Thread by Will

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1/ In early 2022, I began a ~9 month project to write: "what's up with fertility?", ranging from demography to assisted reproductive technology.

Of course, the "tale grew in the telling", so 40k words later I covered many more Qs that came up...
2/ An early question: is infertility actually on the rise?
3/ How common is infertility? This was a tricky one to answer, because "it depends" comes up an awful lot.
4/ How much does IVF boost total-fertility rates? It depends a lot on how quickly it is initiated.
5/ Switching gears to developmental bio, how close are researchers to achieving human in-vitro-gametogenesis (IVG) = making eggs/sperm from somatic cells? Let's start with gametogenesis 101:
6/ Okay, and what's the SOTA of IVG in animals? An important caveat: this field is moving pretty fast, & since there are multiple private companies working on this problem, my paper is probably low-balling progress here.
7/ There are lots of interesting challenges awaiting succesful deployement of IVG. Scientific challenges include 1) transferring some of the IVG approaches to humans; 2) preventing epigenetic/imprinting defects in offspring; 3) somatic mutations 4) many more
8/ Key regulatory Q's: 1) would IVG-derived embryos = genetically engineered embryos, which FDA is currently barred from considering? 2) if they don't count, what safety data would the FDA require before allowing trials in humans to proceed? related: www.statnews.com/2022/04/22/congress-allow-mitochondrial-replacement-more-forward/
9/ Synthetic embryos make the headlines, but an underrated fertility challenge is (pardon the pun) the Reproducibility Crisis: many in-vitro fertilization (IVF) add-ons have poor evidence for efficacy. Leaned on @jd_wilko work a lot for this section.
10/ Also underrated: IVF has been used for the prevention of monogenic (single-gene) disorders for 20+ years through Preimplantation Genetic Testing for Monogenic Disorders (PGT-M). How? 1) generate several embryos 2) screen them for specific mutations, 3) implant non-carriers.
11/ What about sorting sperm? Sperm are plentiful and have traits we can measure relatively easily & at scale: motility 🏃💨, charge ⚡, and morphology 📏. If those characteristics correlated with clinical outcomes, that would be amazing! Unfortunately, evidence is poor...
12/ I cover these topics, and much more (embryo selection with polygenic scores, reproductive aging...) in the whitepaper. Highly recommend using ctrl+f to find the sections you're interested and shoot me a DM if you want to chat!
Link: docs.google.com/document/d/e/2PACX-1vT1hgf95phUa4e1nqf2VTfjFmUeSBwb7mihE86cU6bE1EI-EZteWm6UmeC18PJSs3...
13/ Thanks to everyone who helped out ❤️
14/ I have a list of potentially fundable projects at the end. Check them out!
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