The primary focus of the Zouves Foundation for Reproductive Medicine is the study of early human development and implantation with the objective to improve the treatment of infertility. We have been aggressively moving toward that end since January of 2016.
For more than two decades the Society for Assisted Reproductive Medicine has recommended its members to transfer a single embryo in order to avoid the complications of pregnancy associated with multiple gestations. This has prompted an investigation of methods that would allow us to prioritize embryos with the greatest likelihood of implantation after uterine transfer. The initial method of selecting embryos for transfer was based wholly on morphological criteria that established pregnancies in the low 20-percentile range when a single embryo was transferred. Beginning in the late 1990s, IVF treatment moved toward prioritizing embryos for replacement based upon a 9 chromosome-screening test that predicted embryo chromosome normalcy with an accuracy of approximately 70 percent. This technology has continued to advance and today most embryos are prioritized for replacement primarily by assessing their 23 chromosome normalcy and then secondly by their morphology. The pregnancy rate has subsequently improved significantly to approximately 60 percent per embryo transferred and the acceptable use of single embryo transfer has now been realized for the first time in the history of IVF. This stunning improvement however, leaves 40 percent of embryos that are chromosomally normal and of good morphological quality unaccountably destined for degeneration and implantation failure. The aim of the Zouves Foundation is to identify why this should be so and ultimately advance our embryo implantation rates closer to 100 percent.
The Zouves Foundation benefits directly from the precedent set by the Zouves Fertility Center’s investment in promising technologies that improve IVF outcomes for our patients. ZFC was an early adopter of pre-implantation testing (PGT) technologies and is singular amongst United States private IVF clinics in that it retains the expertise and current technologies to offer PGT in-house, and has in fact done so since the early 2000s. As a result, the Zouves Foundation has a unique and immensely valuable resource in the extranumerary frozen embryos donated to research. When we include data on embryo chromosomal profiles and pregnancy outcomes from ZFC, we are confident that Zouves Foundation research is well placed to make significant and valuable contributions to the rapidly burgeoning fields of genetic sciences here in the heart of the San Francisco Bay Area.
In the brief history of the Foundation we have strived to understand embryo selection through chromosomal and cellular normalcy and our investigations have already produced a better understanding for an appropriate measurement of the intracellular organelles that produce the energy within the cytoplasm of embryos. This published work on the measurement of mitochondrial DNA copy number was recognized as a seminal contribution by the Journal of Fertility and Sterility in 2017, and it is another step toward understanding the role of mitochondria in early embryo development and their potential as an embryo selection tool.
Additional work by the Zouves Foundation has been presented at poster sessions at the American Society of Reproductive Medicine and International Preimplantation Genetic Diagnosis symposia; we have examined the use of a laser to safely excise cells from embryos and the concomitant effects on DNA stability and the DNA sequencing profile. In a further study we have been asking difficult questions about chromosomal profiles (karyotypes) of the two early embryo cell types that have developmentally different endpoints; trophectoderm cells that form the placenta and the inner cell mass cells that form the baby. Just a cohort of trophectoderm cells is biopsied to determine the embryo’s genetic profile, and in our hypothetical model it is possible that the inner cell mass and the trophectoderm could have discordant karyotypes, leading to a genetic diagnosis that does not represent the embryo’s true capability to implant. While the probability of this event is extremely low, it could mean that in some rare cases an embryo diagnosed as abnormal may lead to a normal birth.
These important questions address the embryological techniques and molecular biology that underpin the earliest beginnings of a nascent human life. To that end, in our ongoing search for enhanced methods to prioritize embryos for transfer, we are initiating collaborations with scientists at Princeton University to look for specific genetic variants that may predict embryo implantation potential, as well as the expression of certain stress-related genes that may identify embryos that are developmentally compromised. Additionally, the embryology and preimplantation screening capability of the Zouves Foundation laboratory has already attracted the attention of a San Francisco Bay Area biotech company and we have been host to researchers developing microfluidic DNA sequencing systems for their potential research and commercial application.
In less than 2 years the Foundation has demonstrated that it can set a scientific agenda and carry it out. Through consistent and careful work our experiments have better defined early embryo development and improvements to the IVF process have already been successfully incorporated. We have contributed quality research to scientific meetings in the United States and in Europe, and we have received accolades for making a seminal contribution to the treatment of patient infertility. The Zouves Foundation is excited for the potential of this important research to continue, and for the beneficial advances we will bring to the human IVF community.