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Assisted Reproductive Technologies (ART) and the long-term health of offspring

Research project

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.

1. 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, the majority of measures were similar for both groups and no specific concerns were raised. These findings were published in 2014 and received wide media attention.
View publication Comparing indicators of health and development of singleton young adults conceived with and without assisted reproductive technology.

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.

This project was funded by the National Health and Medical Research Council (NHMRC project grant APP1099641). It was also supported by the Monash IVF Research and Education Fund, Melbourne IVF and MCRI in conjunction with the RCH 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 also 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. This was published in 2019 also.
View publication American Heart Association ideal cardiovascular health score and subclinical atherosclerosis in 22-35-year-old adults conceived with and without assisted reproductive technologies.

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. This was published in 2019 again to much media attention.
View publication Assisted reproductive technologies are associated with limited epigenetic variation at birth that largely resolves by adulthood.

2. 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.

3. 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 either 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 more than 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.

In this study parents of young men born between 1994 and 2000 were asked to participate by completing an online questionnaire. With parental consent, we also invited the adult sons to participate. Their participation was completing a questionnaire and undertake a clinical review. This included a physical examination, blood test, semen test and saliva sample. Each of these tests were optional. 

Funding

This project has been funded by a Partnership Grant through the National Health and Medical Research Council (NHMRC APP1140706), 2018-2020. Partners are the Hudson Institute of Medical Research, in conjunction with Victorian Assisted Reproductive Treatment Authority (VARTA), Monash IVF Group, Melbourne IVF, Fertility Society of Australia (FSA) and ACCESS. It has also previously been supported by the Monash IVF Research and Education Fund.

Results

Results of this study form the basis of Dr Sarah Catford’s PhD and will be available soon. Publications so far are found here: