Prof. Pasquale Patrizio - Director Yale Fertility Center; Professor of Obstetrics, Gynaecology and Reproductive Sciences, Yale University
Dr. Patrizio is Professor of Obstetrics and Gynecology, Director of the Yale Fertility Center and Fertility Preservation program. He is board certified in OB/GYN, REI, and Andrology. In addition he has a master in Bioethics and is certified as High Complexity Laboratory Director (HCLD). His clinical interests include: Improving the efficiency of ART, IVF and ICSI and Expand fertility preservation options. His translational research is devoted to developing non invasive markers to assess the biological competence of oocytes (aneuploidy) and to unravel the mechanisms of oocyte senescence. In addition his lab developed the methodology to freeze whole human ovaries and is currently collaborating to the development of methods to lyophilize gametes, chromosomes and human embryonic stem cells (hESC).
Dr.Patrizio has authored 144 peer reviewed publications, 220 abstracts, 66 chapters, and in addition has edited two textbooks, including a popular Atlas of Assisted Reproduction, six e-books and three scientific videos. He is associate editor of Reproductive Biomedicine on line and Journal Assisted Reproductive and Genetics and serves on the editorial board of AJOG and www.IVF-worldwide.com. Dr. Patrizio garnered a number of awards and recently (Nov. 2014) received the patient advocacy awards from Resolve. He is currently President of the International Society for Fertility Preservation (ISFP) and is serving as Clinical director for SART (ASRM).
Project: Identification of novel markers of human oocyte aging via non-invasive RNA sequencing analysis of cumulus cells
The quality of human oocytes is the main determinant for the success of in vitro fertilization (IVF) treatments. Despite remarkable advances in IVF and in the laboratory setting, the success rates for women 40 years or older are disappointingly low. The leading cause for the low success is oocyte senescence and poor oocyte quality. Yet, the molecular mechanisms underlying oocyte ageing remain poorly understood due to the lack of suitable animal models and the limited availability of human oocytes. This gap in knowledge adversely affects the outcome of IVF and without understanding the root causes of oocyte ageing it is impossible to devise protocols and strategies aimed at improving success rates and avoiding multiple, ineffective, IVF cycles that are both psychologically stressful and physically burdensome.
Previous studies suggested that zygotes from aged mammalian oocytes interrupt their normal developmental program soon after fertilization and undergo programmed cell death or apoptosis. In human oocytes the suggested triggers of apoptosis are the accumulation of reactive oxygen species (ROS), abnormal Ca2+ levels and a prominent decline in MPF and MAPK kinase activity due to a decrease in mitochondrial function. However, it is still unknown how these events are initiated and modulated within the follicular unit. Our preliminary data are strongly pointing to the cumulus oophorus cell complex (CC) as the main player in keeping homeostatic regulation of the ovarian microenvironment. Our preliminary data support the concept that age-related changes in CC function are the primary drivers of the mechanisms responsible for apoptosis in ageing oocyte.
Comparing gene expression in CC cells from younger and older women on HighSeq pair-end Illumina platforms, our preliminary findings seem to favor the hypothesis that inefficient activation of Hypoxia-inducible factor 1 (HIF-1a), an important regulator of ovulation, halts the formation of new blood vessels in the growing follicle and results in a low oxygen (hypoxia) environment (high iNOS) in the follicular units of ovaries of older women. Such environment is detrimental to the stability of the organelles within the oocyte, such as the meiotic spindle and mitochondria, whose roles are to allow proper chromosomal segregation and maintain the energetic balance to assure the embryonic development.
The objective of this grant is to further characterize the molecular signatures of CCs responsible for oocyte senescence and to assess whether the identified markers of hypoxia can be used as diagnostic tools to optimize oocyte selection during IVF.