What is epigenetics? Epigenetics is a cellular marking system that controls whether genes are active or inactive. This marking system goes through changes during the creation of sperm, egg, and in the early embryo following fertilisation. These changes are natural and essential for development.
How is epigenetics relevant to reproductive medicine and assisted reproduction? Assisted reproduction involves the creation of embryos by in vitro fertilisation (IVF) and may also involve other specialised techniques involving the sperm and egg. The natural phases of epigenetic changes that occur in the egg, sperm and embryo(s) take place at the same time that these are handled in the assisted reproduction laboratory.
Can assisted reproduction lead to epigenetic changes? It is very difficult to be certain whether assisted reproduction and any assisted reproductive technologies (ARTs) can lead to significant epigenetic changes. It is also unknown whether any epigenetic changes will lead to a significant difference in growth and development of the embryo. This is due to the difficulties in studying these intricate processes in the sperm, egg and embryo. Therefore further research is needed before we can answer this question.
What does the latest research show? Research in animal models suggests that assisted reproduction may affect embryo growth and development, but the evidence for humans is less clear. It is not always appropriate to make conclusions based on animal studies because there are differences in epigenetic processes between mammals. Lifestyle choices, diet, the patient’s genetic make-up and age are also very important in shaping the human epigenome. There are also conflicting findings on whether the different types of liquid used in the dishes where embryos develop can affect child birthweight.
How will this paper help health professionals/IVF specialists? The paper will improve clinicians’ understanding of how epigenetics is relevant to their field of expertise. Recommendations are made for accurate record keeping of assisted reproduction cycles, monitoring of health in babies born following assisted reproduction, and for openness within the fertility industry on products used in the assisted reproduction process.
How will this paper help patients undergoing assisted reproduction? This paper does not make any recommendations for patients. The evidence is very limited and more research is needed to make definitive conclusions about the impact of assisted reproduction on epigenetics. It is important to note that ARTs are safe and highly regulated in the UK. If patients have any questions or concerns, they should speak to their health professional. There is information available on the HFEA website.
What should future research focus on? More research is required to understand the natural epigenetic processes in human sperm, eggs and embryos and to define whether ARTs and/or the underlying causes of infertility can affect these processes. Recent advances in molecular biology that allow sensitive epigenetic analysis of the entire genome will help improve our understanding. Further research is also required to determine any possible long-term health effects of assisted reproduction, including cardiovascular and metabolic disorders.
This Scientific Impact Paper was developed prior to the emergence of the COVID-19 coronavirus.
This is the first edition of this paper. Please note that the Scientific Advisory Committee regularly assesses the need to update. Further information on this review is available on request.
Developer declaration of interests
Dr J Huntriss, Discovery and Translational Science Department (DTSD), Leeds Institute of Cardiovascular and Metabolic Medicine: None declared.
Professor AH Balen FRCOG, Leeds: Professor Balen is a Member of the World Health Organization (WHO) International Committee Monitoring Assisted Reproductive Technologies (ICMART) and Committee Member of the International Steering Committee of the WHO Global Infertility Guidelines Group, as well as recent past Chair of the British Fertility Society. He is also a Member of the Medical Advisory Board of Fertility Network UK, as a medical advisor on female infertility and Patron of ACeBabes, the national society for parents and children born by assisted conception.
Professor Balen has been a consultant on ad hoc advisory boards for Astra Zeneca, Clear Blue, Ferring Pharmaceuticals, Glaxo Smith Kline, Gideon Richter, Merck Serono, Merck Sharp & Dohme, OvaScience (former member of ethics committee), Pharmasure and Uteron Pharma, and past Chair of the Clinical Board at IVI UK.
Professor Balen is Director of Genesis Healthcare LLP (Private IVF Unit within Leeds Fertility, Leeds Teaching Hospitals) and Director of Balance Reproductive Health Ltd and Partner in Balance Health Ltd, Balance Mind Ltd, Balance Fertility Ltd.
Professor DR Brison, Department of Reproductive Medicine, Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre: Professor Brison is an Examiner in Embryology for the Royal College of Pathologists, Scientific Advisory Committee Member for the Association of Clinical Embryologists, Scientific Advisor to the Human Fertilisation and Embryology Authority, and Scientific Advisor on IVF to the Medicines and Healthcare Regulatory Agency. He is an Honorary Professor at the University of Manchester and at Manchester Metropolitan University.
Professor HM Picton: None declared.