The whole mainstream narrative around C-sections based on poorly controlled observational studies reminds me strongly of the debate over whether IVF is bad for children.
We know the IVF patient population has unusually high rates of health issues and that those issues are heritable, yet most analyses do not properly control for those differences when assessing whether IVF itself causes harm.
There’s basically three plausible ways in which IVF could theoretically impact the health of future children:
The process of culturing embyors could cause more de-novo point mutations
Embryo culturing could cause higher rates of aneuploidy
Embryo culturing could somehow cause developmental issues
As far as de-novo point mutations go, well-designed studies such as Smits et al. show no statistically significant difference in point mutation rates.
Aneuploidy can be screened quite well by PGT-A, which is already a routine part of over 50% of IVF cycles.
So that just leaves the last one, where it’s pretty difficult to separate the effects of IVF itself from exogenous factors like the health and infertility status of those who choose to go through it. My sense from reading the literature is that the effects, if they exist, are very small.
Yet I still see many articles like this one claiming that IVF itself causes worse health outcomes, essentially relying on nothing more than the observed correlation between IVF use and health issues.
It’s maddening how statistically illiterate many mainstream scientists at well-known institutions are. If you google “does IVF cause worse health outcomes” you’ll find three articles about cancer risk or “late life health problems”. What is the proposed mechanism here? Cancer is caused by very specific mutation pathways that lead to uncontrolled cell growth. IVF babies have no increased risk of point mutations, and aneuploidy doesn’t cause cancer.
This is all to say that I really appreciate posts like this one that actually tries to control for exogenous factors. It’s surprisingly rare to see people take this approach.
This article claims “different embryo culture media give rise to different birthweights and growth patterns in children” and “children born after ART have altered epigenetic profiles”.
I’m not an expert but I read it and found it quite plausible that there are ways that IVF can cause worse health outcomes. Would love to read a thorough critique of it!
Most of the differences listed in this analysis are basically retrospective cohort studies comparing outcomes of parents who sought IVF with those of parents who didn’t. I think these are likely to result in spurious hypothesis about negative effects of IVF. We know that parents who seek IVF are disproportionately unhealthy, and as such are likely to pass on their conditions to their children.
But I’d make on exception to this generality, which is the differences observed when using different culture media. In particular, the study from Kleijkers et al, which was a double-blind RCT of 836 couples. You almost never get a randomized study that large in IVF.
It found a difference in birth weight of 158 grams between children born using two different culture media. That’s a difference of about 4-6%.
That’s a relatively small effect. For comparison, women with preeclampsia who give birth early tend to have babies with birth weights about 350g below that of babies born to mothers without the condition (when matching for gestational age).
So while the effect is not very large, I believe it.
Super useful, I would love to read more of your IVF thoughts if they’re posted somewhere! I think your views imply that these new sperm obstacle courses, based on fears of a worse sperm-selection process in IVF, have zero effect on people’s eventual outcomes (conditional on viability)? But curious what you think. Example: “The SPARTAN system uses a series of obstacles on a microchip, requiring sperm to swim around pillar-shaped objects and through the device. As a result, this device promotes the collection of the highest quality sperm.”
The whole mainstream narrative around C-sections based on poorly controlled observational studies reminds me strongly of the debate over whether IVF is bad for children.
We know the IVF patient population has unusually high rates of health issues and that those issues are heritable, yet most analyses do not properly control for those differences when assessing whether IVF itself causes harm.
There’s basically three plausible ways in which IVF could theoretically impact the health of future children:
The process of culturing embyors could cause more de-novo point mutations
Embryo culturing could cause higher rates of aneuploidy
Embryo culturing could somehow cause developmental issues
As far as de-novo point mutations go, well-designed studies such as Smits et al. show no statistically significant difference in point mutation rates.
Aneuploidy can be screened quite well by PGT-A, which is already a routine part of over 50% of IVF cycles.
So that just leaves the last one, where it’s pretty difficult to separate the effects of IVF itself from exogenous factors like the health and infertility status of those who choose to go through it. My sense from reading the literature is that the effects, if they exist, are very small.
Yet I still see many articles like this one claiming that IVF itself causes worse health outcomes, essentially relying on nothing more than the observed correlation between IVF use and health issues.
It’s maddening how statistically illiterate many mainstream scientists at well-known institutions are. If you google “does IVF cause worse health outcomes” you’ll find three articles about cancer risk or “late life health problems”. What is the proposed mechanism here? Cancer is caused by very specific mutation pathways that lead to uncontrolled cell growth. IVF babies have no increased risk of point mutations, and aneuploidy doesn’t cause cancer.
This is all to say that I really appreciate posts like this one that actually tries to control for exogenous factors. It’s surprisingly rare to see people take this approach.
This article claims “different embryo culture media give rise to different birthweights and growth patterns in children” and “children born after ART have altered epigenetic profiles”.
I’m not an expert but I read it and found it quite plausible that there are ways that IVF can cause worse health outcomes. Would love to read a thorough critique of it!
Interesting study, thanks for the link.
Most of the differences listed in this analysis are basically retrospective cohort studies comparing outcomes of parents who sought IVF with those of parents who didn’t. I think these are likely to result in spurious hypothesis about negative effects of IVF. We know that parents who seek IVF are disproportionately unhealthy, and as such are likely to pass on their conditions to their children.
But I’d make on exception to this generality, which is the differences observed when using different culture media. In particular, the study from Kleijkers et al, which was a double-blind RCT of 836 couples. You almost never get a randomized study that large in IVF.
It found a difference in birth weight of 158 grams between children born using two different culture media. That’s a difference of about 4-6%.
That’s a relatively small effect. For comparison, women with preeclampsia who give birth early tend to have babies with birth weights about 350g below that of babies born to mothers without the condition (when matching for gestational age).
So while the effect is not very large, I believe it.
If I wanted to hypothesize a possible mechanism, an increased number of transposons might be a possible mechanism. There’s “transcriptional reactivation of retrotransposons in the early mammalian embryo” and it’s plausible that the deactivation happens later in a cultured embryo.
Super useful, I would love to read more of your IVF thoughts if they’re posted somewhere! I think your views imply that these new sperm obstacle courses, based on fears of a worse sperm-selection process in IVF, have zero effect on people’s eventual outcomes (conditional on viability)? But curious what you think. Example: “The SPARTAN system uses a series of obstacles on a microchip, requiring sperm to swim around pillar-shaped objects and through the device. As a result, this device promotes the collection of the highest quality sperm.”
I’m writing a post on how to have polygenically screened children. I’ll ping you when it goes up.
Well it has been 7 long months since I wrote this comment and you may have lost interest, but the post is finally up