Herasight Health is Herasight's new "health only" product that is less expensive than their standard $50k product, but doesn't include screening for IQ,
Noting that this is a red flag, according to me. Acknowledging that this easy for me to say as someone who is not trying to make a startup work, I think it's bad for reprogenetics clinics in general to be withholding something major like IQ screening from the ("mere") $20k customers.
This is much more important in the long run compared to the short run, so assuming this is a temporary thing that will change soon, it's not that big of a deal. I've always assumed that, initially, advanced reprotech will be quite expensive, and wealthy people will get access first, and then over time the price will drop due to innovation; and furthermore, innovation includes paying off previous expenditures for research, as well as innovation in building out the business in general (not just the science).
However, a big part of the social contract around reprogenetics is that it will be maximally accessible in the long-run, and in particular, it won't create increasing inequality due to economically important traits like intelligence being hoarded. For this reason, assuming it's the case that IQ screening is basically zero additional marginal cost (for a client who's already purchasing the Health product), and given that IQ is such an important trait, the lion's share of the benefits of IQ screening should be made as accessible as possible as soon as possible. I think that making a sharp cutoff, where anyone below the $50k level gets no IQ screening, is probably unnecessary (admitting that I don't actually know the business situation) and is probably too costly in terms of acting out what appear to be the beginnings of a bad longer-term policy.
Even if the business situation does make a sharp cutoff necessary for now, that would be hard for outsiders to know; and in any case, I would like to apply societal pressure to reprogenetics clinics to get rid of the cutoff ASAP. In general, there should be a culture of innovation and accessibility.
(To be clear, it's not solely the fact that it's zero marginal cost; it seems perfectly fine for a company to make money by charging for access to software etc. But IQ specifically, as well as the largest expected impact diseases, shouldn't be sharply withheld.)
It seems, from the sidelines, like there should be a lot of options whereby a reprogenetics company could upsell to people with money. Besides the normal stuff (concierge and custom service, better sequencing and phenotyping, etc.), they could e.g. offer the most up-to-date IQ predictors in the most expensive product, and have a previous open-source model used for the less expensive product that gets most but not all of the predictive power.
Those who enjoyed this post may be interested in attending the Reproductive Frontiers conference on June 16-18 in Berkeley, CA! See the LW post here.
Curated. I am personally interested in using embryo selection if I ever have children. It is quite nice to have all of the relevant information in one place, and to be able to get information for specifically my situation/goals. I appreciate your use of our new iframe feature! Having calculators that let me figure out how much of an effect (and with what variance) I should expect per dollar under different approaches is extremely useful. I hope others find it useful as well. I think there's a decent chance this post causes the existence of a counterfactual (and counterfactually more awesome) person, which obviously warrants curation. Thank you for making it!
Gripe. This doesn't really seem like it is about superbabies, a term which has historically been applied only to really quite unusually smart babies who might, eg, be able to solve the alignment problem or whatever. Diluting the term seems like a mistake to me. If your baby isn't as smart as Von Neumann, it's not a superbaby, merely sparkling genetically enhanced offspring. That said, I am still a staunch advocate for genetic freedom in general, and I am glad this post exists overall. Consider changing the title some?
I debated whether to use the term "superbabies". It has been used by quite a few of my friends who are having polygenically screened children and it a little more legible than the term "polygenic screening". So I ultimately opted to use it for that reason.
Maybe it would have been better to title this something like "How to Have Polygenically Screened Children: 2026 edition".
(As I have told GeneSmith, superbabies is also IMO a mildly toxic term, as it's a bad concept to apply to children. For example, it makes it seem like there's some category here, which there isn't much of, and it makes it seem like a product you're buying ("designer babies"), which it isn't (they are people), and it subtly bakes in a universal notion of good (similar to "enhancement"), which there shouldn't be, and it kinda instrumentalizes / objectifies kids, which you shouldn't do.)
Recommendation for a cheaper clinic:
I got my eggs retrieved and frozen at Reprofit clinic in Brno, Czech Republic, for very cheap. The whole process, including the meds, cost less than 2000 euros. Looking at their price list, IVF with one's own eggs costs about 3300 euros. Not sure about what screening services they offer, or whether it's possible to transport the embryos to have the tests and the transfer done elsewhere.
My experience with them is very good. Nice staff and doctors, the place looks nice (no Eastern European nightmare). They are pretty hands-off, compared to what I've read is routine in the US. I only had 1-2 ultrasounds for my social freezing, and they didn't do any blood tests I didn't explicitly ask for (I specifically asked for estradiol during my first cycle; I didn't bother during the second). I assume if there were complications, they would do more. The retrievals were successful. In two cycles I got 27 good eggs.
Thanks for this, this is a concrete post. So the selection step itself is treated pretty informally. Parents either set hard thresholds or build a weighted spreadsheet and either way we’re collapsing a pretty rich posterior into a single number per embryo, the reports already carry more information than that approach uses. Before touching weights at all, we can drop embryos that are worse on every trait the couple cares about. If an embryo is strictly dominated by another, there’s no preference structure under which it’s the right pick so we can eliminate it geometrically and remove a chunk of “did we pick the wrong weights” regret for free
and when parents do have to weigh the remaining embryos, the usual 'how many iq points equal one percent of schizophrenia risk' framing treats each trait as independent and flattens the variance, I find the fritz story is a nice illustration of the alternative mattering in practice: so the t1d posterior is bimodal because of the protective variant not just low on average and an expected-value comparison would have obscured how onesided that call actually was
Do any of the companies expose the variance on individual predictions or only the point estimates? 9% ± 0.5% is a different decision than 9% ± 4% when the alternative embryo is at 7%, and i’d guess most parents would rather take a lower mean embryo with tight variance than a higher-mean one with wide variance if the report actually let them see that, if the variance is in the underlying predictor but not in the report, that seems like a cheap product fix imo
Do any of the companies expose the variance on individual predictions or only the point estimates? 9% ± 0.5% is a different decision than 9% ± 4% when the alternative embryo is at 7%, and i’d guess most parents would rather take a lower mean embryo with tight variance than a higher-mean one with wide variance if the report actually let them see that, if the variance is in the underlying predictor but not in the report, that seems like a cheap product fix imo
Ok, I've literally checked with the most knowledgeable people in the world on this, and the answer is that prediction error (i.e. the variance in outcomes), does vary a tiny but, but only as a result of differences in the imputation accuracy of each embryo's genome.
Herasight is the only company that does embryo genome imputation at the moment, so this isn't even relevant to Genomic Prediction or Orchid.
Also, thinking about "error" in the prediction only really makes sense for continuous traits like height or IQ. For disease risk, any company worth dealing with account for prediction error in their risk prediction.
A weaker predictor should always produce a disease risk that's close to the population average for that particular embryo's sex and genetic ancestry. A stronger one will show more variance in risk from one embryo to the next.
And this is in fact exactly what you see. There's quite a large spread in the risk of a disease like type 1 diabetes, and quite a small spread for something like epithelial ovarian cancer.
For IQ, the standard deviation of IQ for a randomly chosen embryo would be +-10.6 (15/sqrt(2)). If you know the predicted IQ from Herasight's IQ predictor, that variance shrinks to 9.3 because a portion of the variance is now "fixed" thanks to the prediction.
For example, an embryo with a predicted IQ of +10 would have a narrowed, right shifted distribution compared to an average embryo: https://pbs.twimg.com/media/G6oTYmLbwAI51py?format=jpg&name=medium
And yes, Herasight shows this. Neither Genomic Prediction nor Orchid offer selection on continuous traits right now. I don't know if Nucleus does, but they have other issues such that confidence intervals should probably be the least of your concerns.
I think "superbabies" has historically referred to (close-to-)smartest-ever-humans via reprogenetics, and I think this is a useful term, and should continue to refer to it. This post seems like it's diluting the term, using it to refer to all reprogenetically enhanced children
Open to suggestions that are better than some long phrase, but I don't think "superbabies" is a good term. See: https://www.lesswrong.com/posts/PPLHfFhNWMuWCnaTt/the-practical-guide-to-superbabies-3?commentId=hFj8yTRaMCRo6XpJt
"Genius babies" is better IMO if you must have a term, though it's of course silly (but so is "superbabies"); that's what I say when I'm reaching for this term. "Children whose parents/makers used reprogenetics to make them have very high expected intelligence" is the very long phrase; I'd want a good term for "reprogenetics children", and separately a term like "IQ-increased children", and "superbabies" could be replaced by just combining those two words, though that might be too long. One could use some more florid term like "indigo children". Another issue is that "reprogenetics IQ-increased children" isn't actually all that relevant besides the facts that (1) most very very intelligent kids will likely be reprogenetics IQ-increased kids, later on; and (2) reprogenetics is the way to increase that category.
Quoting myself from here:
The field of advanced reprotech and reprogenetics is not for intelligence amplification, existential risk reduction, or anything about AGI.
(I get, and agree, that legibility is good, but that balances against these other considerations; better lexicogenesis is tugging the rope sideways.)
There may be a better term than superbabies for the thing I want to point to, or the thing you want to point to, but superbabies is certainly a bad term for the topic of OP
Great post!
Regarding freezing immature eggs: depending on the IVF protocol used, the clinic may not be able to see if an egg is mature or not before they attempt to fertilize it. This relates to whether or not they remove the cumulus cells surrounding the egg before adding the sperm. Cumulus cell removal is standard in ICSI procedures (where the sperm is mechanically injected into the egg), but if you're not doing ICSI, the clinic may not be able to separate the immature GV eggs from the mature MII eggs.
So if you want to separate out the immature eggs and freeze them, and you're not doing ICSI, you may need to ask the clinic to remove the cumulus cells a bit earlier.
Fascinating, thank you! I feel that it is important that clear information be available on current options and their effectiveness (independently of one's opinion of embyro screening, societal effects of this becoming commonplace, and if all traits should be made available for selection).
Personally I'd most likely go through with screening for my potential future kids, most definitely for diseases (I cannot imagine intentionally allowing my kids to get preventable genetic diseases) and possibly for other traits as well. I still don't know how much information I'd want to know, or if wanting to avoid knowing traits about my future kids is an illogical cultural vestige. I think it's a topic worth discussing openly, either way. I often see an avoidance of the topic altogether, as if giving it a blanket determination of "immoral" or a "slippery slope" were to make it go away entirely.
Quick question, I've been fascinated by the book "The Vital Question" by Nick Lane for a while, especially his theory that the fact that there are two genders is the result of needing different mechanisms to preserve eukaryotic and mitochondrial DNA within the same cell (while also allowing for some degree of mutations).
This theory tracks with my knowledge of ovarian follicle maturation, in which several follicles go through a competitive growth spurt, and only the "winning" follicle matures into an egg that is released. Basically, the ovaries conduct a monthly growing competition, and the single egg (usually) with the best mitochondria gets the possibility to be fertilized.
This is precisely the mechanism that you bypass with IVF drugs, in order to get multiple eggs to harvest. Instead of follicles competing, every follicle gets to grow to completion and release an egg.
When I learned about this, I thought a nice sanity check about Nick Lane's theory would be to see if IVF has a tendency to lead to disproportionally higher rates of mitochondrial diseases. If Nick Lane's theory is true, disrupting follicle selection should lead to more embryos with low quality mitochondria. I couldn't be bothered to spend too much time on this, so I fired up a ChatGPT Deep research instead, which I will link to below (a little embarrassing as I wrote out my questions quickly, but oh well). The result was that IVF babies seemingly have a bit of a higher rate of genetic disease overall, which is natural seeing as the traditional usecase is for infertile/older couples, but the conclusion from that Deep research was that yes, there is in fact a slightly higher rate of mitochondrial diseases in IVF children! To me, this was quite a delightful validation of Nick Lane's theory, but I didn't have time to properly vet all the studies ChatGPT had dug up, so I left it at that. Also, to my knowledge, IVF clinics have traditionally at least sometimes picked "well growing" embryos, which might possibly somewhat filter out eggs with particularly poor collections of mitochondria.
But reading this, I am struck by the fact that this intensive genetic selection leads to a complete disregard for mitochondrial health. By focusing on genetic predictors that you think will improve health/IQ, you risk disregarding more holistic selection methods like embryo growth rate. I would very strongly assume that the vast, vast majority of the risk factor and IQ related genes that we understand are from correlations taken from population studies, and the vast majority of those populations will not have been born from IVF, and of those who have none from IVF with embryonic selection. So you think selecting from genetic markers will lead to an advantage, but you don't actually know that. To actually know this, you would need a large random sample of the population, randomize them to "regular conception", "IVF", "IVF with genetic selection", and then compare the relative rates of diabetes / IQ and so on. Needless to say no one has or will ever do this particular RCT, and so I think this article is much too strongly worded towards definite positive outcomes. Of course, selecting out SNPs and such is a different story, I am focusing on less cut and dry genetic factors here.
Furthermore judging by the (possible) weak signal for increased rate of mitochondrial disease in IVF children (from my admittedly cursory research), despite the potentially preventive effects of IVF clinics "normal" procedure of watching growth rate, there might actually be some reason to hypothesize that this form of embryo selection would lead to inferior health outcomes as to compared to regular conception. How strong you think this hypothesis should be might partially depend on how important you think the follicle selection process is for mitochondrial health. Evolutionary speaking, seeing as the preservation of mitochondrial DNA might be the entire reason for there being two genders, I would say your priors should be that any process which seems to be related to that is probably pretty important. If not on the timescales of individuals, then definitively so on an evolutionary horizon.
So, I am wondering if there is some counter-evidence to refute my speculations on this topic? It would be a shame if this whole approach turned out to lead to increases in mitochondrial disease that would be compounded with each successive future generation. Mitochondrial diseases tend to be very nebulous also, and are not really clinically evident until things get really bad. Seeing as they are the result of "overall" decreases in mtDNA quality across a large population of mitochondria, with hundreds of thousands of mitochondria per oocyte, you can't sequence them the same way. And so a gradual deterioration would not be evident until a few generations down the line when ATP production crosses the treshold to produce clinical effects which are bad enough to be noticed. Incidentally, this is also why mitochondrial quality and the resulting diseases are not understood as well, and my personal guess is that they are probably a much bigger problem than we think.
Deep research link: https://chatgpt.com/share/6905f481-b850-8010-b163-e329c210fcc4
Interesting question. I don't know about this area so I can't really comment, but I'll just say a couple things.
the conclusion from that Deep research was that yes, there is in fact a slightly higher rate of mitochondrial diseases in IVF children
(Just noting that this conclusion should be treated as preliminary until it's checked by reading the citations or hearing from an expert. I'll assume it's true here.)
a slightly higher rate of mitochondrial diseases in IVF children!
This could also still be selection effects, if mitochondrial diseases are common causes of fertility challenges.
, every follicle gets to grow to completion and release an egg.
I think you're right that there'd be relatively less selection, but I'm pretty sure there's still lots of attrition in the egg retrieval process. Furthermore, I'm not clear that the overal selection pressure on mitochondria is actually less in the case of IVF? You select less on eggs during the egg retrieval, but you're also causing a lot more eggs to grow; and then you do select on "does the embryo grow / become euploid" (though euploidy may be mainly about the oocyte's chromosomal health).
there might actually be some reason to hypothesize that this form of embryo selection would lead to inferior health outcomes as to compared to regular conception
It's reasonable to hypothesize. And definitely definitely these things should be tracked; getting feedback about any sort of reprogenetics is key. (Also, this might be testable right now; for example, if clinics use different criteria for which embryos to implant, some of which correlate with mitochondrial health and some of which don't, we could check relative results.) But overall I'm quite skeptical that you'd get inferior outcomes in most cases. I think (just impressions) that usually mitochondria are fine, and genes are just pretty important to so many health outcomes.
If not on the timescales of individuals, then definitively so on an evolutionary horizon.
I really doubt this would become an issue--for example, you could use mitochondrial replacement therapy.
All good points, I have a few comments on some of them:
"This could also still be selection effects, if mitochondrial diseases are common causes of fertility challenges."
I forgot to write this, but the clincher was that the rate of increase in mitochondrial disease was relatively higher than the corresponding increase in genetic diseases in children born to IVF (although it is a weak signal on top of a shoddy research methodology). It is hypothetically possible that mitochondrial diseases are disproportionately more likely to cause infertility than genetic ones, or that they are more important than previously known in common conditions like PCOS, and that this explains this divergence. However I don't think your priors should favor this conclusion, seeing as this (to my knowledge) is not the current consensus in the field.
Also: "but you're also causing a lot more eggs to grow". Nature also selects a lot of eggs to begin growing, it's just that the ovaries terminate every candidate but one (occasionally two or three) during follicular selection. So nature essentially starts the same process as you do in IVF, but IVF drugs removes the selection mechanism by allowing all the follicles to fully develop and release a ovum. The exact number of follicles that start growing might be higher (I have no idea if this is the case), but seeing as every follicle gets to release an ovum, there is no selection mechanism anymore. The selection pressure is not in the growing, but in the dying. One of the main evolutionary functions of the ovaries as organs is to kill unworthy follicles, and the main weapon at their disposal is cutting off the supply of follicle stimulating hormone (FSH). The very hormone you take as a drug to enable multiple follicles to grow! You flood your system with recombinant FSH, completely neutering the ovaries ability to exercise their judgement, and bypassing what is perhaps THE reason ovaries exist (besides just the fact that you have to put your eggs somewhere). And I don't think this should be dismissed as a minor detail. If Nick Lane is right, follicle selection is the whole reason gender exists. So follicle selection might be, to quote a Lesswrong classic, possibly quite amazingly important.
Although keep in mind there is also a large amount of selection done while growing up, a newborn is born with 4-7 more eggs than remains at puberty, so some selection pressure remains without what happens during follicle selection. My point was that putting less of a focus on embryonal growth rate and more on genetics might inadvertently decrease the selection pressure even more.
As to mitochondrial replacement, I'm not very knowledgeable about the field besides knowing that the cases where it was done were done by transplantation, which I assumed would be hard to undertake at scale. Looking it up, there were just eight performed in the UK in 2025. No doubt largely because of how rarely families are diagnosed, especially in advance of pregnancy, but I would assume it's also technically difficult. I don't know how far we've come with potential alternatives like mtDNA engineering, or if keeping a "culture" of healthy mitochondria is possible. But as a solution it seems unlikely to me to be an "easy fix" without technical breakthroughs. Although I do agree that on longer timescales it is not unlikely to be a solved problem, which probably alleviate my worry about compounding generational effects.
I'd like to stress that mitochondrial disease is difficult to diagnose, and seeing as there is no treatment except for the unborn, there is little incentive to do so either. And diagnosis looks for the extremes, the known mutations. I do not think much is known about the health or cognitive effects of "suboptimal" but not strictly pathological populations of mitochondria. I think there is some reason to not dismiss mitochondrial diseases as "rare", and think of it more of an unknown, which would potentially warrant more caution.
All fair points, thanks. (Except I think we're still a bit muddled on the selection pressures, but anyway I take your point about potentially overly discounting visible embryo health.)
Sorry, I typed the first version of my comment on the go, so it wasn't the best.
I did a pass to clarify my points and improve the language a bit. I significantly altered some sections, in particular about selection pressures. Can you have a look and see if that clears things up?
I suspect we differ mainly on the weight we assign to the significance of the follicular selection process. I don't know how familiar you are with the details of the process, and for me it's been over a decade since I had to study it so some details are hazy. But it's a whole thing, a hormonal and cellular song and dance, a beautiful little microcosm of natural selection.
In any case, that leads me to put a special emphasis on any process that bypasses it entirely, like IVF. I always found it weird that bypassing it seemingly didn't lead to any major visible consequences, but figured that the consequences were probably on evolutionary timescales and that we would figure out genetic engineering before it became a problem anyways. Nick Lane's thesis recontextualized that for me. We haven't been doing IVF very long, and mitochondrial health is mostly invisible, since no one looks for it. In addition they don't (usually) behave like other genetic diseases, since you are dealing with a *population* of cells, that all pass on their DNA as individuals. Loss of function is insidious, as more and more individual mitochondria become "sicker" with each generation, until it crosses a critical threshold.
If follicular selection was mostly about mtDNA all along, than this means that IVF might have large consequences that are just harder to spot. This might become more visible as IVF becomes more common, but seeing as almost no one ever even checks for mitochondrial disease (I say this as a clinician who has never done so or see anyone else do it either) it might be missed entirely. Or perhaps the process of selecting the best growing embryo during IVF, as well as the normal pruning of eggs before puberty, almost entirely guards against this scenario. I'm often surprised at just how little some things in medicine turn out to matter. Like you would think turning off fever would be a huge no no during an ongoing infection, but it mostly seems to have no effect (but maybe that's because the effectiveness of antibiotics muddles the data).
Also, I'm by no means an expert on mitochondrial disease. Although I find them interesting, my experience with them is mostly as an obscure diagnostic headache that me and everyone around me always forgets to think about. So I'd say I'm an authority on the topic of how little clinicians spend thinking about them, but beyond that take my opinions about them with a helping of salt.
Overall, I think it makes sense to worry and to investigate more.
Regarding the selection pressure thing, a couple points:
times as much stimulation. If X is big relative to Y, this is close to 1; otherwise it's substantially less than 1, and is more alarming. IDK how big X vs. Y is, but I imagine X is significantly bigger? IDK.
Your point about the dominance dynamic partially being about coordinating the release of one ovum is an excellent one, and depending on the degree to which that is true it might unravel much of the underpinnings of my argument. Although I find it somewhat unlikely that follicular selection would take the particular shape that it has if there's not a significant element of selection. But I don't really have a reference frame for the possibility space of available strategies for such coordination procedures. Are there any other mammals that do not have follicular selection? Any other animals with any clues? Fish and such just outsource the whole selection shebang, but is egg selection amongst birds comparable? I have no clue.
As to the relative selection pressure, I can think of at least one way to try to do the math. I'm just going off cursory search numbers here, but apparently the peak amount of oocytes is actually prenatally at 20 weeks of gestation, where it's about 6-8 million, this declines to 1-2 million at birth, and 300-500k by puberty. Now, there is an unknown factor here which is the degree of selection pressure before the peak at 20 weeks. Apparently pruning starts as early as week 14, but I couldn't find any established numbers. A rough estimate was apparently that well over half of the original germ cells don't survive to be part of the privileged 8 million oocytes. So let's take that at face value and say that it's somewhere between 12 and 20 million competing candidates initially. There is another unknown here which is that not all of this pruning might mean the same thing. The two main mechanisms are atresia of primordial follicles, and death during meiosis, the latter of which sounds more like the results of gene-related defect. Perhaps the first is more mitochondria related, but there is actually a great deal of cell death going on at this stage all over. For comparison, apparently very roughly 75% of male germ cells die around this period. But they might also be subject to entirely different specific selection pathways that are just unrelated to mitochondria. In conclusion I have no idea how to make sense of this mess. I think it seems reasonable enough to just to add 25% to the previous upper estimate of oocytes at birth to inflate the starting point and call it a day, bringing us up to a nice even 10 million. So using the lower bound of 300k, that gives us roughly 30 times more initial oocytes candidates at puberty then at birth.
Here there is a little snag in the logic, which is that as far as I can tell pruning from week 20 to puberty looks nothing like follicle selection. There is no "growth competition", the cells just die off steadily by apoptosis. What does this mean exactly? No clue. If we accept Nick Lane's thesis that women are all about mitochondria, it's probably somewhat relevant? The connection doesn't seem as phenotypically obvious as it does in follicular selection though, where I think the "best grower" concept intuitively seems related to energy output. Then again mitochondria are also very strongly related to the apoptotic process. So I guess the relevance to mitochondria of all that cell death that happened before follicle selection starts is somewhere between 0% and 100%. Great. Let's cut our losses evenly in the most simplistic way imaginable and just go for a 50% penalty to the initial oocyte count to account for this uncertainty to their relevance, putting us at 5 million or 15 times the number of remaining cells at puberty.
So at this point, when follicular selection starts. How many follicles start growing? Some sources say 3-30. The narrowest I found was 5-20. I'm just going to cut it at a nice looking number once again and say 15. So from 15 candidates 1 emerges. So 15 times less again. Here there is another big uncertainty, which is that out of those 15, how many truly bad candidates are there really? I mean maybe the runt of the litter is a bit off, but the biggest and second biggest are most likely not that different mitochondria wise. So once again let's apply a 50% penalty to the importance of follicular selection, and then 50% again to account for your argument about the fact that follicular selection might have a significant element of coordination rather than selection. Let's round it up for a nice even number of four.
So plugging that naively into your formula for X=15 and Y=4 we get 79% of the selection pressure before follicle selection and 21% during. I'm writing this on my phone so I just had GPT 5.4 do the math, and it also suggested that using the logs of each number is mathematically more sensical for reasons I'm not sure I understand. Anyways in that case it's a 69/31 split instead, so roughly two thirds before and one third during follicle selection.
These numbers mean almost nothing, and have mostly been useful for me in illustrating my profound ignorance. However, the final conclusion of it being "a third" of selection pressure seems like a prudent prior to have, so I'll just anchor mine there for no good reason. At least I can pretend to have done my Bayesian due diligence.
Oh, and GPT-5.4 gave me some lip when I asked for a sanity check:
"Your 50% penalty for pre-pubertal attrition being only partly relevant to mitochondrial quality is fine as a rhetorical placeholder, but biologically it is doing a lot of work".
Fair enough.
Nice. Yeah seems hard to estimate, not least because the major sources of damage probably enter the germline continuously over time. E.g. the proliferation step itself (cell division introduces very very roughly 1 de novo mutation), and steps of oocyte epigenetic reprogramming and maturation, are ongoing during development, adding a trickle of variation in oocyte quality. So the variation that you're selecting on is inherently changing over time. (I guess qualitatively, this would increase the relative importance of the final steps of selection. IDK if this matters quantitatively.)
Anyway, I don't have the bandwidth to investigate more, but I'd encourage you to write a little report for LW if you're interested (just be sure to keep marking where your facts are coming from AI summaries as opposed to being checked from papers). As evidenced by this OP, a lot of people are interested!
Also, you may be interested in attending this conference I'm organizing, featuring lots of experts on related areas: https://www.reproductivefrontiers.org/
I spent perhaps a bit too much of the days bandwidth allocation on this conversation myself, but I'll see if I can find the time during the week to summarize it in case anyone's interested.
Also I would have loved to attend your conference, and its actually during a quiet part of my holiday, but unfortunately I think the 15 hour transatlantic flight might be a little bit too steep of a threshold 😅
A metric I think would be interesting that you could feasibly come up with, based on extrapolating the number embryos per IVF round & the total cost per number of day 5 embryos, is the "cost per probable IQ point added".
As someone in a reasonably financially comfortable position who is nearing the stage of life where one typically becomes a parent, it would be a no-brainer to add, say, ~10 IQ points for $100,000 or similar.
There's obviously a plethora of positive life outcomes associated with that, but (perhaps more selfishly) even a slightly higher IQ is associated with fewer externalizing problems in children, like tantrums, conduct disorder, delinquency, etc.
I'd be interested in hearing your thoughts.
I made you a graph: https://imgur.com/a/v5EXnkf
You could probably do it for even less overseas
Hey, I wondered if you could tell me more about the situation in Australia? IIRC, there are no Australian IVF clinics offering PGT-P, and recommendations against it from medical professionals, but no explicit ban on using an overseas company to obtain this data and then implanting the chosen embryo? (Although I believe choosing the sex of the embryo is banned outright.) Have I misunderstood something about that? Would it be possible in practice, or would you expect that no clinic would allow testing or allow the couple to choose their own embryo? Would it be illegal to obtain genetic data given that it would give information about the embryo's sex (even if that was not used to make the decision)? How do the advances with PGT-A play into this?
No worries if you don't know the answers to these yet! It will be several years before my partner and I are looking to have a child, and the technology and regulation could well change dramatically before then - I'm just considering the possibility of egg/sperm freezing, and whether it would be necessary to plan to go overseas for the process.
Sorry for so many questions, and thanks for the great post!
Taiwan could possibly be an option. They have quite inexpensive egg retrieval (something like $3-4k all in). But you'd have to look into data sharing and/or shipping eggs abroad.
It may be technically possible to do PGT-P in Australia right now, but it's very hard and I know several people whose data is basically being held hostage by the PGT company.
MAYBE you could do it if you could convince them to share the raw PGTA data with you and transfer an embryo of your choosing, but unless you have written pre-approval I wouldn't go that route. Australia can ban you from sending your own embryos abroad.
I would recommend Australian patients fly abroad if they want to do PGT-P.
I'd love to get this changed. If you've got any contacts in Australia I or someone else in the industry could talk to I'd be happy to chat with them. Even if they're not going to allow IQ, it's pretty stupid to ban embryo selection against Alzheimer's or schizophrenia when there's no effective treatment for either.
Are there clinics which do full genetic testing on their egg donors?
Personally from a gay-man-considering-surrogacy perspective it seems like that is the biggest potential uplift. But from what I see on e.g. CNY's website they do that only for diseases and not the whole genome. I guess if the clinics tell us the phenotype (e.g. are they college educated) then that would help.
Or is it possible to screen donor eggs directly? (Maybe expensive).
I can't speak for other PGT companies, but I know Herasight will do genetic testing on multiple prospective egg or sperm donors for clients.
I don't know of a single egg or sperm bank that does this kind of in depth testing by default. They don't even offer basic polygenic scores, let alone expanded carrier screening.
You can't screen egg directly because there's no way to read the genome without destroying it, and eggs only have one copy.
You could in theory reconstruct the donor's genome if you had enough of her eggs, but that would require buying and fertilizing a bunch of them.
It's easiest to just directly ask the donor to get genetically sequenced.
Has anyone been able to actually access Fertilo anywhere in the world? Gameto hasn't returned my emails, same goes for the clinic in peru that was publicized as having a successful birth.
I think I'm weird about the embryo selection ethics. My goal is for every produced embryo without "serious" defects to get a chance at life. If the kid won't see himself as cursed by his genetics (osteogenesis imperfecta, for example), then whatever, let's give the kid a shot. How often do parents basically set a cutoff (any embryo with t1d has a cursed life) and just roll with the first embryo over that cutoff?
I'd be mad if my parents had the option to gene edit me and declined it though.
Has anyone been able to actually access Fertilo anywhere in the world?
Yes, I've talked to one of the doctors in Australia who ran their clinical trial. He's had several patients that have used it.
One of the barriers to access right now is it's only approved for use with low-stim cycles, or "Mini-IVF". Those kind of cycles naturally produce fewer eggs, and more immature eggs. Fertilo should work identically for regular stim cycles, but I don't think there have been any clinical trials for it yet.
Thanks a ton for the response, I think my partner and I are good candidates for Fertilo as trialed, and I'd be really grateful if you could DM me contact info for a someone who may want my business.
Crazy timing, was just going over this with an LLM about the same time this got posted this morning. Do the providers explicitly call out traits like Height and IQ - or just disease risk? Also how does being from a population likely underrepresented in the data affect accuracy (for example I don't see Central Asian in the Herasight drop down).
Herasight does height, IQ, and a few other non-disease triats like eye color and hair color. Stuff like facial appearance or athletic performance aren't well enough understood yet for anyone to offer precitors. They'll probably have personality predictors at some point in the next year or so, but that's TBD.
Nucleus offers stuff like this too, but for reasons explained in the article, I would avoid using them for the time being.
Orchid and Genomic Prediction only offer screening for disease related things at the moment.
Central asians are probably somewhere between east asians, middle easterners, and Europeans genetically, so I'd guess you'd see a reduction of maybe 15-25% in the expected gain for them relative to Europeans.
But in other cases it’s not actually clear which disease is worse or how to think about tradeoffs between them. How exactly do parents deal with this? In practice, there are a couple of methods.
On one hand, embryo selection is going to do a vast amount of good for humanity. Children who would've had deadly or crippling diseases won't. Everyone gets a bit smarter and more capable.
On the other hand, it feels viscerally horrifying to be a parent that has to make these tradeoff choices. I can imagine choosing between some combination of IQ/strength/aesthetics benefits that would provide an expected two units of quality of life and a reduced schizophrenia risk that would provide an expected one unit of quality of life. If I pick the former and the die roll goes badly, I know I'm directly responsible for that, for the rest of my life. If I pick the latter, then, every single time my kid misses the game-winning catch by a hair, or gets waitlisted to his dream school, I think about my paranoia being the reason his life is worse.
Humans didn't evolve to live with that kind of damning empirical guilt. I wonder if there's an opening for a startup where you tell them what your priorities are and they pick an embryo for you, such that you never find out which tradeoffs you made.
tradeoff choices
This doesn't help directly, but I just wanted to note that, as stronger reprogenetics in general is developed, most tradeoffs will go away. (Cf. https://berkeleygenomics.org/articles/Methods_for_strong_human_germline_engineering.html#strong-gv-and-why-it-matters ) Many / most of the traits of interest (disease traits, cognitive capacities) are uncorrelated / weakly correlated with each other, and most of the weak correlations are in the non-antagonistic direction (e.g. low disease risk usually correlates slightly positively between different diseases). That means you can just get very low disease risk across the board, and whatever cognitive capacities can be upregulated, all at the same time.
There would still be some tradeoffs:
If I pick the former and the die roll goes badly, I know I'm directly responsible for that, for the rest of my life. If I pick the latter, then, every single time my kid misses the game-winning catch by a hair, or gets waitlisted to his dream school, I think about my paranoia being the reason his life is worse.
I don't think this is really that much different from parents who blame themselves for their child not performing well on an exam because they didn't sign them up for a private tutor. Embryo selection allows parents to influence the outcomes to some degree, but there's still chance involved both from the remaining genetics we don't understand and from the environment.
Humans didn't evolve to live with that kind of damning empirical guilt.
I think humans evolved to deal with far worse than this. Think about how many children literally died from diseases, predation, and other horrible causes in the past. I think that stuff was way worse than seeing your child miss the game-winning field goal or even seeing them develop some mental disorder. And yet humans survived it.
Humans are strong!
I don't think this is really that much different from parents who blame themselves for their child not performing well on an exam because they didn't sign them up for a private tutor.
I feel like there's a fundamental emotional difference when it comes to genetic limitations, just because of how much more unfair they feel. As you point out, it's not logical - picking the traits that you want for your kid increases their expected happiness in life and is definitely a morally good action.
being the reason his life is worse.
One way to think about it is comparing to the alternative of not choosing. There are tradeoffs, but it's a net improvement over the alternative of a random genome. By going through substantial inconvenience in order to make some genomic choices on behalf of your future child, you're giving them that gift. Maybe it's not the optimal gift, but it's still a supererogatory gift.
If I pick the former and the die roll goes badly, I know I'm directly responsible for that, for the rest of my life. If I pick the latter, then, every single time my kid misses the game-winning catch by a hair, or gets waitlisted to his dream school, I think about my paranoia being the reason his life is worse.
Are you making sure to also account (both in reasoning and in intuition / emotion) for the upsides in both cases? If not, then you're applying a sort of Copenhagen ethics, where you're automatically punished for taking responsibility, compared to leaving it up to random chance.
I think a lot of people do apply Copenhagen ethics, and I sometimes do too, so it's not crazy. But my experience has been that sometimes it becomes just totally untenable to have no one taking responsibility, so you have to do it yourself. And then you have a bunch of difficult fast-paced choices where any option can be criticized. I think this situation is probably basically necessary as parent (though I'm not a parent)? Like, there's just a ton of choices (what food? what water filter? what books? where live? what about phone / screens? school? rules? enforcement? etc. etc.), and you have to make some choice, and they all have flaws, but it's ok, you're doing your best--that's the standard, not "was I totally blameless for all bad outcomes".
being the reason his life is worse.
Another way to think about it, is making your best guess at what he would want. Of course, this doesn't really answer any concrete question, but it's maybe a slightly different stance. If you could, you should give him control over his own genome; but that doesn't make sense because he doesn't exist yet. ( https://berkeleygenomics.org/articles/Genomic_emancipation.html#appendix-the-origins-of-souls ) One way to try to compute what he'd want, is to ask what you'd wish your parents would have done for you.
What is the tradeoff between having a baby now and waiting a few years? Like if I have a baby now with the current technology, how many IQ points, risk of Alzheimer or depression etc. will the baby miss out on if it was instead born in five years?
Also, how is similar technology but for adults coming along? Do you think it the case that it doesn't really matter when you have kids because you can do gene therapy (or something like that) to adults that will give the same benefits?
What is the tradeoff between having a baby now and waiting a few years? Like if I have a baby know with the current technology, how many IQ points, risk of Alzheimer or depression etc. will the baby miss out on if it was instead born in five years?
Right now you can get about +8 points of IQ from 10 embryos. A theoretically perfect predictor could get you about +13.
For Alzheimer's it's probably a similar gap between current and theoretically optimal.
However I don't think we're going to hit the ceiling of max gains in the next few years. We need way more data for that and no one is on track to gather that much.
My guess is IQ gain might get up to 9 or 10 in the next couple of years, and we'll continue to see marginal improvements in other stuff like diseases.
The tech for adults is much harder. We continue to see improvements in therapeutics for a lot of things like high cholesterol, cancers, etc. So I'm hopeful those will actually make many of the diseases we can currently screen for much more treatable in a few decades.
As for doing genetic modification in adults, we've got the most rudimentary possible stuff right now. Probably the most interesting one from a layperson point of view is Verve-102, which knocks out PCSK9 in the liver, permanently lowering cholesterol. I think this would likely have positive impacts for almost anyone who got it, though the largest benefits will accrue to people with a family history of high cholesterol.
For more systemic, polygenic stuff, the best bet is probably something like what R3 Bio is doing growing "organ sacks". If you can grow new organs (or potentially even a new body without a brain), you could genetically engineer it to be resistant to almost any disease you can think of.
I want to write more about this before too long.
Options are great, as long as you can predict the long-term group-consequences of your individual preferences. We didn't get a certain distribution of traits by accident, it is part of an evolutionairy proven model of distributing properties among people so that on average, we'll be making progress. So, if we tweak the distribution of traits, we might end up in a not easily reversed suboptimal situation. A society with all leaders or all scientists would be likely pretty horrible. For practical reason, most people need to be followers. You need a reserve of psychopaths for when shit hits the fan (societally speaking).
Also, I don't think you can eliminate suffering in general, you can only shift the boundaries of what's considering suffering.
Options are great, as long as you can predict the long-term group-consequences of your individual preferences.
We don't apply this standard to other technologies or other sectors of life such as public policy, state structure, social norms, language, institutions, diet, etc. What seems to work are things like:
These don't involve directly predicting long term group consequences, because that's infeasible. Instead you heal what's in front of you.
We didn't get a certain distribution of traits by accident, it is part of an evolutionairy proven model of distributing properties among people so that on average, we'll be making progress.
It sounds like you think there's something especially good or ideal about the default evolutionary pressures. Is that right? If so, why do you think so? It seems fairly unlikely. I mean, there's clearly something kinda good about them, in that e.g. they tend toward empowering people at least somewhat, and on some very long timescale we'd expect some degree of niche-filling. But there could just as well be poor incentives. Human-evolution, like all species-evolutions, just greedily picks allele-frequency-increasing alleles given the current environment and gene pool; no strong reason for that to be aligned with our humane values.
So, if we tweak the distribution of traits, we might end up in a not easily reversed suboptimal situation.
I think this is possible in theory, and we should avoid this (e.g. with strong norms against such genomic choices, and maybe international treaties about it). I think it's quite unlikely because (1) we don't know much about genetics of personality (2) even if we did, personality is probably quite variable anyway, and (3) there will be a huge spread of who uses reprogenetics at all and what genomic choices parents will make, both in a given year and also as time goes on, and (4) the gene pool has a huge reservoir of variance and (5) what you do with reprogenetics can usually be reversed to a significant extent and (6) we can get multigenerational feedback. This adds up to "effects on mean traits of populations are quite weak for a long time, except for increasing some tails (and, possibly, with very large uptake of basic reprogenetics (e.g. embryo screening), decreasing some downside tails (e.g. severe monogenic diseases))".
A society with all leaders or all scientists would be likely pretty horrible.
Eh, IDK about horrible. Seems not ideal, sure. Scientists can lead and leaders can science.
For practical reason, most people need to be followers. You need a reserve of psychopaths for when shit hits the fan (societally speaking).
I'm not convinced, why do you think this (compared to hypothetical alternatives, such as figuring out good healthy sane humane competent leadership)?
Also, I don't think you can eliminate suffering in general, you can only shift the boundaries of what's considering suffering.
That's all well and good, but I think quite a lot of people, myself included, would rather set up future children for the kind of suffering involved in not knowing which groundbreaking intellectual or artistic effort to invest in, rather than the kind of suffering involved in cystic fibrosis and Alzheimer's.
Thanks for your throughts!
We definitely don't apply that, but my point was not if they are applied or not, its that a certain freedom in options can come with a cost that isn't borne by the individual, and we need to look beyond the individual to properly balance those. Empowering individuals can be great for certain situations, but bad for others. Healing what's direct in front of you is the best option if long-term consequences are murky: at least you create a short-term gain.
I don't think evolutionairy processes are good, merely that they are a natural extension of certain optimizations. By looking back at such things, we can see why they came about. I feel the same about culture: those are a lot of guidelines how to do things without explaining why we need to do it that way. Discovering the why helps us identify which things we need to keep and which are evolutionary bagage.
I have enough experience with personality types and group dynamics to have experienced the disasters that come about by having just leades and no followers or planners and no executors in a group or organization. It will fail.
I 'm also not convinced we need psychopaths. Personally, I'd rather not have them. But, I simply have to admit I don't know enough about why they are there. Removing them might be like removing maggots from a festering wound: you'd rather not have them, but if you don't know the science behind what they are doing, you might remove them merely based on the feeling that you don't like them,
First off, nice that you got to hold a baby. Also, nice to want to improve the screening for diseases.
Importantly, there is limited evidence supporting almost all the claims, however well intentioned. That PGT-P improves real-world child health outcomes in a way that justifies its routine use is unproven, as is that it reliably predicts or increases intelligence in any practical or meaningful sense (that's before we even consider IQ as only a reliable measure of a narrow construct - where is the reliable measure of creativity, practical judgment, personality, motivation and all the other social skills?). Where are the citations, sources, independent studies, peer review? Where is the data in the graph from?
And super babies? Ranking embryos? It feels like market-driven eugenic thinking. I thought we'd moved on from that early to mid-20th century aberration.
"Importantly, there is limited evidence supporting almost all the claims, however well intentioned. That PGT-P improves real-world child health outcomes in a way that justifies its routine use is unproven"
I hear this claim repeated often by people in the field, most of whom seem unaware that there are multiple papers validating polygenic scores in a within-family context. Just to list a few:
Lello et al Wolfram et al Moore et al Plomin et al Selzam et al
Maybe you're still thinking "that doesn't prove these actually work in a clinical context". But we already have polygenic predictors deployed in clinical practice, such as Myriad's breast cancer predictor.
But maybe you're still not convinced. Maybe you think "we need to wait for a bunch of selected embryos to grow up, then observe whether or not selection worked." In that case, I'd just point out that this dataset already exists: it's called "siblings", and it can show you exactly how well predictors perform on selecting an embryo with a lower risk of breast cancer or a higher predicted IQ.
"where is the reliable measure of creativity, practical judgment, personality, motivation and all the other social skills?"
The biobanks from which these predictors are trained have not yet deemed it worthwhile to examine the genetics of these other traits. So for the time being, we're limited to diseases, IQ, height, and (maybe soon) personality and possibly facial appearance (the latter is still speculative at this point).
The other things you pointed out are of course important too. Motivation is, I think, particularly important. We'll likely be able to test for this weakly soon via conscienciousness. But there are just obviously many other important human traits that we don't have good predictors for at all. I think it's a shame.
But the only way to solve this is with more data, which is too expensive to collect for the moment.
And super babies? Ranking embryos? It feels like market-driven eugenic thinking. I thought we'd moved on from that early to mid-20th century aberration.
Was anyone signing up to be part of 20th century eugenics? Of course not. It wasn't a voluntary process at all. It was state sponsored sterilization and murder.
If you don't see the difference between that and embryo selection, you either haven't thought deeply about it or you're catholic.
If it's the latter, I understand. One day we'll have a way to do this without any excess embryos. But not yet.
Regarding the last section, I think you're being quite dismissive, i.e. not addressing their concerns and acting as though they don't have legitimate concerns (while I think probably not in fact understanding their concerns). For example,
If you don't see the difference between that and embryo selection
I mean, did they say "there is no difference between embryo selection and state-enforced murder"? I think you're strawmanning them.
If you don't want to deal with these sorts of comments, fine, that's understandable, and there's a lot of other valuable things that you do such that you don't need to work on addressing these sorts of comments with more attention. As I've said repeatedly, I AM VOLUNTEERING TO GIVE THOUGHTFUL RESPECTFUL REAL ANSWERS TO MORAL/ETHICAL CONCERNS ABOUT REPROGENETICS. Please just tag me instead! I imagine (not confidently, but this is my top guess when I quickly try to empathize with you) that you're doing a social motion that's something like demonstrating+performing confidence / power, like "yeah actually I'm right, I know I'm right, I know lots of other people agree with me, and I'm expecting lots of people to back me up on this, now and then even more in the future". I think that's fine and in some cases good to do, as a general category. But I think that doing it by strawmanning and dismissing is bad. I think that you think that (or act as though) if someone can't express their concern very clearly, and so you can give a shallow counterargument that they can't quickly give a compelling response to, then that's a win. I think that it's sometimes a win and sometimes a loss, because if the version you're doing is strawmanning them, then they have a concern which you haven't addressed but you've put them in a position where their (fumbling) attempts to get their concern (however coherent or not it may be) addressed are met with dismissal or even derision, and no easy recourse for more helpful engagement.
This is a fair critique. I think I’ve partially ended up training myself to respond too dismissively by spending a lot of time engaging with the attention dynamics of Twitter.
Was anyone signing up to be part of 20th century eugenics? Of course not. It wasn't a voluntary process at all. It was state sponsored sterilization and murder.
If you don't see the difference between that and embryo selection, you either haven't thought deeply about it or you're catholic.
If it's the latter, I understand. One day we'll have a way to do this without any excess embryos. But not yet.
Speaking as an actual Catholic, I do see that you are at least trying to avoid sterilization and murder (by not applying them to those that you recognize as persons). However, I also believe that you are failing.
If an unusually enlightened Nazi eugenicist said that destroying "life unworthy of life" was to be only a temporary endeavor, to be replaced at the first opportunity with nanotechnological bio-engineering to fix defects in those newly born with them, I expect you'd find it insufficient as justification or reassurance.
I suppose (though the above argument does not rely on it) that you want "Superbabies" to align artificial superintelligence and thus save the world, and that this accounts for your urgency, without which there would not be even an insufficient defense for what is proposed here (at least, not from a Catholic perspective).
I want to save the world too, but that does not justify treating human embryos (can you prove that they are not persons?) as mere means to that end. It is too easy to let messianic ambitions blind oneself to the requirements of humanity, as history can attest.
Finally, apologies for the late post - I understand if you do not reply. Also, apologies if this is written in an overly persuasive tone - I have tried at least to be honest. I pose one more question: Do you believe that you are different from historical case studies in overreach, because you have a better understanding of science, or of morality, or because you have a better cause (supposed by me to be aligning superintelligence), or because your actions really are different?
I think my current view on the moral value of embryos is an extension of my views on the moral worth of fetuses and the morality of abortion. I think abortion becomes worse and worse as the pregnancy goes on because the fetus comes to more and more closely resemble a human.
At the stage of an embryo, there's just not much that appears to me as "human" about an embryo that I would recognize as having moral value. There is potential, sure. but there is also potential in a human egg, and very few people consider an egg to have moral personhood.
To really posit otherwise, you almost have to believe in souls, or some other kind of binary identifier of personhood that comes into existence at a discreet point in time.
It's probably worth noting that Catholics themselves don't seem to have a universally shared view on the question of when exactly ensoulment happens. Theologians like Robert George seem to have settled on "fertilization", but others like Thomas Aquinas seem to have believed that it occurs later, perhaps at implantation or when an embryo develops sufficient biological organization.
Maybe this is all besides the point. It probably doesn't matter that much what Aquinas thought if you yourself believe that ensoulment begins at fertilization.
I suppose (though the above argument does not rely on it) that you want "Superbabies" to align artificial superintelligence and thus save the world, and that this accounts for your urgency, without which there would not be even an insufficient defense for what is proposed here (at least, not from a Catholic perspective).
I suppose if I thought genetically enhanced humans were the only way to save the world, I might consider it to be "worth it" even if I shared your ethics. But at the moment I think it's quite unlikely the "superbabies" path will have enough time to pay off before someone creates digital superintelligence. And I don't think we are doomed with certainty by default.
My real belief is that embryos don't have moral weight beyond their potential to become a child someday. So to answer your question:
Do you believe that you are different from historical case studies in overreach, because you have a better understanding of science, or of morality, or because you have a better cause (supposed by me to be aligning superintelligence), or because your actions really are different?
Yes, I do think I have better morality than those who participated in cases of historical overreach. I certainly still have my flaws, but when I think about cases where I am likely to be failing morally, my mind goes to eating factory farmed meat first rather than to discarding embryos.
There is perhaps a chance I am nonetheless wrong. I've written up a proposal on how to do "Pro-Life" IVF better that I think someone of your moral persuasion should probably try to implement in IVF.
Thanks for your reply.
From the linked proposal:
Personally, I have never found this line of thinking particularly compelling. An embryo, as created in IVF, is a ball of about 100 stem cells. It has no heart, no brain, and no circulatory system to speak of. It doesn’t even have a digestive tract. There is little to distinguish it from any other random clump of cells other than its unique DNA and its potential to become a person if implanted in a receptive uterus.
Some people might believe those two facts alone means an embryo already qualifies as a human. But I view implanting the embryo the same way I view having sex; it’s a necessary part of the process of procreation, and you don’t get a baby without it.
I see the appeal of the idea that implantation is required for personhood - as far as I know, the embryo will not activate its developmental program beyond a certain point without it.
But this makes sense for the embryo - without implantation (again, as far as I know) the embryo cannot gain mass. Trying to develop further without implantation would be utterly futile.
I see the dependency of an infant as analogous, though admittedly less extreme. An infant without breast milk or a reasonable substitute will starve, and you will never see the later parts of its developmental program. It would be a mistake to see the infant as only potentially human, and I believe it would be a mistake with the embryo as well.
I believe the example of IVF to be inherently pathological, but I will use it here. An IVF embryo (correct me if I am wrong) has largely the same developmental trajectory whichever woman it is implanted into, provided that the pregnancy is successful. Nearly as much as identical twins normally resemble each other, the infants resulting from implanting an identical pair of embryos into different women would resemble each other. Hence implantation, though essential, does not determine identity in the way that which sperm cell fertilizes an egg determines identity. And I think that continuity of identity is a reasonable basis for assessing human personhood.
And super babies?
I slightly agree that the term and concept "superbabies" has some affinity with eugenical thinking, and is kinda bad (see my other comments on this post).
Ranking embryos?
Note that it is, and very much should be, parents who are ranking the embryos. Clinics provide predictions broken out by each specific condition or trait; parents make choices based on that, however they see fit.
It feels like market-driven eugenic thinking.
I'm not totally sure what you're saying here, and would be curious for you to unpack it. A guess I'd make is that you're thinking something like: "Social/economic incentives about traits/types of people will push parents to make genomic choices for their future children that respond to those incentives; in particular, whatever the strongest incentives are, though incentives would induce all parents to make the same genomic choices in response. In effect, this is some single force (the aggregate of the main economic incentives) making a decision about what sort of person should exist that gets applied uniformly across all of society. That's basically eugenics." Is that close? How would you correct this?
If that's roughly what you're thinking: I almost agree that this is a kind of eugenics, but I don't quite agree. Eugenics was a highly varied ideology so it's hard to analyze, but my attempt is here: https://www.lesswrong.com/posts/yH9FtLgPJxbimamKg/genomic-emancipation-contra-eugenics#The_Eugenical_Maxim_as_the_shared_moral_core_of_eugenics_ My hypothesis there is basically that eugenics largely boils down to "There are Good and Bad traits (a single universal concept); they're important; so we should push for all children to have Good traits.". So, the uniformity is important, but at least according to me, truly eugenical thinking is about justifying a universal application of one standard of Good traits based on conceiving of a single universal notion of Good traits. Responding to incentives could (if extremely pervasive) be a uniform/universal application of one standard, but it's not necessarily being justified that way. This matters because the justification is where much of the really bad stuff comes from. If you put a lot of stock in your single universal notion of Good traits, then you can justify imposing that notion on other people, even using force.
That said, a free market could result in that universal notion of Good traits being justified as such--in other words, people could start blaming children for being economically unproductive / burdensome because they weren't sufficiently genomically optimized. That would start to shade into "soft eugenics", which is still less bad than coercive eugenics, but is bad, and could then shade into coercive eugenics. For example, people could say "why should we provide you healthcare, when your disease is genetically preventable and your parents refused to prevent it for no good reason". (In an absolute sense, in the grand scheme of things, I don't think this is that much of a problem; there's really a ton of latitude (legal and social) in our society to take a huge variety of approaches toward life and child-rearing, though things seem like they've gotten significantly worse in the past decades--but as long as there is this store of liberty, I think the consequences aren't that bad. I'm also skeptical that how much healthcare our society provides is all that linked to which options specific parents would have had to avert sickness.)
Now, even if you agree with my analysis about eugenics and eugenical thinking, you might still be concerned simply about any sort of pressure that applies some human-judgement standard to the genomes of future children. E.g. you might think that are notions of "intelligence" are so deeply flawed that a kid selected to have a higher IQ in expectation would also tend to have some bad quality in expectation. Or you might be concerned about negative consequences of uniformity, regardless of the attendant social attitudes (eugenical or not). E.g. you might think that selecting for IQ would make kids who all have "the same kind of intelligence", and that would be bad. Are these your concern?
that's before we even consider IQ as only a reliable measure of a narrow construct - where is the reliable measure of creativity, practical judgment, personality, motivation and all the other social skills?
Let me know once you find a reliable measure of those constructs with enough DNA data attached to make a predictor :)
Importantly, there is limited evidence supporting almost all the claims, however well intentioned. That PGT-P improves real-world child health outcomes in a way that justifies its routine use is unproven, as is that it reliably predicts or increases intelligence in any practical or meaningful sense
What type of evidence would change your mind?
For most parents, learning to cook and eat healthy should have stronger impacts than these genetic methods.
At 1% the cost.
If you went from being an alcoholic to not, I would agree. But given how messy and conflicting the evidence on nutrition science is, I'd actually guess this is not generally the case. At least not unless you have some major nutritional deficiency.
Maybe you could argue that to be the case for exercise; the effects of exercise are huge and almost no one gets enough to be optimally healthy.
I appreciate the write-up. It's very informative. Apologies if I missed it, but what sort of guarantees or warranties do these companies have? I know it's about probabilities, but if I had a kid via one of these methods and they ended up getting X disease even when I selected an embryo that had like 12% vs 25%, I'd be peeved especially if I'm plunking down $100k. Do I just sue, or can I get my next kid for 1/2 off?
This isn't even talking about them implanting the wrong embryo. I'd probably recommend people to sequence their newborns to verify. Too many memories of sensational news articles about sperm bank fraud.
Another company that has been doing this is mine, Progenic Genomics (https://progenicgenomics.com/). We've been inferring embryo genomes from parents for several years. While we only offer absolute risk scoring for disease traits, we do offer the reconstructed genomes of each embryo, so customers can pursue other analyses. Our prices are designed to be very low (we are focused on NHS / mass-market affordability) and offer scoring for donors as well. We'd love to work with a donor agency on this. You can also reach the president of the company directly (me, mid career technical PhD, if helpful for communication). I hope this message complies with the terms of the blog, if not please let me know. --Brad
For patients starting from a higher genetic-risk baseline (e.g., post chemo/TBI), does embryo screening yield higher marginal benefit due to increased variance between embryos, or does elevated de novo mutation noise reduce effective selection signal?
I was today years old when I found out the average IQ is only 100 and... well, that explains a lot, actually.
Thanks for the post!
IQ is normalized to mean 100, standard deviation 15 from a sample population of test takers, usually matched by age. The mean is set to 100, by design.
Technically, since widely used norming populations are usually drawn from developed countries and exclude people with severe disabilities, the "actual" mean IQ, if you were to test everyone in the world, is lower than 100.
Setting aside whether any of the tests' narrow set of measures says anything constructive or useful about human beings at all.
The positive manifold between different cognitive tests (which is what IQ actually is) is one of the most widely replicated findings in psychometrics. It predicts everything from your grades in school, to your odds of getting into a graduate program, to your lifetime earnings, to your odds of getting divorced.
It's more strongly correlated with some things vs others (for example it's more predictive of school grades than it is of income), but it's one of the single most important factors influencing the trajectory of your life.
Obviously there are many other important aspects of life, but IQ influences a lot of them!
It’s Summer of 2025. I’m standing in a grass covered field on the longest day of the year. A friend of mine walks towards me, holding his newborn son.
“Hey, I don’t know if you’re aware of this, but you were pretty instrumental in this kid existing. We read your blog post on polygenic embryo screening back in 2023 and decided to go through IVF to have him as a result.”
He hesitates for a moment, then asks “Do you want to hold him?” I nod.
As I cradle this child in my arms, I look down at his face. It feels surreal to think I played a part in him being here. It's the first time I've met one of these children that I've worked so hard to bring into existence.
My mind wanders back to a summer five years before when I was stuck at home during COVID, working my boring tech job selling chip design software for a large company. I remember the feeling of awe I had upon learning that it was possible to read an embryo’s genome and estimate its risk of conditions like diabetes, then choose to implant an embryo with a lower risk.
I remember the struggle of trying to break into this new field of reproductive genetics, one I knew nothing about. I remember the endless hours reading research papers, doing computational modeling, the meetings, the flights, and the endless debates about the ethics of trying to bring children like this into the world.
As I stand there in the shade of a large oak tree, the wind gently blowing past us, it all feels oddly distant. I watch his tiny little fists clench and unclench as his eyes drift back and forth gazing at the branches above us.
“You have no idea how loved you are little man”, I think to myself. “Or how many people that you will never meet worked to make it possible for you to be here.”
I hope some day he will understand. He’s among the first of a generation of kids that will have a chance to grow up a little healthier, a little smarter, and hopefully a little happier than the children that came before him. Maybe someday most children will be like him.
In just the last two years, I’ve watched polygenic embryo screening, the technology used to make this possible, explode in popularity among my social circles. A good third of my friends are now doing IVF just to get access. Almost every month there's a record number of new parents signing up.
Everyone has a different reason for wanting it. Some have a family history of some disease and they really don’t want their kid to get it. Some want to make their kids smarter. Some really want a girl.
By now, I’ve chatted with dozens of parents going through this process. They gather together at dinner parties in San Francisco, or in Signal group chats and excitedly go over the scores for their latest round of embryos. They trade tips for how to get medications cheaply, which IVF doctors to go to, and what supplements to take.
There are a million little things to learn. Some IVF clinics can get you twice as many embryos as others. Some are a third of the price. Some will literally fire you as a patient if you tell them you are doing embryo screening.
And then of course there are the genetic testing companies themselves, which have major differences. One of the companies has significantly better genetic predictors. One is much cheaper. And one spent four years misleading its customers about their genetic risk, and trying to cover it up.
Over the past half decade, I’ve worked at two of these companies, started and ran an embryo gene editing company, co-founded a company that helps parents find the best IVF clinic, and helped dozens of parents go through embryo screening. I’ve learned quite a bit about this technology, what it can and can’t do, and how to optimize the process. I’m going to tell you what I’ve learned along the way.
How large are the benefits of embryo screening? Is it even worth going through IVF?
Embryo screening (also known as PGT-P), can increase expected IQ by about 4-10 points, increase life expectancy by about 1-4 years, and decrease the risk of many diseases by about 10-85%. It can also make your kids taller, reduce their risk of mental health disorders like autism or schizophrenia, and (probably within the next year) make them slightly more extroverted or less neurotic.
Exactly how large are the benefits? It mostly depends on two factors: how many embryos you have and the strength of the genetic predictors you’re using to select one.
The strength of the genetic predictors mostly depends on which embryo screening company you use and your genetic ancestry. The number of embryos you get depends on how old you are, how many rounds of IVF you go through, and how well you respond to stimulation protocols.
But these are just words. To help you better estimate the benefits given your own situation, I’ve embedded a calculator below. Keep in mind this is showing expected benefit, and that in your specific cycle the benefits could be higher or lower.
Most parents care about more than one trait. Many will care about having a smart kid, but almost everyone cares about mental and physical health. So how does this work in practice?
The answer is you get a report showing how each of your embryos scores across multiple dimensions, and you choose which tradeoffs to make. You can see what that looks like by clicking the "Display all traits" button in the calculator above.
An actual report from one of the companies will look something like this:
Embryo 9, for example, has a slightly increased IQ, a slightly elevated risk of ADHD, an average risk of bipolar disorder, and a very high risk of schizophrenia.
How do parents decide whether a few extra IQ points are worth the increased risk of those other disorders?
In this case the choice is actually pretty clear; a 9% lifetime risk of schizophrenia is probably not worth an extra point or two of IQ, so almost all parents are going to deprioritize this embryo for transfer.
But in other cases it’s not actually clear which disease is worse or how to think about tradeoffs between them. How exactly do parents deal with this? In practice, there are a couple of methods.
The nerds use spreadsheets. Anfei Larkin has written about how she and her husband went through every trait and disease the company offered and tried to reason through things like what percent extra lifetime risk for Alzheimer’s balances a one percent decrease in lifetime risk for bipolar disorder.
In the end, they averaged their weights for each trait and plugged all the numbers into a spreadsheet to produce a final ranked list of the embryos.
Most parents are not quite this meticulous. The majority of those I’ve spoken with do something like rule out embryos that have exceptionally high risk of serious diseases, then pick the remaining one that scores best on one or two metrics they care about most (usually IQ or a specific disease that runs in their family).
One of the interesting things about embryo screening is that average risk reduction doesn't always tell you the full story. Sometimes the risk reduction can be substantially larger or smaller than the numbers might suggest. I’ll tell you an interesting story to illustrate why.
When averages don’t work
Marshall and Victoria Fritz are a couple I met through Herasight, one of the embryo screening companies working in this space. Victoria has type 1 diabetes, a condition she is hoping to not pass down to their children. Genetics play a major role in T1D, and most people that have the disease possess two high risk variants in their HLA gene, an important part of the immune system.
Victoria is no exception. This would usually mean her children would be at elevated risk of the disease. Embryo screening is already a great tool for reducing T1D risk. We understand the genetics of the disease better than almost any other polygenic trait.
But for Victoria, embryo screening wasn’t just good. It was incredible.
You see, Victoria happened to marry the perfect guy. Her husband, Marshall, has the single most protective T1D genetic variant that we know of. One that reduces the risk of the disease by about 97%.
As a result, they have four embryos that are almost guaranteed to avoid the disease.
This will sometimes be the case for specific diseases where single genetic variants have large impacts.
At least two companies in the space, Herasight and Orchid, offer products that allow parents to get sequenced before they commit to paying the full price for embryo screening. If you’re specifically interested in screening against a particular disease, it’s plausibly worth booking a call with one of them to figure out if the disease you’ve got in mind has this property.
Here’s an incomplete list of these kinds of diseases where knowing the genetic background of you and your spouse ahead of time can be unusually useful:
How much does IVF cost?
For most couples with a woman in the 25-35 age range, you’ll need to go through 2-4 rounds of IVF to get enough embryos to select from. Each of these rounds will cost $14,000-$40,000, with the variance coming almost entirely from which clinic you choose to go to. You’ll then have to pay for genetic testing, which is an additional expense of about $7000 to $70,000 depending on what you want to screen for and how many embryos you have. In all, most people will pay $55,000-$150,000.
The two biggest cost drivers are your choice of IVF clinic and your choice of genetic testing provider.
IVF clinics have pretty significant variability in cost, with the lowest ones being around maybe $14,000 per cycle and the highest being around $40,000. In a typical medium to large size city, costs will look something like this:
Hat tip to Sam Celarek for calling up a dozen IVF clinics in Boston to gather this data.
These costs can often be spread out across a number of years. If you’re a single woman or you’re not certain who you want to have kids with, you can freeze your eggs for about half the cost of freezing embryos, and postpone paying for embryo creation and testing.
You might think that clinic cost reflects clinic quality. And while there’s some truth to that, it’s not strictly the case. Some IVF clinics are quite a bit more cost-efficient than others. A year ago, my friend Sam Celarek put together this graph of expected cost per child at different IVF clinics in Boston after combining data from his clinic success rate model with pricing info he gathered by calling a bunch of different places in the city.
The actual price per child for couples without infertility will be a bit lower than this (Sam built this graph using success rates from infertile women), but the data reflects something real: some IVF clinics are much more cost-effective than others.
How to find an IVF clinic
This naturally raises an important question: which IVF clinics are most cost-effective?
You can ask Sam for access to his data, but one obvious contender is CNY Fertility, a low-cost clinic with branches in Georgia, Florida, Colorado and New York. You can do a round of embryo freezing with them for about $15,000 including the cost of travel, medications, monitoring and the procedure. You can also do egg freezing for about $6500.
CNY’s overall success rates are a bit below average in Sam’s model, but this is probably somewhat confounded by the types of patients it attracts. They’re well known for taking basically anyone, including patients other clinics will outright reject. Sam has tried to factor this in by controlling for differences in patient age and a few other variables when comparing clinics. But it’s not yet possible to control for everything, and my best guess is this is dragging down their numbers a bit.
Still, you’re more likely to need to do an extra round at CNY than at a top tier clinic.
So where should you go if you want the absolute best results? What’s the best path if money is no object and you're willing to pay more per embryo to get the whole thing over with faster?
In that case, the best doctor I know of is likely Dr. Aimee, a fertility doctor in San Ramon CA who has done IVF cycles for many of my friends and seems to generate outlier results at a surprisingly frequent pace. One woman I know who went to her managed to get 17 euploid embryos from a single IVF cycle, an embryo shy of the highest number I ever saw while working at Genomic Prediction. She’s also been able to get a really crazy result for a friend of mine that had infertility issues: this friend had done 6 prior rounds of egg retrieval, getting 0-1 euploid embryos each time, until she went to Dr Aimee. She then had one round that produced a single embryo, after which Dr Aimee added a particular medication to her retrieval process. Her next two rounds produced 5 euploid embryos each time, which if you know anything about IVF outcomes, is an insane jump.
Her prices are on the higher end, but if money is less of a concern for you and you're in the bay area, she's likely worth it. I don't know her exact prices, but it seems to be between $25k and 40k per round.
None of this is a guarantee by the way. My sample size for the above statements are based on outcomes from about ten women.
What about if you’re not in the bay, and you don’t want to travel?
In that case, your best bet is picking a clinic using Baby Steps IVF. Baby Steps IVF was built slowly over the years following publication of my original guide to having polygenically screened children based on research I had done into the success rates of different IVF clinics in the US. Sam Celarek took my raggedy model published in 2023 and turned it into a proper machine learning model using much more advanced statistical techniques and additional data from both SART and the CDC.
It’s now probably the single best resource online for quantifying how good different IVF clinics are. And we’ve made the basic clinic rankings available for free.
Thanks to a lot of work from him and Roman Hauksson and a grant from Astral Codex Ten, this has now become an accessible resource for anyone going through IVF.
I’ll have more to say about Baby Steps in a future post.
Which PGT company should I use? What are the advantages of each?
I should start this section by noting that during the process of drafting this post, I joined Herasight, one of the four main polygenic embryo screening companies. I also have a small amount of stock in Genomic Prediction where I was previously an employee in 2022.
Nonetheless, I’ll do my best here to provide an objective analysis of the current state of the industry.
There are four main companies offering polygenic embryo screening, and a fifth newer one that just got started recently.
The four main players are Herasight, Orchid, Genomic Prediction and Nucleus. The fifth company is Reticular, which is hoping to apply techniques used to create interpretable AI for biology to embryo selection. They're quite new and to the best of my knowledge haven't published any validation papers, so the rest of this post won't mention them.
The shortest summary ever of the four main players is: Herasight has the best predictors and offers selection for the most things but is expensive, Orchid is good but is also fairly expensive, Genomic Prediction is not quite as good but is the cheapest by far, and Nucleus is sketchy and should probably be avoided. I've included a slightly more detailed table below and a much more detailed writeup in the rest of this section.
Quick comparison table
Herasight
Orchid
Genomic Prediction
Nucleus
Predictor strength
Strong
Good
Good
Unclear, misleading estimates for many traits/diseases
Predictors validated within family
✓
For some diseases
For some diseases
For some diseases
Screening for non-disease traits?
✓
X
X
✓
Genotyping method
Whole genome sequencing of embryos or imputation from PGT-A data
Whole genome sequencing of embryos
SNP array
Probably SNP array
Can detect de novo mutations?
Yes*
Yes
No
No
Works with data from any genetic testing company?
Yes
No
No
No
Sequencing of families?
Yes, including extended family for premium product
No
Yes, parents only
Yes, parents only
Long-read sequencing
Yes
No
No
No
*Herasight can only detect de novo mutations if your clinic sends embryo biopsies to their lab. If you use their ImputePGTA product you won't be able to get de novo detection.
Price comparison
Notes on the above graph
Genomic Prediction uses a different genotyping method from Orchid and Herasight, so it has some additional limitations that aren't captured in this price chart. I get into the differences in the section below this.
Orchid Platinum doesn't seem to have a standard pricing yet. I've shown the cost per embryo based on the one report from a person I know who has used it, but it's possible you might be offered a different price by the company. Last I heard it was $10,000 per embryo, with a $7500 discount if the embryo comes back aneuploid.
Herasight Health is Herasight's new "health only" product that is less expensive than their standard $50k product, but doesn't include screening for IQ, height, or ADHD. It starts at $20k, which includes screening for 10 embryos, two of which they'll screen for de novo mutations. If you want to screen additional it's $1500 per embryo, and if you want to screen additional embryos for de novos the price is $2500/embryo (on top of the $1500 base fee).
Herasight also has a standard product but it’s not shown in the chart because it doesn’t vary in price with the number of embryos. The standard price is $50k and it includes everything the company offers (IQ, height, all diseases, expanded carrier screening and universal PGT-M, family sequencing, de novo mutations, polygenic scoring of parents, access to the embryo simulator, updates for the next five years, and a few other things).
What are the actual differences between the embryo selection companies?
There are fairly large differences between the embryo selection companies, only some of which are publicly known. The differences mostly boil down to predictor accuracy, cost, and the set of things which the different companies screen for.
Every capability offered by the different companies is downstream of their ability to read an embryo's genome accurately. And each of the three main companies has a fascinatingly different approach to this problem.
How Genomic Prediction reads a genome
Genomic Prediction uses SNP arrays, an older technology that looks specifically at spots in the genome that commonly differ between people. They measure about 1.7 million locations in the genome to detect which of two variants a given embryo has.
Given the human genome is 6 billion base pairs, you might be surprised that this technique works at all. How is it that we can figure out someone's risk of diabetes or schizophrenia when we're only looking at 0.03% of their genome?
There are two answers to this problem:
First, any given human genome only differs from another along just 0.1-0.5% of its length (0.1% if you only count single base pair changes, 0.5% if you include structural variants such as regions where one person might have an extra copy of a gene).
Second, it's possible to do a decent job inferring the value of genetic variants you don't directly read by making educated guesses about them based on the portion you do observe.
Due to quirks with how sperm and eggs are formed, you can use the measurements of an embryo's genome you do have to guess at the part of it you don't have.
Your ability to make these guesses well hinges on the quality of the reference panel, and since these reference panels are full of mostly European genomes, our ability to guess at the rest of the genome is not as good for non-European individuals.
SNP arrays are also fundamentally limited in their ability to detect rare variants, structural variants, and highly diverse parts of the human genome like the HLA region I mentioned in the story about type 1 diabetes. So there is in fact a reasonably significant tradeoff to using them. The size of this tradeoff has actually grown over time because we've recently gotten a better understanding of the role of rare variants in predicting life outcomes, and Genomic Prediction can't really take advantage of those modern advances. But despite all these limitations, Genomic Prediction can still do an OK job predicting disease risk from a genome.
How Orchid reads a genome
In the early 2020s, Orchid Health became the first competitor to Genomic Prediction in the polygenic embryo screening space, launching a significantly more expensive test whose main differentiating factor was offering whole-genome sequencing of embryos.
Getting a whole genome sequence of an embryo is not a trivial task. To read an embryo's genome, you need to remove 3-5 cells from an embryo around the 5 day mark, at which point the entire embryo is only about 100 cells.
High quality DNA sequencing requires reading the same stretch of DNA 30 or more times. And the DNA is destroyed in the process.
How do you read DNA 30 times when you only have 3 to 5 cells? The cells literally don't have enough DNA for you to read it 30 times.
The answer is that we must first make copies. This step is called amplification. We cut open the cells with enzymes and throw out everything except the DNA. Then we make copies of the DNA until we have enough to work with.
But this process is tricky. The amplification process introduces errors into the sequencing process. Sometimes it amplifies one region of DNA 100 times and another part not at all. Sometimes it makes errors when copying, and copies get copied and you end up thinking there's a mutation in the DNA even though there wasn't.
Orchid (and Herasight for that matter) handle this better than most: they both utilize techniques to reduce these issues with amplification. But it's still not completely perfect, and occasionally Orchid will not be able to resolve a variant because they only read its value a few times. Herasight doesn't suffer from this problem due to their heavy use of long-read sequencing, which I’ll explain in more depth later.
Whole genome sequencing allows us to better predict diseases and traits in embryos because we don't have to guess at the value of variants not captured by SNP arrays. We can directly measure them.
This makes the performance ceiling for whole genome sequencing fundamentally higher than the performance ceiling for SNP arrays. And as our understanding of the role of rare variants in disease risk and trait values has continued to improve, this gap in performance between whole genome sequenced embryos and SNP arrays has grown.
How Herasight reads a genome
Herasight has perhaps the most interesting method to figure out what's in an embryo's genome. Like Orchid, Herasight can do whole genome sequencing in their own lab. But they have an additional, much more convenient method that works on data generated by almost any genetic testing lab, including those who don't offer polygenic embryo screening.
Early in its history, Herasight was working exclusively with embryo data generated by other companies like Orchid and Genomic Prediction. They would take this data, and run an after-market analysis on it, utilizing their stronger, broader set of predictors to better choose embryos with low disease risk, and to screen for things that other companies didn't offer (such as IQ).
However, most parents doing IVF didn't have embryo genomes generated by either of these companies. If they had genetic data at all, it was the more basic type: ultra-low coverage PGT-A data used mainly to detect down syndrome and other chromosomal abnormalities.
If genetic sequencing produced a painting, Orchid would produce a Da Vinci, Genomic Prediction would produce a sketch by a promising young artist, and PGT-A would produce a crayon drawing of a cow.
For many years, these customers were simply out of luck; if you already had frozen embryos, it was impossible to test them again without hurting their chances of becoming a baby.
Sometime in 2024, Michael, the CEO of Herasight, had an interesting idea. Perhaps if he had a high quality genome of the parents, he could use that data to fill in the missing gaps in the embryo genome.
If this could be done, the implications would be enormous. Virtually overnight, hundreds of thousands of parents with frozen, PGT-A tested embryos would suddenly be able to test them for risk of almost every major disease and many of the most impactful traits; everything from diabetes to Alzheimer's to autism to intelligence could be estimated in existing embryos.
Every genetic testing company Michael spoke with about this idea either didn't understand it, or thought it was impossible.
But the company persisted, and in 2025 they managed to get it working. The resulting ImputePGTA algorithm unlocked polygenic testing for hundreds of thousands of couples with frozen embryos in storage.
ImputePGTA is a major breakthrough for parents who already have frozen embryos, but there are also significant benefits for parents who are planning to do IVF soon. These parents no longer have to go to a clinic that works with Genomic Prediction or Orchid (or even Herasight). So long as a clinic does PGT-A and is willing to transfer an embryo chosen by the patient, you can do polygenic embryo screening. This is actually a pretty huge deal, and has opened up PGT-P to customers all over the world.
There’s a special type of sequencing that must be done to make ImputePGTA work, and it’s one that no other polygenic screening company offers; long-read, high depth sequencing of the parents.
Long-read sequencing, especially the high depth kind that Herasight does, is among the most expensive ways to read a genome. The sample preparation method takes days, there are expensive consumables involved. And if you mess up any part of the process you have to do the whole thing over again.
It’s a pain in the ass. But it allows them to do something no other company can do: it allows them to fully phase a parental genome.
Phasing is when you not only read which genetic variants are present in a person's genome, but you identify which of the two chromosomes a given variant is part of. This is extremely important for ImputePGTA because you’re inferring which part of each parental chromosome an embryo got based on crappy PGT-A data. That’s only possible if you know which variants are paired together on the same chromosome in the parent.
But long reads also have some other benefits that aren't widely understood. Some parts of the genome are extremely repetitive for long stretches, and whether or not you get a disease hinges on how many times a given sequence repeats.
If you're reading stretches of DNA 150 bases at a time, you often can't tell how long the repeat is. This is especially important for conditions like Huntington's disease, fragile X syndrome, and spinal muscular atrophy. Herasight is uniquely good at reading these sections of the genome, allowing them to diagnose essentially all codon repeat disorders. This is one of the small ways in which they have an advantage over Orchid specifically when it comes to rare disease.
A full list of such diseases is beyond the scope of this post, but if you have a specific interest in one of these conditions you can just book a call with them and they’ll put you on the phone with someone who can walk you through what’s possible.
Genetic load testing, de novo mutations, and other differences between embryo screening companies
Every new generation of children receives ~100 new genetic mutations that their parents didn’t have. These genetic anomalies are referred to as “de novo” mutations, because they aren’t really transmitted to the child via typical inheritance. Instead, they come from a DNA copying error or (less commonly) from a cosmic ray hitting your dad in his balls.
Most of these mutations will have approximately no effect. Usually they only change a single letter in a part of the genome that isn’t directly translated into a protein, thus the effect will be small or zero.
But not always. Every now and then one of these mutations will hit a protein coding region and change the sequence of amino acids. And sometimes these mutations will occur in very, very important genes.
This still doesn’t necessarily cause problems. Sometimes you'll get lucky and the mutation will be silent, meaning the protein won't be changed.
But sometimes you don't get lucky, and the results can be catastrophic.
Among these very important genes are a set of proteins called "highly conserved sequences". They’re called that because they're virtually identical across most if not all humans, and if their biological function is fundamental enough, most mammals. Sometimes they're even identical across whole branches of the tree of life.
Mutations in these genes can lead to anything from a mild physical or mental impairment to a developmental disorder so catastrophically bad it literally ends a pregnancy before birth. And it can lead to anything in between.
Fortunately for the human species, these kinds of mutations are rare. Our best guess is only about 0.34% of children will be born with such a mutation. The rate is significantly affected by parental age, especially the age of the father, who is the dominant source of these mutations.
Reducing the chance of these sorts of issues (along with remaining more fertile for longer) is one of the strongest arguments for freezing your sperm. If you freeze your sperm around age 20 (or better yet sometime in your teens), you can cut the number of de novo mutations your children get by a third or more.
Orchid was the first company to offer screening of de novo mutations several years ago. Herasight followed suit recently, though it should be noted that this is not available if you use their ImputePGTA product (they need to be able to sequence the embryos themselves to call de novos).
I am probably somewhat biased here, but I think Herasight’s tech to classify the pathogenicity of de novo mutations is probably the best currently on the market. They recently released a predictor called “NeuroRisk” which to the best of my knowledge is better than any other predictor to date at identifying mutations that cause severe developmental disorders, including non-verbal autism.
Family history
Herasight has some very neat tech that takes your family history into account when predicting your embryo's risk of a disease. They can look at family members who have been diagnosed with the condition and figure out how much DNA they have in common with each embryo. This allows them to estimate disease risk even when they don't know which DNA changes are causing the change. So far as I know, they're the only ones doing this.
Herasight also takes family history into account when estimating the baseline risk that one of your embryos gets a disease. When I last checked about a month prior to this post, Orchid wasn't doing this. In practical terms, this means Orchid is more likely to underestimate an embryo's risk of a disease for which you have a family history.
Expanded carrier screening and universal PGT-M
About 15% of couples are carriers for a high impact single gene variant. Conventional genetic testing basically never catches this stuff unless you already know you're a carrier and order a test specifically for a known issue.
For the rest of us, it's a crapshoot. You conceive naturally or via IVF, and if you or your spouse are in the 15% that carry one of these things, each of your kids will have a 50% chance of getting it from you.
These mutations vary in their significance; sometimes they're relatively benign (you'll have a significantly increased risk of some condition in old age), and sometimes they're very, very scary (sudden death from heart failure in your 40s, dramatically increased risk of non-verbal autism). A few of these are well known and well understood; the gene that causes Huntington's disease, for example, has been understood for decades.
Most of these are dominant variants, meaning they’ll actually manifest in the parents. This can actually be a life-changing diagnosis: Herasight has, in more than one case, identified a pathogenic variant that causes massively increased risk of sudden heart attack in their customers. In several cases, the conditions whose risk was increased by these variants had preventative treatments that could substantially reduce risk.
Without a test like this, it's very common for neither of the parents to know there's a potential issue until they get sick. And even when they do become symptomatic, the doctors don't always identify the issue correctly. And even when they do, undoing the damage can be difficult or impossible.
We've been able to test for some of these variants for decades, but only if the IVF clinic knew to look for it (which usually meant a known family history for a specific condition and confirmation that one of the parents was either a carrier or affected).
The lack of universal screening for high impact monogenic variants is one of the most tragic failures of modern IVF. Extrapolating from 2019 data and the recent growth rates of IVF, there were probably around 200 children born per day with a serious genetic variant that likely could have been avoided.
This article is mainly about polygenic embryo screening and all the amazing things you can do with it, but if you’ve got one of these high impact monogenic variants, that all goes out the window until you’re certain your child will not carry it.
For all their importance, we know shockingly little about these variants. I wish I could show you a graph of the distribution of the impact of these sorts of things, but we're just now starting to understand this stuff. I don’t want to brag too much here (and I can’t, since I didn’t really do any of the work to make this happen), but Herasight probably has the best tech for screening these kinds of variants at the moment. If anyone is interested in learning more about this, reach out to me via email or better yet just book a call with us using our contact form.
Orchid also screens for this kind of stuff, but I believe at the moment their panel (at least for the main product) is more limited than the one offered by Herasight. Orchid Platinum offers screening for a broader set of genetic variants, but from what I’ve heard it can be very, very expensive ($10,000 per embryo last I heard).
What’s the deal with Nucleus?
You might have noticed I’ve been avoiding mentioning a certain company up until now: Nucleus Genomics, probably the most well-known company currently offering polygenic embryo screening.
The reason for this is actually pretty straightforward; Nucleus has almost certainly been misleading customers about how good their genetic predictors work since they were founded in 2021. The CEO has, as one might expect, denied all of these allegations. But it would be pretty straightforward for them to release convincing evidence that their predictors actually work, and they haven’t done it.
To give a simple example, here’s a graph showing the performance of Nucleus’s genetic predictors implied by their reports vs the actual performance when their predictors are assessed:
The fact that the red bars are lower than the blue bars for all but one condition (schizophrenia) indicates that Nucleus is systematically misrepresenting how well they can predict genetic risk in their customers.
This is obviously a major problem. If your company’s entire value proposition is that you can predict an adult or embryo’s risk of a disease, but you report is miscalibrated on almost every single condition, that’s really bad!
Nucleus has taken SOME steps to improve things since they launched their embryo screening product. They released the Nucleus Origin white paper, the company’s first actual validation of their genetic predictors. The paper does within-family validation of genetic predictors for several diseases, it produces strong results, and it even quantifies the general level of drop-off in performance for non-European ancestry groups (though it doesn’t give a condition-by-condition performance comparison for these groups).
But there are still problems. For one thing, they’re not just offering embryo screening for the diseases validated in their white paper. If you go to their website, you’ll see they offer screening for tons of things. And it would not at all be surprising to me to hear that those predictors probably suffer from the same miscalibration as the ones they were using previously.
Second, Nucleus appears to still not have rolled out their updated predictors for adult testing, meaning they’re still using the crappy low quality predictors on paying customers even after publishing the Origin white paper. It has been five months since its publication. I don’t understand how they have moved this slowly.
Maybe at some point Nucleus will fix their problems and offer a good product. But despite having raised $32 million, the CEO has so far proven either uninterested or incapable of doing so. I’m not holding my breath for that to change.
How do I do this? Where do I start?
If you want to do polygenic embryo screening, and you’re in a position where you can handle the financial and physical costs, the best place to start is probably by scheduling a consultation with one of the polygenic embryo screening companies.
Get in contact with Herasight here
Get in contact with Orchid here
Get in contact with Genomic Prediction here
Any one of those companies can give you a basic overview of the process and tell you which clinics you can work with to do polygenic embryo screening, or how to ask a clinic to send biopsies to their lab.
To answer the all-important question of “will this clinic transfer an arbitrary embryo of my choosing”, you’ll usually have to book a paid consultation which typically runs between $250 and $500 in the US. If you get answers for a specific clinic, please let the rest of the world know the results! I’d like to put together a list of different clinics that support PGT-P, including info about which PGT providers they’ll work with. Any info you can provide to the rest of that helps support other people going through embryo screening.
Once you’ve found a clinic you want to use that will let you transfer an embryo of your choosing, and you’ve gone through the first consultation, you’ll begin the testing process.
One of the very first things a clinic will do is take a blood test and do an ultrasound. Two of the most important measurements they’ll take here are your AMH and your AFC. Both of these measurements can give you a rough idea of how well egg or embryo freezing is likely to go for you. And generally speaking, higher is better.
Assuming all looks good, you’ll start hormone injections to prepare for egg retrieval usually within a month or two of the initial consultation. After 10-12 days of injections, ultrasounds, and blood tests, you’ll travel to the clinic to get your trigger shot. This shot usually contains a mixture of lutenizing hormone (LH) and human chorionic gonadotropin (hCG), and allows the egg to be released from the ovarian follicle in which it’s contained.
About 36 hours later, you’ll return to the clinic for the actual retrieval, during which a doctor will retrieve eggs from your ovaries under the guidance of ultrasound. They’ll usually use local anesthetic for this procedure, meaning you’ll usually be able to return to your work or normal life within a day of the procedure.
There’s a surprising amount of variance in the side effects people experience from egg or embryo freezing. One woman I know had basically zero symptoms from multiple rounds of egg retrieval. Another found herself doubled over on the bathroom floor in pain during one particularly bad retrieval.
Most women experience something in the middle: mild bloating and abdominal discomfort along with some degree of mood swings. This usually is on the level of “bad period”.
The two worst side-effects of egg retrieval are internal bleeding and ovarian hyperstimulation syndrome. Internal bleeding of the type that requires medical intervention is pretty rare; less than 0.1% of cycles. Ovarian hyperstimulation syndrome is more of a continuum, with mild bloating on one end and hospitalization on the other. Hospitalization from egg retrieval is fairly rare; about 1%. There are also strategies for preventing the more severe forms of OHSS, such as taking letrozole during stimulation if your e2 levels get too high, and taking cabergoline after retrieval to reduce bloating.
You’ll likely want to do 2-4 rounds of retrievals to create all the embryos, with the exact number varying fairly substantially depending on how well you respond to stimulation and how many children you want. I’ve had friends do one retrieval and I’ve had friends do ten.
How to get cheap IVF medication
IVF medication usually runs between $4500 and $6500 per round. If this sounds expensive, that’s because it is. It usually makes up 20-30% of the cost of IVF. But it’s an area where an enterprising woman can significantly bring down costs.
Believe it or not, one of the best places to currently get major discounts on fertility medications is TrumpRX. The website launched in early February of 2026, and as of this writing, it has significant discounts on several major IVF medications like Gonal-F, Cetrotide, and Ovidrel.
GoodRX also often has discounts on drugs like Ganirelix, Leuprolide, and Endometrin.
Specialty pharmacies often have very good deals on particular medications. IVFPharmacy.com has very good pricing on Follostim. According to some old forum posts, Mdrusa.com apparently had very competitive pricing on Menopur. If you want to check their current prices you'll need a prescription.
If you put all these together, you can just about halve the price of IVF medications.
There's one last source of cheap meds I haven't mentioned yet. It's cheaper than all the rest, sometimes by a factor of 20: Peptide chat.
Peptide chat is a gray market supplier of “research chemicals” including the “Chinese peptides” everyone has been going crazy for lately. One customer I know bought Menopur from them for 95% below the listing price on the cheapest conventional pharmacy. She had several IVF cycles with stupidly good results while taking these meds (though this is very likely just a result of her unusual biology rather than because the medications they supply are extra special). She got Menopur from Semag Peptide (it’s labeled HMG and sells for $70 per 750 IU).
I know a few people who have used Peptide chat for various medications, so I know at the very least that they’re not usually lethal or a scam. But this is still very much a "use at your own risk" type of medication supplier, so don't take this as an endorsement of them from me. It's simply a possible source of medication you may want to look into more.
All together, medications will run between $300 at the very low end and $6500 at the very upper end. $2000 or so is about the lower limit for traditional sources of medication. If you want to go lower than that you’ll need to get meds from the gray market peptide dealers or from women selling their leftover meds on Facebook.
Connecting with me and others in this process
If you’ve got questions about IVF, feel free to either leave a comment or send me an email at genesmithlesswrong@gmail.com. I know quite a few women doing egg freezing or IVF who are interested in polygenic embryo screening, so if you’d like to connect with others going through a similar experience, let me know and I may be able to add you to some group chats.
If you’re in the bay area and would like to meet up in person, feel free to drop me an email. I’m always happy to chat with people who are serious about doing polygenic embryo screening, or who are interested in working in the field.
FAQ
Is this post medical advice?
No
Are IVF babies less healthy than naturally conceived babies?
The short answer is probably not, it's hard to rule out entirely because there are no proper randomized control trials. There are many studies showing the average child born via IVF has more problems, but almost every single one I've looked at is confounded in some pretty obvious way.
Historically, parents who use IVF are older. They're sicker. They often suffer from repeated miscarriage or have uterine issues which can lead to premature birth. And the (increasingly uncommon) practice of transferring multiple embryos at a time led to high rates of twin pregnancies from IVF, which themselves are known to carry additional risks for the babies and the mother.
I’ve looked at about half a dozen studies on this topic, and essentially all of the ones that find harm don’t properly control for these kinds of selection effects.
There’s one exception, which is a Nordic study showing a higher rate of childhood cancer when using frozen embryos rather than fresh. I couldn't fully explain this effect with selection effects, though there may be something I'm missing.
The absolute risk increase was very small; I believe around 0.2%. And there are some other reasons why this result might not replicate in a modern setting: the freezing protocols used in most of these cycles were the old, slow freezing methods rather than modern vitrification techniques to freeze the embryos.
Still, this is the one result I've looked at where the authors seem to have done a decent job adjusting for confounders, and they still found this a negative effect. So although there's not much evidence that IVF itself is bad, we can't rule out negative effects completely.
This whole topic deserves further elaboration, but I’ll have to save that for another post.
How do we know embryo selection actually works?
More skeptical readers might wonder how we know embryo selection actually works. How can we actually validate that these genetic predictors work if the first polygenically screened baby was only born in 2019?
The answer is we test the predictors in existing people. So we get a bunch of old people from UK Biobank or some other source of data, make predictions about which of them have cancer, then check to see how well we did.
"But", you might contend, "you're just seeing that the genes you've identified are correlated with disease. How can we be certain they're actually causing that observed increase?"
This is a very good question, and in most fields we wouldn't be able to go any further than this. Except in genetics, we actually can test whether they're causal. To do this, we test our predictor in siblings.
Siblings have this amazing property, which is that they inherit a randomized subset of DNA from each of their parents. Importantly, the subset they get is not affected by the subset their sibling got. So if we test a diabetes predictor and we can predict which sibling has diabetes better than random chance, we can be sure that we truly are picking up a causal signal.
This is why sibling validation is so important, and why you should generally trust companies that have extensive sibling validation more than ones that don’t.
If I want to use a cheaper clinic, do I need to spend 3 weeks traveling?
No. Most clinics (especially ones that see many travelers) offer something called “remote monitoring” which allows you to do the required ultrasounds and blood tests at a facility close to your home, and only come to their clinic for the last 3 days or so of your retrieval. This is something worth asking about during your consultation.
Which clinics definitely offer polygenic embryo screening?
Every polygenic embryo screening company has their own list of clinics they work with, but they're cagey about sharing it publicly. So unfortunately if you want to figure out whether a nearby clinic will work with them (specifically by sending embryo biopsies to their lab), you'll have to either call the clinic or the screening company directly. Generally speaking it's better to contact the screening company, since not everyone at the clinic will know which PGT labs they work with.
Which clinics definitely DON'T offer polygenic embryo screening?
Spring Fertility in San Francisco once fired a friend of mine as a patient after she mentioned she wanted to do polygenic embryo screening. I would strongly recommend not using them for this process.
How many rounds of IVF should I do?
Generally speaking, you want at least 2x as many euploid embryos as you want children. Any fewer than this and you’re not going to get much of a benefit from polygenic embryo screening.
What should I do with my immature eggs?
Freeze them. Most clinics will throw them out. But there’s good technology to mature between 40 and 70% of your immature eggs and it’s worth using!
In most IVF cycles, about 10-30% of the eggs harvested will be immature. Normally these just get thrown out. Sometimes if a patient is really desperate, or if they’re doing a special protocol called “low-stim”, the clinic will save these eggs and try to mature them with some special liquids.
This doesn’t usually work that well. Traditional IVM liquids can only turn about 40% of immature eggs into mature ones. Even when they succeed, the resulting eggs develop into implantable embryos at a lower rate.
A year ago a company called Gameto announced that they had a new way to turn immature eggs into implantable embryos at about twice the rate that was possible with previous techniques. In May of 2025 they announced the birth of the first baby created from an egg that was matured using Fertilo, as part of a clinical trial.
As of this writing, Fertilo is available in Mexico, Peru, and Australia. It likely won’t be available in the US until 2027, at which point you’ll be able to get it prescribed off-label by your doctor. If you save up immature eggs from multiple cycles, there will likely be a way to dump all those immature eggs into a Fertilo bath and mature about 70% of them.
This will probably boost the number of eggs you get per cycle by 10-20%. It’s not a huge difference, but clinics don’t tend to charge you more for freezing immature eggs, so you might as well do it.
Should I save some eggs or should I just make embryos?
I think there’s a reasonable chance we can get embryo editing or sperm screening working in the next five years. Embryo editing would allow you to get rid of genes like APOE e4 for alzheimer’s or some BRCA breast cancer variants, or some rare diseases, but it will only work on freshly fertilized eggs. If you’ve already got frozen embryos you probably won’t be able to utilize editing tech.
Sperm selection will involve selecting the best sperm and fertilizing an egg with it. This tech is obviously still speculative (no one has gotten anything working at the moment, but if it did work it could potentially double the expected gain from embryo selection). You won’t be able to use sperm selection if the eggs have already been fertilized.
For this reason it may be worth freezing some number of extra eggs just in case one or both of these technologies come online.
Can I do embryo screening outside the US?
Yes, you can do embryo screening outside the US. I know several couples that have done it in Europe, and a few elsewhere, such as Dubai.
There are some countries where it’s actually just impossible: Germany being perhaps the most notable. The UK HFEA has also published guidance stating that polygenic embryo screening is illegal, though it’s not entirely clear whether they really have the statutory authority to do so. Australia is similarly prohibitive of this tech at the moment.
Polygenic embryo screening is feasible in most of the rest of Europe, though the degree of feasibility varies a bit by country.
Which supplements should I take?
It's probably worth talking with your doctor about CoQ10 and NAD+. A lot of the other stuff doesn’t have much evidence behind it, though I’m increasingly thinking that Rapamycin has potential for women that have high aneuploidy rates.
Are there any PGT labs I should definitely avoid?
If you’re going to use Herasight’s ImputePGTA to get polygenic scores using regular old PGT-A data, there’s one particular PGT-A lab you should avoid using: Juno Genetics.
Juno not only has the lowest coverage depth of any PGT-A company (meaning imputation is less accurate), but they have a history of refusing data requests by customers and violating HIPAA rules around this. This will likely change at some point in the future (the law is actually pretty clear that Juno needs to provide raw data to customers, and they definitely are violating HIPAA with their current actions). But this may take some time to work its way through the legal system.
In the meantime, avoid using Juno at all costs.
How did you make the gain calculator?
I combined Herasight's IVF calculator with their gain calculator and pulled numbers on predictor quality from Genomic Prediction and Orchid from their most recently released paper (hat tip to Spencer Moore and the rest of the team for these numbers). I also used some unreleased numbers from Herasight.
In all cases, I've tried to get the most up-to-date numbers I could for all companies. In the case of Genomic Prediction, this process was very frustrating. The company claims to have better predictors than the ones shown in their published paper, but after several back-and-forth discussions with them, they decided it wasn't worth their time to even tell me the predictor performance, let alone validate it.
So I've defaulted to using the latest available numbers from their publications. Maybe they have better numbers internally, but they don't seem to consider it a high priority to communicate this to customers.
Will I get the same gain from embryo selection if I'm already smart, or already tall?
Basically yes. Counter-intuitively, your starting point for any continuous trait is almost irrelevant to the expected gain. Explaining exactly why that happens is perhaps beyond the scope of this last minute revision at 11:30 PM, but it's related to the number of genetic variants involved in the trait. Even very smart or very tall people only have a few hundred more "tall" or "smart" variants when compared to the average person. But there are over ten thousand such variants, so there's headroom in both directions.
The same can be said for almost any continuous trait.
Note, there is in fact reversion to the mean for these complex traits, so while you'll still see the same gain relative to an average child, you won't see the same gain relative to the parents; if the parents are super smart, even a screened embryo may be less smart than them in expectation (ditto for other continuous traits)
Mean reversion is a whole can of worms, but the mean you're reverting to is basically the mean of your grandparents, great-grandparents etc. If by some miracle everyone in your family tree going back a few generations was as great as you, then your children wouldn't see any mean reversion.
What else will I be able to select for in the future?
At some point in the next year or so it will likely be possible to nudge personality traits like extraversion and neuroticism, though the predictors for these traits are going to take another few years to catch up with predictors for disease and intelligence. You’ll also likely be able to select against severe depression risk later in 2026.
These sorts of traits are pretty interesting for singularity-pilled people because they are the sort of thing that could continue to have significance, even if artificial superintelligence is right around the corner.
We don’t yet have good predictors for athletic performance, or physical appearance beyond height and eye/hair color. More abstract but important traits like “courage”, “charisma” and “tendency to behave pro-socially” are also at least a few years off.