Epigenetics and its relation to IVF

In the field of genetics, the topic of epigenetics examines the changes in gene expression caused by mechanisms above and beyond the changes found in the DNA structure itself. Some of these changes are heritable. In other words, modifications to the genome in form and function occur without the DNA sequence having been altered. Instead, the modification of histones and methylation of the DNA occur, resulting in changes in gene expression, phenotypic form and function.

One of the fundamental principles of nuclear transfer cloning is that the cell responds to certain conditions provided by the environment in which it is maintained. Changing these conditions effectively reprograms the cell and may result in vastly different functionality; the genome of that cell remains identical to the genome of the cell from which it was derived.

The epigenetic environment is one that is highly regulated and imparts strict regulation on the development of an embryo. Thus, histone modification and DNA methylation can prove lethal to developing fetuses and may be responsible for many IVF failures. The human genome itself has a substantial fraction of segments that are vulnerable to changes in the environmental conditions, resulting in unwanted and often devastating gene expression.

Couples seeking to bear children while also facing the obstacles associated with infertility turn toward assistive reproductive technology as their best option for having a child. However, there have been questions and concerns about the long-term safety of manipulating sperm, ova, and embryos. Short-term outcomes have been studied, and it is known that multiple births and low birth weight are associated with assisted reproductive technology. Philippines-based and ART centers worldwide face the same pressures—not only for the end result to be a live birth carried to term, but one that is normal and free of defects.

With regards to in-vitro fertilization, studies have suggested that IVF carries a small but increased incidence of diseases such as Angelman syndrome, retinoblastoma, and Beckwith Wiedemann syndrome. This does not imply that IVF causes these disorders to occur, but a correlation may be present, and further study is needed to understand what risk, if any, exists for such imprinting aberrations to occur.

Other studies have shown that developmental differences have not been established when comparing children conceived naturally against those conceived via intracytoplasmic sperm injection (ICSI) and IVF. Another study identified and reported a case of Prader-Willi syndrome. Since low birth weight and Prader-Willi syndrome are partially controlled by epigenetics, it is plausible to rationalize the association between birth defects and assisted reproductive therapies. Moreover, another question has arisen: which diseases are those who were conceived via ART susceptible to when they become adults?

Fortunately, the outcomes for detrimental health effects of assisted reproductive technologies are small, and the vast majority of cases result in healthy, singleton live births. However, professionals in ART should disclose the risks of such occurrences to prospective parents so they can make an informed decision.