SBIR-STTR Award

Since the first in vitro fertilization baby in 1978, IVF has brought significant benefit to tens of thousands of otherwise infertile couples. Behind the success stories lies a per-cycle success rate of only 23%, and a high rate of multiple gestation, with significant emotional, health and economic costs. Present assisted reproduction techniques for egg quality assessment consist of visual inspection of morphology using Hoffman or DIC microscopy, and some genetic testing. There is compelling evidence that morphology of the phase II meiotic spindle can be used to assess viability. However, conventional contrast-enhancement techniques for revealing spindle morphology are invasive and incompatible with clinical IVF. An imaging technique that reveals spindle morphology non- invasively and software that uses the morphometric information to predict outcome might provide an essential new tool for reducing uncertainty in the IVF process. Birefringence imaging with the PolScope microscope reveals the meiotic spindle non-invasively by measuring birefringent retardation at each image point in the field of view. Our goals in Phase I are to confirm the PolScope accurately reveals spindle morphology by comparing with fluorescence confocal images, and develop multiple regression models to assess the PolScope's utility for predicting IVF outcome based on the morphometric data. PROPOSED COMMERCIAL APPLICATION: If we can demonstrate utility for predicting IVF outcome, we will then develop a commercial instrument that would aid in the grading of eggs, which should be of significant interest to the 300 or more IVF clinics in the US, and the 500 or more IVF clinics outside the US. We would also expect interest from veterinarian clinics.

The objective of this Phase II project is to develop a more effective tool for assessing the development potential of human oocytes and to reduce the emotional, health, and financial costs of low IVF success rates, presently -25% per cycle. To compensate for these low rates, as many as three or more embryos are transferred to the mother-this practice is a leading cause of multiple and often premature births. Low success rates also lead to multiple, emotionally draining and expensive interventions. An ability to select high quality oocytes is critical to achieving successful outcomes. The main premise of this application is that reliable quantitative analysis of oocyte structures can improve IVF techniques, and proposes to apply to this task a new type of microscope that measures birefringence, an optical property exhibited in many cellular structural elements. Compared to images provided by traditional Hoffman or DIG optics presently used for oocyte assessment, non-invasive birefringence imaging using CRI's unique liquid crystal polarized light microscope dramatically and quantitatively highlights the meiotic spindle and other cellular structures by measuring birefringence retardation at each image point in the field of view. Phase I demonstrated that birefringence imaging of oocyte structures provides information that correlates significantly with embryo development and, ultimately, clinical outcome. Spindle visualization was also shown to be useful in assessing viability of cryopreserved oocytes, another critical and otherwise unsolved problem. Phase II specific aims include extending functionality to allow quantitative measurement of birefringence in three dimensions, adding features to make operation more suitable to the clinical IVF setting, developing an appropriately sized and treated glass-bottom dish, developing software tools and algorithms that extract additional quantitative information about viability and condition, and working with three beta-sites to test systems and provide vital feedback on effectiveness and operation.

Thesaurus Terms:
biomedical equipment development, birefringence, cell morphology, clinical biomedical equipment, in vitro fertilization, mitotic spindle, oogenesis, ovulation detection /prediction, reproductive development biomedical automation, cell population study, computer program /software, cryopreservation, fertility, health care cost /financing, meiosis, noninvasive diagnosis biotechnology, liquid crystal, mathematical model, optics