Revisiting The Seven Trends That Define The Future Of IVF

Pre-ASRM prep notes, part 2.

Back in 2015 I wrote a piece for Forbes that made a bunch of predictions about where IVF was heading. Time to re-examine. (The original article is online: [https://www.forbes.com/sites/davidsable/2015/02/28/the-seven-trends-that-define-the-future-of-ivf/?sh=5c2a12cf494b])

Then:
Prediction 1. IVF for the prevention of disease: The combination of 1) inexpensive human genome sequencing, 2) a vast increase in the number of known identifiable genetic diseases and 3) the wide availability of cheap 23andMe type genetic screening will result in an explosion of demand for IVF from fertile couples who wish to prevent the transmission of genetic diseases to their children. This trend, which started in the 1990’s, will more than double the demand for IVF worldwide.

Now:
That made a lot of sense, but sadly it’s not happening. The percentage of IVF cycles performed to prevent monogenic disease is still tiny, even as billions of dollars are being spent on research and development for gene therapies and gene modification therapeutics to treat the diseases that we can easily (and relatively cheaply) prevent with IVF and PGT-M. Meanwhile polygenic screening (PGS) of embryos for infertility patients undergoing IVF, a pool unenriched for disease disposition and therefore likely to yield very high false positive results, is being introduced into the marketplace. PGS holds some promise once the quality of the outcome predictions increases, but its value pales in comparison to the benefits of taking a monogenic disease risk from 25% or 50% to zero.

We should do better.

Then:
Prediction 2. Much greater cost pressure on the IVF procedure. Competitive cost pressure has already moderated the rise in IVF pricing, but more widespread IVF coverage will accelerate this trend, as patients expect the same limits on out-of-pocket expenditure as they see with other medically-necessary procedures.

Now:
We’re getting there. Employer based coverage is accelerating rapidly, and cycle discounting to larger purchasers is gaining some traction. Larger, consolidated providers are using predictive analytics to solve for dollars to baby and time to baby, outcome metrics much more in line with patients’ desired outcomes. Macro market forces move slowly, but I expect these trends to continue.

Then:
Prediction 3. Standardization of procedures, including increased automation. Note the graph showing Moore’s Law (drop in computing costs) and the extremely rapid drop in genome sequencing costs. Why have IVF laboratory costs stayed relatively constant (actually increased) since IVF was introduced decades ago while the no-less-complex sequencing costs plummeted in a much shorter time frame? We will examine the reasons in a future column, but market dynamics will inevitably reverse the increase in the costs of performing an IVF cycle.

Now:
A lot of work (and capital) is being put to work on this, particularly in cry-storage and biobanking, and certain robotic aspects of embryology. As we say in the early stage VC community, tinkerers will continue to tinker, and engineering risk is more manageable than basic science risk, so expect methodical progress in this area.

Then:
Prediction 4. IVF Mega-Clinics. I have seen countless business plans over the past couple of years describing various combinations of IVF centers in different parts of the country merging, gaining economies of scale, trying to maintain pricing power and protecting quality branding. This trend will accelerate as the market expands and consumer decisions are made less by individual patients and more by a combination of large insurers assembling networks and Uber/Open Table/Zoc Doc aggregators efficiently helping patients find an appropriate clinic. As has occurred in many areas of medicine, business will move to big purchaser (insurer/payor/patient purchasing service) buying from big provider (hospital/mega clinic.)_

Now:
Yup, ongoing. Private equity funded, catalyzed by senior operator-founders looking for exits or diversification and in response to unmet demand and increased insurance coverage, the IVF demand curve is shifting, and that shift is being driven by larger, more process-oriented programs. The “mega” in mega-clinic is more likely to be a multi-site, multi-state chain of sorts than a 100,000 cycle Infertility Mall of America, but 40,000 cycle facilities seen in Asia are likely a glimpse into the US IVF market’s future as well.

Then:
Prediction 5: A quantum leap in IVF technology. IVF was 1980’s technology and cured many cases of anatomic and unexplained infertility. Intracytoplasmic sperm injection (ICSI) and pre-implantation genetic diagnosis (PGD) were 1990’s technologies aimed at male factor and genetic-related infertility. The years since have seen incremental improvements in IVF techniques, but nothing revolutionary. _

Now:
Maybe not quantum, but certainly steps, most in the right direction. Science is hard, oocytes are slow to reveal their development secrets, and sperm remain mute — we haven’t figured out how to talk to sperm yet (some excellent basic science work by Ohana Biosciences ((disc: I was a board member)) unfortunately remains a science project for now.) The field of women’s health in general, and ART in particular, is desperately in need of new molecular targets for therapeutics, and our pathways need to be fleshed out in a fashion similar to those in immunology, oncology and inflammation.

Then:
Prediction 6:Widespread IVF medical tourism.

Now:
Well, yes and no. Cross-border treatment is the norm in Europe, often driven by “regulatory arbitrage” as patients in permissive countries like Spain as often as not come from countries that are more extensively regulated, like France, Germany and Italy. The years since my 2015 article saw large increases in patients from China seeking treatment elsewhere in Asia (Singapore, Malaysia, Thailand, and Australia for example) as well as in the United States and Canada.

Then came Covid. And all bets were off.

Maybe not so much. If the rapid rebounds we observed in domestic IVF cycle volumes is an indication, as travel restrictions and hesitancy disappears, cross border IVF volume growth will likely resume at a similar (or possibly greater) pace.

Then:
Prediction 7: New treatments described above and others aimed at what we call “the egg factor,” one of the most vexing challenges in reproductive medicine, will result in the gradual disappearance of egg donation as a treatment for infertility.

Now: Not so much. There has been an encouraging re-emergence in in vitro maturation (IVM), and some brilliant early basic science work on stem cell use for de novo oocyte creation, but if anything threatens the use of egg donation, it may be the maturation of the large pool of proactively retrieved, vitrified and stored eggs, and those are unlikely to tapped into in large number until later this decade.

Overall — many of the 2015 predictions seem pretty rational and logical now. We are making headway on most of them, and IVF patients in the near and distant future will benefit from these areas of progress.

In the meantime we humbly charge ahead, knowing that the greatest advances are likely those that we’re not imaginative or creative enough to predict. Yet.