Grant: Operating Grant

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive procedure in treatment of male infertility. It involves the injection of a sperm into an oocyte to facilitate fertilization. Because natural barriers to fertilization are bypassed, ICSI may facilitate the transmission of genetic (DNA related) and epigenetic (DNA independent mechanisms that influence gene expression) abnormalities to the next generation. These abnormalities include a deviation from the normal complement of chromosomes (46 units of compacted DNA) in a cell. There is also concern that the injection procedure of ICSI disrupts the organization of the oocyte and this may effect the development of the resulting embryo. These alterations in pregnancies can potentially lead to pregnancy loss, birth defects, and low birth weight. We hypothesize that ICSI presents both procedure-dependent and independent risks to the fetus. We will investigate of the incidence of chromosomal abnormalities and epigenetic changes in the pregnancies of three assisted reproductive techniques - intrauterine insemination, in vitro fertilization (IVF), and ICSI - and evaluate how the differences among the techniques, namely the use of cell culture, the genetic background of different types of infertility involved, and the method of fertilization, effects the development of these abnormalities. Furthermore, we will examine key steps of cell division in the development of sperm when a chromosomal abnormality in a child is determined to be passed on from the father. Our long-term aims are to identify chromosomal and epigenetic risk factors to conceptions of ICSI, and to develop strategies to prevent abnormal offspring from being born after ICSI.