Inheriting the Uninheritable.

Story at a Glance

  • There are genetic causes of infertility that you can pass on through IVF.
  • It means that the next generation may be infertile as well.
  • Intra-Cytoplasmic Sperm Injection (ICSI) is a treatment for infertile men in which an individual sperm is selected and injected directly into an egg. Some studies suggest that IVF children born from ICSI may be at higher risk of medical problems, as they grow older, including male infertility.

 

Infertility affects 1 in 6 Australian couples. 40 percent of those problems will be due to sperm issues, 40 per cent will be because of female reproductive issues. And the rest get bundled up in a combination of both. In a nutshell, what that used to mean was that when it came to having kids, you were out of luck.

But with the miracle of science all of that changed. In 1980 Australia had their first IVF baby. We were on! Science had worked out how to fix it. Babies it seemed were there for the taking, or making.

However, with this ground breaking progress came what was previously unimaginable – being able to inherit the uninheritable.

Dr Andre van Steirteghem, who pioneered the IVF process, has noted that we may find ourselves facing a generation of children who have inherited their parent’s inability to conceive, in effect, growing a generation of offspring who might not be able produce their own offspring. At least not without a petri dish.

“There are genetic causes of infertility that you can pass on,” said Dr Van Steirteghem. “It means that the next generation may be infertile as well and this is something all clinics should mention to the patients – that if there is a genetic origin that this genetic origin of infertility may be transmitted to the next generation.”

But it’s not just infertility we’ve managed to inherit. With the invention of or Intra-Cytoplasmic Sperm Injection (ICSI), a treatment for infertile men in which an individual sperm is selected and injected directly into an egg, has come other issues. It’s used specifically for patients who failed IVF and specifically in the case where there are problems with a man’s sperm.  The concern has been that the sperm being used would normally be too unfit to fertilise an egg. The upshot with unfit sperm is you’re passing on increasing risks of genetic defects in the child.

As far back as the 1980’s there were calls for fertility clinics in Britain to cut down on its use. Dr Van Steirteghem, of the Brussels Free University Centre for Reproductive Medicine, who invented the procedure, said in Britain around 43 percent of fertility treatments use it. And in private clinics it’s around 77 percent.

“When you have a method like conventional IVF which is certainly less invasive than ICSI and that can help couples with female infertility where the sperm count is normal, I don’t see any reason why ICSI should be used,” he said.

In North America and Europe for instance – the figure is even higher, with ICSI being used in as many as 90 to 95 percent of IVF cycles. Yet some studies suggest that IVF children born from ICSI may be at higher risk of medical problems, as they grow older, including male infertility.

Lisa Jardine, former chair for the Human Fertilisation and Embryology Authority (HFEA), said that some IVF clinics use ICSI simply because the procedure is easier than IVF, rather than because it is in the best interests of patients.

“We believe it is being used far too widely because it is procedurally easy,” Professor Jardine said. “The scientists who advocate it already know that a boy born through ICSI is likely to have a low sperm count. So it is a little bit worrying that it is being rolled out so widely.”

Professor Carmen Sapienza, Fels Institute for Cancer Research and Molecular Biology, from the Lewis Katx School of Medicine at Temple University in Philadelphia has been researching the epigenetic differences of IVF babies compared to that of other children 1,2. Our cells regulate the turning on and off genes by a process called methylation. Methylation is where a methyl group is added to the DNA strand which in turn inhibits the gene from being expressed. This is what we call epigenetics, the turning on and off of genes.

This process of methylation begins at conception. His research has shown that being conceived in a lab and not in a uterus affects this process. The DNA of children born from IVF have less methylation than those conceived naturally. Which essentially means that they are at greater risk of diseases such as diabetes and obesity later in life because their genes are not being activated at the right time.

He notes, “Epidemiological studies suggest that children born through assisted reproduction are at substantially increased risk for several rare diseases associated with defects in epigenetic marking of the genome. We have demonstrated that children conceived in vitro have multiple DNA methylation and gene expression differences when compared with their in vivo-conceived counterparts.”

“These epigenetic differences have the potential to affect embryonic development and foetal growth, as well as influencing long-term patterns of gene expression associated with increased risk of many human diseases.”

These differences however are modest in size; the risks of birth defects were small, with 90 percent of children in the IVF group within the normal range of activity of genes.

“The health of children has to be considered the most important outcome of artificial reproductive technology treatment. It’s fair to say that overall these children do well [but] there are a few more problems with these children,” Dr Van Steirteghem said.

It’s an important area of research that needs to be continued into all areas of assisted reproduction. At this stage scientists are unsure as to whether infertility in offspring or the increase in their health problems is due to the process of IVF itself or if it’s an inherited problem passed on from an infertile parent. Either way, it’s a question that requires further examination. As we continue to forge ahead into the brave new world of creating humans, everyone deserves the best information available in which to make the most informed choices.

References

[1] A Molecular Perspective on Procedures and Outcomes with Assisted Reproductive Technologies. Mainigi MA, Sapienza C, Butts S, Coutifaris C. Cold Spring Harb Perspect Med. 2016 Apr 1;6(4):a023416. doi: 10.1101/cshperspect.a023416. Review. PMID: 26747835

[2]  DNA methylation differences between in vitro- and in vivo-conceived children are associated with ART procedures rather than infertility. Song S, Ghosh J, Mainigi M, Turan N, Weinerman R, Truongcao M, Coutifaris C, Sapienza C. Clin Epigenetics. 2015 Apr 8;7:41. doi: 10.1186/s13148-015-0071-7. eCollection 2015. PMID: 25901188

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