Assisted Reproductive Technologies (ART) and the long-term health of offspring
- Project status: Active
Research area: Genomic Medicine > Reproductive Epidemiology
Assisted Reproductive Technologies (ART) were pioneered in Victoria and therefore people conceived by IVF are now up to 40 years of age.
The aim of our research into young adults conceived by ART has been to investigate their long-term health outcomes.
The aim of our research into young adults conceived by ART has been to investigate their long-term health outcomes.
Overview
Assisted Reproductive Technologies (ART) were pioneered in Victoria and therefore people conceived by IVF are now up to 40 years of age.
There is a widely held belief that common adult onset disorders (particularly cardiovascular and respiratory diseases) begin in early life, possibly even before birth. Children born following the use of ART might therefore be in a specific risk category because of the techniques used to enable successful pregnancies. The aim of our research into young adults conceived by ART has been to investigate their long-term health outcomes.
By undertaking surveys, various clinical assessments and epigenetic analyses, we have addressed a shortfall in knowledge.
Research
Clinical review of the Health of 22-33-year-olds conceived with and without ART (CHART study)
Stage one of the study was called “Comparison of health and development of young adults aged 18 years and older, conceived with and without ART” and was conducted in 2011-2013, funded by NHMRC. We interviewed by phone 547 young singleton adults who were born from assisted conception, along with 549 young adults who were born without assisted conception. Overall, most measures were similar for both groups and no specific concerns were raised. These findings were published in 2014 and received wide media attention.
In 2016, we began the CHART follow-up study of these same adults, now aged 22 years and older (average of 27 years), inviting them in for clinical tests to check their heart and lung health.
The National Health and Medical Research Council (NHMRC project grant APP1099641) funded this project. The Monash IVF Research and Education Fund, Melbourne IVF and MCRI also supported it with the Royal Children's Hospital Foundation.
Results from CHART
After a rigorous tracing and follow-up process, we recruited 193 ART-conceived individuals and 86 controls. Results were published in Fertility and Sterility in 2019 with a media reach of 3.1 million. It was the largest study to date globally and found no evidence of increased vascular or cardiometabolic risk or growth or respiratory problems in the ART-conceived participants compared to the non-ART controls.
The data were analysed for risk factors that might predispose them to later onset cardiovascular problems using the American Heart Association ideal cardiovascular health score based on 7 factors: ideal BMI, blood pressure, total cholesterol, glucose, diet and physical activity, non-smoking. The associations between these risk factors and markers of subclinical atherosclerosis in ART and non-ART groups were similar in magnitude.
Finally, as the participants had provided blood samples and given permission for us to access their newborn blood spots, we were able to analyse their epigenetic profiles, comparing birth and adult samples. This exciting research identified specific ART-associated epigenetic variation, suggesting that infertility per se, or aspects of the technology such as ovarian stimulation, may affect the early embryo epigenome in a manner that is measurable postnatally. Importantly, ART-associated epigenetic variation at birth largely resolves by adulthood with no direct evidence that it impacts on development and health.
The Fertility And WellbeiNg (FAWN) study
Most recently, using funding from the McBain Family Trust, in 2020 we invited approximately 800 eligible adults from the original study to complete an online survey, focusing on their reproductive health in particular, as they were on average 31 years old . As well as asking about their fertility and childbearing, this survey asked questions about general physical health, diet and lifestyle habits, relationships and wellbeing. Approximately 310 ART-conceived and 155 non-ART conceived participants completed the survey and their responses are being analysed in 2021.
Health and fertility of young Men conceived using ICSI (HIM Study)
This is another project following up outcomes of people conceived by ART, this time focused on young men conceived by intracytoplasmic sperm injection (ICSI). The study aims to learn more about their health, development, well-being, and fertility. The fathers had ICSI because of a problem with sperm production or a blockage preventing the passage of sperm. Other studies have assessed the health and development of ICSI-conceived children, but only one study so far worldwide has evaluated ICSI-conceived young adults aged over 18 years.
It is extremely important to evaluate the health and fertility of young men conceived using ICSI because it is being used more and more frequently. More knowledge in this area will help us better inform couples who are struggling with infertility and assist fertility specialists worldwide.
During this study, parents of young men born between 1994 and 2000 were asked to take part by completing an online questionnaire. With parental consent, we also invited the adult sons to take part. Their participation was completing a questionnaire and undertake a clinical review. This included a physical examination, blood test, semen test, and a saliva sample. Each of these tests was optional.
Publications
- Long-term follow-up of intra-cytoplasmic sperm injection-conceived offspring compared with in vitro fertilization-conceived offspring: a systematic review of health outcomes beyond the neonatal period
- Long-term follow-up of ICSI-conceived offspring compared with spontaneously conceived offspring: a systematic review of health outcomes beyond the neonatal period
- Health and fertility of ICSI-conceived young men: study protocol
Contact us
Assisted Reproductive Technologies (ART)
Murdoch Children's Research Institute
The Royal Children's Hospital
50 Flemington Road
Parkville VIC 3052
Australia