IVF Post Repeal Of Roe v Wade: The Practical And Apolitical

IVF Beyond Borders, Return of The Polar Body?

Like many of my ob/gyn colleagues, I have strong feelings about the Supreme Court’s looming decision on Roe v. Wade. But this piece is not about politics — mine or anyone else’s. Let’s address a more practical issue: if the law changes tomorrow, what do we do the day after to maintain quality of care and probability of good outcomes?

Those outcomes are challenged because one of the most important aspects of successful IVF — the ability to mature and develop a number of eggs in parallel during a single cycle — is at odds with a common element of many of the proposed post Roe v Wade repeal laws, the so-called “personhood” provisions, which “give from the moment of sperm-egg fertilization, inalienable rights, equality of justice, and due process of law protection to embryos.” (https://resolve.org/about-us/policies-and-positions/)

Much like the human reproductive system that it treats, one that creates many more mature eggs and many more embryos than will result in viable pregnancies, IVF matures and fertilizes many eggs per cycle. Like in nature, some will develop into viable pregnancies; most will not. Practically speaking, overcoming this inefficiency had to be engineered into the IVF procedure for it to have any chance of working at scale. Forty years of steady progress suggest that we made the right decision. What happens if we have to un-make it now?

What specific actions can we take to insure that existing and future patients get treated?

What can we do, in the laboratory and in the clinic to ensure continuity of care, and continued good, improving outcomes?

IVF Beyond State Borders: Clinic Strategy

In the clinic, we can learn from our European colleagues how laws that stratify access to specific procedures and techniques ripple through the IVF ecosystem in a logical and organic fashion. In Western Europe, strict limits, or outright bans, on IVF for same sex couples, use of preimplantation genetic testing, and use of egg donors and surrogate carriers lead to large groups of patients traveling from France, Italy and Germany to Spain for treatment. A similar regulatory arbitrage would likely send patients away from states with strict IVF limitations to states with more accommodating policies. Further, patients with stored and frozen eggs and embryos would likely transfer them for storage to facilities in IVF friendly states.

In the short term, while the laws are debated, adopted, and challenged, the IVF infrastructure needs to prepare for the challenges of mobilizing, tracking and safely transporting potentially tens of thousands of specimens. Thankfully, advances in cell biology outside of reproductive medicine, in oncology, for example, have resulted in a rapidly maturing logistics network developed specifically to address this challenge. Within the IVF industry itself, consolidation of clinics into multi-site practices, linking centers in different states and regions, could help. In theory, clinics operating under the same corporate umbrella should be able to design an efficient procedure for moving specimens from one place to another, as both a matter of good patient care and service and for the purely corporate goal of patient retention.

Polar Body Resurrection, Better AI, Getting Sperm to Talk: Lab Strategies

Equally important, but more challenging, are developing techniques in the laboratory that can optimize treatment within the new constraints and limitations that these new laws will impose.

The most pressing need will be to improve the efficiency of the embryo to viable pregnancy ratio. Let me restate: much like the human reproductive system that it treats, one that creates many more mature eggs and many more embryos than will result in viable pregnancies, IVF matures and fertilizes many eggs per cycle. Like in nature, some will develop into viable pregnancies; most will not.

If we lose the ability to mimic nature in this way, how do we minimize the negative outcome effects of a one egg, one embryo at a time system?

One strategy is to move genetic analysis upstream. Just as euploid embryos have higher live birth rates than aneuploid embryos, euploid oocytes should correlate positively with euploid embryos. Of course we lose the data from the sperm, and of course we will not detect errors post fertilization — the very reasons why oocyte genetic assessment by biopsy followed by FISH/CGH/NGS or whatever has not been adopted clinically.

The need for pre-fertilization oocyte assessment gives new relevance to work being done by several groups using advanced imaging with machine learning to detect correlations between pre-fertilization oocyte appearance and ultimate embryo outcomes. The argument against funding these projects has always been that implicit in the practice of IVF is a well-functioning means of assessing which oocytes will turn into good embryos; that is, fertilize them and watch to see which oocytes turn into good embryos.

Could other artificial intelligence approaches help? My pedestrian not-quite-a data-guy guess is that the relatively small time interval for doing serial measurements (metabolic parameters in media for example) of physiologic parameters that could correlate with egg quality suggests to me that there’s not a lot of potential there there, but I hope to be proven wrong.

I also hope that my pessimism about being able to extrapolate truly helpful information about individual sperm potential by non destructive assessment being is disproved; we’ve been trying to get sperm to talk to us for decades, but no matter how many ways we try to extrapolate sperm genetics and sperm regulatory capacity post fertilization from observable motility and morphology, we always get the same answer: now matter how closely you look at the outside of an automobile, you can’t tell what’s in the trunk.

Someone prove me wrong please. Because pairing a truly predictive external sperm assessment with an oocyte aneuploidy screen could in theory lessen the imposed handicap of one embryo at a time IVF practice.

There are probably a lot better ideas for IVF innovation in a one embryo at a time world than my simple geographic arbitrage, resurrection or the polar body biopsy and sperm function moon shot. And IVF Team USA has a forty year record of moving forward.

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David Sable

bio fund manager, Columbia prof, ex-reproductive endocrinologist, roadie for @PriyaMayadas