“Can you test our embryos and see if they are healthy?” This is a common question we get when we discuss the process of IVF treatment and the information the embryologists get from their microscopes during fertilization. This subject has attracted further interest with the advance of preimplantation genetic testing, a screening test for genetic conditions that is now available in many fertility centers, for conditions such as thalassemia and cystic fibrosis.

The advance of human genetics has made it possible to collect samples and check the entire DNA code from different populations and so determine which gene versions may be responsible for disease development

While embryologists can tell much about the microscopic images of embryos, the number of cells, their shape and structure, the way embryos divide and grow within the first few days of life, the genetic code of embryos remains unknown, unless an embryo biopsy is put in action, a very delicate procedure, where small numbers of cells from the outside of an embryo are removed and sent over to genetics for screening tests.

Although genetics have been documented to contribute to many diverse disease processes , it is only a minority of those conditions that are solely due to a certain genetic background. Where disease is the result of a single gene we deal with a “monogenic condition”, as in thalassemia and cystic fibrosis for example, where preimplantation genetic diagnosis can successfully test an embryo through IVF for the faulty gene and allow only healthy embryos to be transferred.

However, the commonest health problems that present in our life span result from the interaction of our genetic background with the environment we live and the lifestyle we follow. Conditions such as diabetes, heart disease, cancer, Alzheimer disease, are all common health problems that account for the majority of health problems encountered in adult life. There is no one single gene that can predict the development of these conditions, except in a minority of cases. Instead, many different versions of genes have been identified that appear more often in such cases, shifting our interest from a single to a number of gene targets. Disease conditions such as these are called “polygenic”, as it is in the combination of a number of gene versions that we focus trying to get an estimate of how possible it is for the disease to happen.

The advance of human genetics has made it possible to collect samples and check the entire DNA code from different populations and so determine which gene versions may be responsible for disease development. By comparing genetic backgrounds in healthy populations with populations where the disease if present geneticists have provided a list of gene candidates that determines the possibility of developing a specific condition. “Polygenic risk scores” are now attracting increasing attention, as a means to predict, prevent and manage early the possibility of health problems in future.

However, the application of genetics in predicting disease of such origin, where multiple genes are involved, is not an easy task, especially when the discussion turns to IVF treatment and pre-implantation genetic testing. Although the experience from successfully testing for monogenic conditions (thalassemia and cystic fibrosis) is long and well documented, the same cannot be held for polygenic conditions. Not only limitations of laboratory testing at present, but the nature of such health conditions mostly, makes it a challenge to use at everyday clinical practice. The reason being that even if we get genetic information about the possibility of developing diabetes, for example, we still lack the information about the role of environment and lifestyle an individual may adopt in future. Moreover, as studies have collected a vast amount of genetic information of populations at a certain point of time, we should question whether results of useful for health professionals in a different time and location in future, where not only the environment will have changed but along with it our everyday habits.

Concluding, checking IVF embryos for health problems is not only feasible but highly successful for monogenic conditions, where genetics are straight forward, and this is the core of preimplantation genetic testing nowadays in IVF labs. As human genetics advance rapidly we can also screen for polygenic conditions and stratify risk for disease development in future, however, the value of such an approach is still under investigation, as crucial questions remain to be answered: how accurate is the information we gather at such an early point of life, while we have a limited idea of the complex interaction with the environment.

©2021, Nicholas Christoforidis, Fertility Matters
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