken are not part of the developing embryo, and thus, their removal does not affect the further growth of the embryo. Only "healthy" embryos are recommended for transfer to the uterus after the examination and will be transferred to the woman in one of her subsequent cycles. By selecting 'healthy' embryos, we can break the chain of hereditary disease that often runs for generations in families, with the threat of giving birth to a sick child hanging over everyone. Prenatal cellular testing of a spontaneously conceived foetus is, of course, also a way to prevent the birth of a sick child. Still, if the foetus is diagnosed with a disease, this route is associated with the trauma of terminating the pregnancy. PGT is ethical because it does not expose couples to this trauma.
In addition, we offer couples planning a pregnancy, and not only infertile couples, the possibility to find out if they are carriers of common recessively inherited diseases. Such diseases include cystic fibrosis, non-syndromic deafness, spinal muscular atrophy, phenylketonuria, etc. Carriers have no symptoms of the condition, but if two carriers of the same disease come together, they find a 25% risk of having a sick child. Couples who are found to be at reproductive risk can be offered preimplantation embryo testing for monogenic disease. Taking advantage of the opportunities that reproductive genetics offers today is, in my opinion, a sound, sensible and good investment in the health of our children. And it makes much sense in our work.
RNDr. Marcela Kosařová, Ph.D. - PRONATAL Genetic Laboratory
