Entrepreneurship in IVF: An Overview

The Columbia Business School Alumni Association packed a midtown conference room last week to discuss the Business of Reproductive Medicine. I had the privilege of moderating a panel that included RMA of NY founder and reproductive endocrinologist Alan Copperman, Prelude Fertility CEO Susan Hertzberg, Union Square Ventures’ Rebecca Kaden, Anne Morriss, CEO of Genepeeks and reproductive endocrinologist Mylene Yao, CEO of Univfy.

We have all sat through (and on) tedious industry panels where the participants look at each other after every question, each hoping someone else will think of something novel to say and speak up. This panel was the opposite, thanks to the knowledgeable and candid speakers, and some really insightful questions from the audience. I highlight the key points below.

Reproductive Medicine Industry Snapshot

There are 75 million women in the United States between the ages of 15 and 50, and 6 million pregnancies per year total, resulting in 4 million live births.

The U.S. has 34,000 ob/gyn’s, approximately 1,000 of which are subspecialty trained in reproductive endocrinology (called RE’s), with 34 newly trained RE fellows graduating per year.

There are between 450–500 IVF programs in the U.S., performing slightly more than 200,000 IVF cycles per year, producing 65,000 babies, or approximately 1½% of U.S. births.

The use of IVF in the U.S. lags other developed economies. In Australia, for example, IVF accounts for 4% of births per year. Use of the procedure correlates with out of pocket costs to the patient in each country.

Treating infertility, with a prevalence of 7 million people, is a $4–5 billion business in the United States. For comparison, (obviously very different types of medical conditions), the prevalence of cancer in the United States is approximately 15 million, and spending on oncology is over 85 billion dollars.

Trends in the industry include the consolidation of IVF programs into large mega-clinics, often funded by private equity, the emergence of elective egg freezing for proactive management of age-related infertility, and the expansion of the use of IVF for the prevention of genetic disease, mirroring an expansion of pre-conceptual genetic screening as part of family planning. IVF is still largely self pay. Insurance coverage is mandated in a number of states, although the nature of the mandates differs greatly from one state to another. A number of large companies are creating their own plans and providing coverage to their employees, particularly companies with high costs of employee recruitment and retention.

The Problem Of Access

We’re nowhere near the ideal of a 100% live birth rate per cycle, but the consolidation of care into large programs, usually (but not always) accompanied by adoption of tested standards and constantly improving processes, means that those undergoing IVF now receive very good care from well-staffed programs with well-run laboratories.

Unfortunately, the industry only accommodates a small fraction of the population in need. A relatively fixed number of practitioners and facilities provides incentives to improve the quality of service but not to expand or to migrate to another point on the industry demand curve. Not all of the 7 million women with infertility need IVF, but utilization in other countries strongly suggests that hundreds of thousands of patients have limited access to, or simply cannot afford, care.

In the short term this may get worse. Expansion of elective egg freezing for preservation of future fertility, for example, unaccompanied by an increase in IVF laboratory capacity, further limits access to IVF for women and couples with infertility now. And while the panelists disagreed about how rapidly elective egg freezing is being adopted in the U.S., there was consensus that it is growing quickly (growth rates between 12% and 35% were cited in specific locations.)

Where do we find the solution to limited access to IVF? From the industry itself? From the insurance industry or employers? Policy makers? Coming: the case for entrepreneurship and market forces in the evolution of reproductive medicine.

Why We Need More Tech In High Tech Reproduction

Years ago my fund owned a large position in IVF practice management company Integramed, a public company at the time. My thesis was based on the upside potential for the company’s shared risk program, which offered multiple IVF cycles for a single upfront payment larger than that of a single cycle, with a refund of part of the payment if the couple or patient ultimately failed to conceive and deliver. I felt the program could be greatly expanded and be both very profitable for the company and help many more couples access care at lower financial risk.

At the time of our investment the shared risk program was used in a relatively small percentage of cases. The problem, as I saw it, was that the entry criteria for the program were too stringent, seemed arbitrary and not evidence-based, and that the only people allowed access to it likely didn’t need it in the first place. The program would end up charging more to patients or couples likely to conceive quickly than it would pay back those for whom the procedure did not work.

The Integramed network at the time accounted for a large percentage of all the IVF performed in the United States at the time. This footprint gave the company access to a huge database of actuarial data, information that could have been studied to much more precisely analyze the combination of inputs that would in turn predict cycle outcomes for individual patients and couples.

Which in turn would have enabled a rationally-designed payment plan that solved for the simultaneous goals of good outcome for patients and improved risk management for both the patient and the IVF program.

Which in turn would have attracted more patients, provided incentives to more IVF programs to join the Integramed network, and been a catalyst for growth for the company.

To the best of my knowledge, my ideas went no further than the “listen politely to your investor” stage.

Fast forward to 2018, and the opportunities to use data to improve access to IVF, improve outcomes, better define and allocate financial risk between patients and providers and motivate investment into laboratory capacity and program throughput are even more substantial. Except this time, industry is listening. Indeed, several of the panelists from the Columbia Business School Business Of Reproductive Medicine program last week are actively involved in implementing this idea.

Alan Copperman, for example, serves as medical director of Progyny, a fertility benefits company that designs and implements employee-based coverage for assisted reproduction, giving businesses the option of offering egg freezing and IVF as an employee benefit, by applying extensive domain knowledge and real actuarial data analysis to the rational design of programs that will be accessed, be successful, and be cost-effective. (disclosure: I serve as a member of the Progyny medical advisory board.) Similarly, Mylene Yao’s company Univfy analyzes an enormous amount of patient and clinic specific information to provide far more precise predictive data, that both patients and clinics can use to make rational decisions as to how to triage their resources.

When I was a practicing reproductive endocrinologist, I recognized that patients had very little objective data on which to base their expectations of success going into IVF. Faced with $20,000 or more and a month or more of what a patient called “the unpleasant extra job of being an IVF patient,” they found that the CDC Fertility Clinics Success Rates report was much better at population statistics than at individual predictions. Patients deserved then, and deserve now, more accuracy than multi-year age grouped, imprecisely defined diagnostic-grouped percentage outcomes offered.

Data aggregation and interpretation, predictive analytics and support for rational decision-making at the provider, payor and patient level represent a tiny fraction of the benefits of more sophisticated use of information technology in the efficient and cost-effective delivery of care in reproductive medicine.

How Entrepreneurs Will Move IVF Into The Future

Having spent eighteen years in women’s health as an ob/gyn and reproductive endocrinologist, I witnessed up close the human suffering from infertility, the limitations of in vitro fertilization (IVF) and the profound disappointment of prospective parents who could not afford treatment.

These reasons are more than enough to make you want to invest in innovation in assisted reproduction.

And there’s a good business case too.

To start with, the market is already there. Let’s review the numbers again. By almost any metric, the United States’ utilization of IVF is substantially lower than that of other developed economies. We perform far fewer cycles per capita than most European countries and Japan; IVF accounts for 1.5% of babies born in the U.S. versus over 4% in Australia. Overall, the slightly more than 200,000 IVF cycles we perform per year underserves the 7 million U.S. women with infertility.

The combination of high start-up costs, the limited number of subspecialty-trained reproductive endocrinologists and skilled embryologists, and the concentration of IVF programs in larger cities has resulted in an equilibrium state where most programs and doctors are busy, everyone is making a good living and new clinics are more often than not extensions of existing programs or the result of a large program absorbing a smaller one — business development moves that likely improve the quality of care, but do not expand access.

With a typical cost of $12–15,000 a cycle, IVF alone — not counting medications, precycle workups by ob/gyns, or ancillary costs — accounts for $2.4 to 3 billion of revenue. This likely underestimates the size of the industry. There are centers that charge much more than the average, and additional expenses related to egg donation, frozen embryo storage, and genetic testing of embryos can substantially increase the costs of a cycle.

$4 to 5 billion is probably more accurate.

That sum, while substantial, is rather small in comparison to other parts of the healthcare economy. While the costs of care for seven million American women with infertility is $4–5 billion, over $80 billion is spent on cancer treatment for fifteen million affected Americans. (Don’t get me wrong — I do not begrudge a penny of that spending for either group, nor am I implying any type of comparison between the suffering arising from the two conditions — I am merely putting aggregate spending for IVF in perspective.)

Is the IVF industry “right sized?” Or is there a case for layering seed and start-up investment on top of the private equity funding that has logically flowed into the consolidation of IVF in the U.S.?

What is the business case for investing in innovation in reproductive medicine? Should we be funding startups, seeding IVF tech companies and trying to disrupt the status quo?

Yes. Unequivocally yes.

Reason 1: Build it, lower the price a bit and patients will come. Lots of them.

As we’ve seen, experience in other countries, plus our own population statistics, implies that there is a very substantial latent demand for accessible, affordable IVF. We do not need to create a market; it is already there.

Reasons 2 and 2a: IVF for elective egg freezing, and IVF for prevention of genetic disease.

New markets are emerging, and we’ll need both expanded capacity and more efficient processes to make sure that the broad expansion of IVF to women and couples that do not have demonstrated infertility does not further limit access to existing patients.

Our Columbia Business School Business of Reproductive Medicine Panel included Susan Hertzberg, CEO of Prelude Fertility, an ambitious company founded by Martin Varsavsky that promotes, facilitates and provides egg freezing, genetic testing and proactive self management of women’s fertility, adding scale to a trend that has been gaining traction since 2012, when the American Society of Reproductive Medicine (ASRM) declared that egg freezing should no longer be considered experimental.

According to the US Centers for Disease Control (CDC), there were over 45,000 egg freezing cycles in the United States in 2015, a very substantial number in the context of the approximately 200,000 yearly cycles performed for infertility patients.

The panel also included Anne Morriss, CEO of Genepeeks, a company that provides greatly expanded preconception screening. IVF with PGD can be a very effective method of preventive medicine, and pays for itself. Compare a single egg retrieval for a young couple that yields sufficient healthy embryos for two, three or four embryo transfers at an aggregate cost less than $50,000 to the $300,000 yearly cost of Kalydeco, one of Vertex Pharmaceutical’s cystic fibrosis drugs.

IVF for disease prevention offers tremendous promise — as long as we have the IVF infrastructure to support it.

Reason 3: Companies have determined that infertility benefits are an important element in attracting and retaining highly skilled workers, and they are increasingly demanding efficient and cost effective care.

The IVF industry is unique in U.S. healthcare. It is not controlled by a huge hospital system / huge insurance company mega-contracting process where each individual procedure is a tiny part of an all-inclusive healthcare package designed to meet the needs of tens of thousands of people. IVF still follows a retail purchase model, and has been a sellers’ market. The emergence of disciplined large buyers reverses this trend, and hopefully makes IVF affordable for more patients.

So how do these trends translate into entrepreneurship opportunities? How could more cost-conscious IVF be a great business? Let’s list the ways.

Innovation that leverages nursing time with technology, particularly for patient education and communication, standardizes much of the protocol and cycle management decision-making with artificial intelligence, mechanizes many of the repetitive tasks performed in the laboratory, removing the wide variation in operator performance and coupled with an effective process optimization that eliminates a lot of the redundancy grandfathered into IVF cycles (do we really need all of those morning ultrasound scans, and all of those repeated blood tests every cycle?) — would create a different patient experience, maybe not as hands on, possibly more impersonal, but ideally one that gives patients the same likelihood of successfully conceiving and delivering a healthy child, while giving experienced doctors an opportunity to scale their programs, treating many more patients while staying profitable.

How profitable? If 4.5% of American babies came from IVF, as they do in Australia, we would be doing (using current pregnancy and delivery rates) over 400,000 more cycles, or up to $3 billion of increased revenue even if the revenue per cycle is cut in half. If we increase U.S. per capita utilization to that of Israel, again cutting prices in half, we would create over $6 billion of economic activity.

Yes, margins would be lower, but the same process improvements and efficiencies that make the expansion in capacity possible would counter some of the margin pressure, contributing further to industry growth.

More importantly, this would democratize assisted reproduction, bringing the benefits of best practices infertility care, fertility preservation, and assisted reproduction for the prevention of genetic disease to an enormous population, in a competitive marketplace.

Worthy goals indeed for entrepreneurship in reproductive medicine.