REPRODUCTIVE TECHNOLOGIES AND BIRTH DEFECTS

By Dr Katrina Rowan

A very important study out of the University of Adelaide has just been published in the New England Journal of Medicine, one of medicine’s most reputable journals: http://www.nejm.org/doi/full/10.1056/NEJMoa1008095#t=article.  The study methodology was excellent, using large databases to ensure accuracy of their data, and adjusting for many factors that can interfere with the results of these types of studies.   

We have known for a while that IVF and particularly ICSI is associated with an increased risk of birth defects, but we are unsure of why this is.  Several previous studies have shown this risk to be 30-40% greater, or an absolute risk of 3-4% birth defects in IVF pregnancies compared to 2-3% in natural pregnancies.  This study looked to confirm these risks and try to sort out what parts of reproductive technologies gave the greatest risk. 

Whilst the overall percentages of birth defects with IVF in this study seemed concerningly high (8.3% vs 5.8% for non-IVF pregnancies) there were several possible explanations for this number.    Firstly, this was the unadjusted risk, and when adjusted for important factors such as maternal age the risk was lower.  One big difference to other studies in that cerebral palsy was counted as a birth defect, thus giving the higher absolute numbers of birth defects seen.  For their overall results, the authors didn't separate twin pregnancies from singleton pregnancies.  Twin pregnancies are known to be at higher risk of all birth defects, especially cerebral palsy.    They also didn't separate single embryo transfer from double embryo transfer.  Even if it results in a singleton birth, previous research has shown double embryo transfer to be associated with a higher risk of birth abnormalities than single embryo transfer. 

This study has also shown that frozen embryos were a lower risk of birth abnormalities than fresh embryos.  This was certainly very interesting and provides reassurance about the safety of single embryo transfer with freezing excess good quality embryos.   It is also reassuring for patients who need to freeze all of their embryos, for example if they have ovarian hyperstimulation syndrome.  This study does confirm that babies conceived after ICSI (injection of the sperm) than IVF.

Another important new finding in this study was that subfertile people who conceive naturally were also more at risk of birth defects, and this rate was no different to subfertile people who conceived with IVF.   This suggests that it is more likely parental factors (for example an unidentifiable genetic problem) that is the reason for an increase in birth abnormalities, rather than the IVF technology.  This may well be why ICSI pregnancies are associated with higher birth defects, as ICSI is normally performed when there is a very abnormal semen analysis, and there could be a genetic problem causing this. 

So what does it all mean for infertile couples considering or having IVF treatment???

Firstly, IVF should only be used when the benefits outweigh the potential risks.  The same principle applies to ICSI.

If you need IVF or ICSI, sticking to single embryo transfer with freezing of extra embryos is likely to keep this risks at an absolute minimum. 

Thought should be given to freezing all embryos especially if there is a medical reason to (such as ovarian hyperstimulation). 

IVF pregnancies should be treated as high risk, and the best possible obstetric care should be applied.

 

In the end, IVF is the only or most likely way to pregnancy for many people, and a small absolute increase in the risk these, many surgically correctable, abnormalities is worth the risk for many suffering with involuntary infertility.

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