When Is An IVF Add-On Good Medicine?

Practicing Anti-Exploitative Healthcare

The debate about IVF add-ons, additional procedures of variably defined efficacy, backed up by lots of or little bits of or essentially no convincing or unconvincing data, that are sold to patients in the hopes of improving the probability of a good cycle outcome, is not as loud in the US as it is in Europe, but it always comes up in founder-investor meetings. The debate usually includes:

a) Add-on opponent: IVF is expensive enough as it is

b) Add-on proponent: we need to address non-embryo development factors, particularly implantation and our (fill in the additional test) does that

c) Opponent: the claims seem exaggerated and are based on small studies with unrepresentative inclusion criteria

d) Proponent: the same could have been said for IVF in the 1980s, and ICSI in the 1990s and has been said about PGD/PGT since it was invented.

e) Opponent: nonsense. You were able to measure IVF outcomes in tubal factor patients from the start; ICSI outcomes were isolated using fertilization rates, and PGD/PGT had convincing data in well-defined subpopulations from the start (translocation patients, >3 cycle failures using cell-stage biopsy and analysis in >35 yo women.) Most of the procedures being added on now supposedly affect pregnancy rate, and because of cycle-to-cycle variability and confounders the studies would have to be much much larger than those being done to isolate the effect of the extra intervention (and the value of the extra cost).

Having engaged in these discussions since the first Clinton administration, I look at it more as a marketing issue rather than a healthcare issue, one that reflects the decentralization of IVF care from everything under one roof performed by one organization model to a general contractor with a subcontractor model.

Back in the 1990s, I was fortunate (“blessed” is a more accurate description) to have Dr. Jacques Cohen’s “Bell Labs of Embryology” as part of our IVF program at Saint Barnabas in New Jersey, and Jacques and his team had an ever-replenished pipeline of ideas that were vetted as part of our practice. Some were minor variations of technique that the embryology team tested informally and gradually adopted or rejected; others were more major departures from standard operating procedure requiring informed consent and institutional review board review — these innovations were ultimately presented and published and sometimes adopted by others.

Back then the economic benefits came from better pregnancy rates which attracted more patients — unless the procedures, once adopted, cost a lot to perform, the way ICSI and PGD/PGT required expensive micro manipulators attached to operating microscopes and an advanced level of training for the embryologists performing the procedures.

This model changed when the individual procedures moved out-of-house; the PGD subcontractor (disc: Reprogenetics eg, of which I was a co-founder in 2000) provided blastomere or trophoblast analysis to the general contractor IVF program — for a fee, which was, in turn, passed along to the patient.

In the past 20 years, many different tests and services have been offered on this basis; a model where instead of utilizing whatever in-house tools the program had at hand to give the specific patient the best possible chance of conceiving, all for the same bundled fee, the general contractor IVF program performed their in-house basic IVF cycle, added in extra tests and added the subcontractor’s test fee to the total.

Now no one wants their IVF program to be like a car showroom, where your Camry can come with the luxury package or the sporting package or what have you, or — worse — you have to choose whether to upgrade your steering without knowing a rack-and-pinion from an anti-lock brake. You just want a safe, comfortable, and reliable car.

In a perfect world the expected benefits of extra input X, whether it is a satellite radio or an endometrial scratch, should be evident and obvious to whomever is making the purchasing decision. In the imperfect world of IVF decision-making, where the knowledge difference between the patient and the doctor or clinic is enormous, the discretionary aspect of asking the patient whether or not to do the extra procedure or the added technique seems counter-productive; asking that same patient to pay extra, sometimes many hundreds of dollars extra, is somewhere between aggressive and exploitative.

If there is evidence that a procedure improves outcomes and that that improvement can be quantified, then the value proposition can be readily identified and priced in a 10% higher probability for an IVF cycle with a $10,000 base price suggests a reasonable range for pricing; you can make the argument (and I have made these arguments, back in the day) that every applicable cycle should include the technique and everyone should pay something less than 10% of $10,000 for it — resulting in an aggregate increase in the number of good outcomes and avoiding failing to help someone for whom the procedure had a demonstrable benefit, even though the added benefit did not guarantee a positive outcome.

In the absence of reasonable arithmetic certainty of the marginal benefit, the costs of the additional procedure should be allocated to the third-party “add-on” company, the IVF clinic, and the patient, with the overwhelming burden of the risk of uncertainty allocated away from the patient — she is least capable of assessing the potential benefits, and the only one of the three parties to the decision who won’t benefit in any way if the procedure never proves its worth.

The add-on company benefits from whatever revenue it accrues and from the data the outcomes generate, as does the clinic, which may use the data from one patient’s unsuccessful cycle to refine its practices regarding using the extra procedure in the future.

Looked at from a different angle, the “add-on” controversy is part of IVF’s “retail medicine” model, ie an individual patient purchases a cycle and pays the bill, either with no negotiating or with discretion over adding or omitting incremental costs with no ability to assess the value proposition, if any.

This is where our industry needs to be careful. There is a big difference between: 1) Do you want to pay an additional two thousand dollars for a polygenic risk assessment of your embryos? And 2) How about another $1000 for filling your tires with nitrogen or advanced-grade rustproofing of the undercarriage?

Information about rust-proofing is readily available and the stakes of a wrong decision are relatively trivial. For new IVF techniques, the information asymmetry is much greater, as are the stakes, and patients, understandingly wary of avoiding a lifetime of regret, are extremely susceptible to “let’s do everything possible” type arguments.

In the near term, this will play out clinic by clinic, cycle by cycle. Longer term, however, as the retail model morphs into more of a large purchaser—large provider model facilitated by greater insurance coverage and clinic consolidation plus better data collection, some version of a more efficient pricing structure will emerge, hopefully rewarding clinically relevant innovation with compelling (and aggressively collected and presented) data.