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Welcome to The Nonlinear Library, where we use Text-to-Speech software to convert the best writing from the Rationalist and EA communities into audio. This is: Reply to a fertility doctor concerning polygenic embryo screening, published by GeneSmith on May 29, 2023 on LessWrong.
New LessWrong user grll_nrg, a fertility doctor, left a comment on my post about how to have polygenically screened children that brought up many of the common objections raised to polygenic embryo screening. I've heard these concerns brought up many times at conferences and in talks by professionals in the fertility industry. I thought other people might be interested in the discussion, so I decide to make a stand-alone post.
Here's grll_nrg's original comment:
Great post. Thank you. Fertility doctor here and a supporter of ART (assisted reproductive technologies) in general. A few thoughts (although you touched on a few of these below, worth emphasizing in my opinion):
PGT-P has not been validated yet, which may take decades to do, if ever.
The science in terms of GWAS isn't quite there yet IMHO - we don't know all the genes that are important for most traits and we may be inadvertently selecting against some desirable traits, for example.
Comparing clinic success rates using CDC data is imperfect because of different patient characteristics, patient selection, and reporting bias.
IVF pregnancies carry a significantly higher complication rate (hypertensive disorders, preterm birth, placental abnormalities, etc.) compared to spontaneous pregnancies - unclear if this is due to IVF or underlying infertility diagnosis.
The risk-benefit calculus of PGT-P is going to be different for a couple who already needs to do IVF anyway to have a baby (low additional risk/cost) compared to a couple doing IVF just so that they can do PGT-P (higher additional risk/cost).
IVF is notoriously inefficient at present. Depending on female partner age, each cycle may yield only very few embryos making the benefit and utility of PGT-P limited. It may not be practical, safe, or financially feasible to do multiple cycles of IVF to increase the cohort of transferable embryos.
IVF is expensive and often not covered by insurance which creates access disparities. PGT-P would exacerbate these disparities in access. This is not unique to IVF I realize.
Slippery-slope eugenics and discrimination are real ethical concerns that would need to be mitigated.
In-vitro gametogenesis (IVG) would be a game-changer. The utility of PGT-P would be greatly enhanced if suddenly you had thousands of eggs and hundreds of embryos to select from.
Thanks for the reply. I'm glad professionals from the ART field are reading this.
PGT-P has not been validated yet, which may take decades to do, if ever.
I think the ART field should probably reconsider what it considers acceptable evidence of "validation". In my mind, the question of "Has PGT-P been validated" should hinge on whether or not we can be confident that embryos selected via polygenic scores will display different trait values than those selected at random. For example, we want to know whether an embryo that has a low polygenic risk score for hypertension will indeed go on to develop hypertension at a lower rate.
All the people I've heard criticize PGT-P seem to think that the ONLY way to do this is with some kind of randomized control where some embryos with certain polygenic risk scores are implanted and others are not, and we then wait 20-70 years to see whether or not the polygenically screened group develops diseases at a different rate than the control group. I think this view is incorrect and is only taken because people are blindly applying traditional validation methodology to PGT-P without asking whether it is necessary.
Genes have a very special property that gives us a huge advantage over researchers trying to test whether or not a medication works; nature has already conducted a randomized control trial for us!
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