Do IVF Children Have More Serious Infections?
A few months ago, a study was published in Fertility and Sterility that looked at whether or not there is an association between how a baby was conceived and the impact this mode of conception has on getting serious infections. It was conducted at the largest birth center in Israel, which is a country where the national law mandates that all citizens who need fertility treatments receive access to them.
This particular study was retrospective, which means that it is looking backwards at events that have already happened. It looked back in time at the medical records of infants born at this Israeli birth center between 1991 - 2014. The study excluded infants who were born with deformities or who were born as multiples like twins or triplets because they are generally considered higher risk; all in all, the study followed 242,187 infants for an average of ten years. (This was one of the main selling points of this study to me, because this is a lot of data from which to derive conclusions). Because this birth center has a special fertility unit, they were able to note that 2,603 infants had been conceived from in-vitro fertilization (aka IVF) and that 1,721 infants had been conceived with the help of medications that boost ovulation (aka ovulation inducers). The average time that these infants and children were followed was ten years.
All of these infants were followed until one of three events happened:
1) an infection brought them to the hospital
2) they died from something unrelated to an infection
3) they turned 18 (no longer considered children.
During this time, roughly 10% were hospitalized with one or more infections.
After accounting for and adjusting for the differences between groups, like the IVF group having older mothers in general, the study found that children conceived from IVF had the highest rates of infections needing hospitalization, followed by children conceived using ovulation inducers.
The actual numbers behind their results are a bit tricky to understand at first. Here’s how the results were described in the study… “the hospitalizations rates per 1,000 person years of follow-up were 16.34 in the IVF group, 11.61 in the Ovulation Inducers group, and 10.19 in the naturally conceived group.”
This means, if we watched 1000 children from each group for one year and looked for rates of hospitalization for serious infection, we would expect, on average:
16.3 children from the IVF group
11.6 children from the Ovulation Inducers group
10.2 children from the Naturally Conceived group
Comparing the IVF group to the naturally conceived, that is just six more children in one thousand who were hospitalized for infection; if you break the fractions down even further, it is not even 1 child in 100 who would additionally be hospitalized for infection if born from IVF vs. natural conception.
The study provided a table that disclosed the frequency of infections by diagnosis, and the only area with a statistically significant difference for increased infections in the IVF and Ovulation Inducers groups was in Upper Respiratory Infections. What this statistical significance means is that the differences found between these groups in Upper Respiratory Infections were NOT due to chance. What this also means is that they did NOT detect differences based on mode of conception for any of the other types of infections, which included ear infections, pneumonia, and stomach infections.
So, while the statistical method used in this study indicated that yes, there is a difference between children born from IVF compared to children naturally conceived, that doesn’t automatically mean that the difference is large or important enough to impact medical practices.
An outcome that I wish the study had provided were deaths - the study stopped following children if this happened, but did it happen? How often and to which children? Also, were there differences in the recovery time from the infections? This information is likely available in the medical records, so a follow-up on this would be useful.
Another study that would be useful is one that provides information about children born more recently from IVF or ovulation induction, as those children would be more closely comparable to the children that you or I will hopefully conceive once this pandemic is over. When looking at heart studies, which I will likely cover in a later episode, they found that IVF children born in the 90s had higher blood pressure compared to the naturally conceived, but this blood pressure difference was not detectable in children born with reproductive help from the 2000s. So, like the blood pressure study where the difference went away in the same timeline as the serious evolution of fertility techniques, I’m curious if the small difference found in the Israeli infection study winds up being even smaller for babies conceived with our current reproductive technology.
Overall, this was a valuable study. It looked at a lot of data which increases the ability to draw useful conclusions. With this large amount of data, there was just one category that found a small difference in serious infections; this really was an encouraging study for women who want to use IVF or ovulation inducers to become mothers.
Resources
Primary image used by permission of Oxford University Press. Berntsen S, Söderström-Anttila V, Wennerholm UB, Laivuori H, Loft A, Oldereid NB, Romundstad LB, Bergh C, Pinborg A. The health of children conceived by ART: ‘the chicken or the egg?’, Human Reproduction Update, Volume 25, Issue 2, March-April 2019, Pages 137–158, https://doi.org/10.1093/humupd/dmz001
Alexander LK, et al. Calculating Person-Time. https://sph.unc.edu/files/2015/07/nciph_ERIC4.pdf
Guo XY, et al. Cardiovascular and metabolic profiles of offspring conceived by assisted reproductive technologies: a systematic review and meta-analysis. Fertil Steril. 2017 Mar;107(3):622-631.e5. https://www.ncbi.nlm.nih.gov/pubmed/28104241
Hernan, MA. The Hazard of Hazard Ratios. Epidemiology. 2010 Jan; 21(1): 13–15. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653612/
Wainstock T, et al. Fertility treatments and offspring pediatric infectious morbidities: results of a population-based cohort with a median follow-up of 10 years. Fertil Steril. 2019 Dec;112(6):1129-1135. https://www.ncbi.nlm.nih.gov/pubmed/31843089
