Description): Infertility affects more than one in seven couples wishing to conceive and, in about half of these, the problem is an intrinsic abnormality associated with the sperm'. Intracytoplasmic sperm injection (ICSI) bypasses many barriers to male infertility, even though many biological, particularly genetic, factors required for normal sperm function are poorly understood. It is possible, perhaps likely, that (some) genetic abnormalities that preclude normal fertilization are bypassed by techniques in which sperm are injected directly into the egg. These genetic abnormalities could include aneuploidy, structural chromosome abnormalities, or deletions and mutations in genes associated with sperm function. As a result of ICSI, sperm potentially genetically aberrant can now fertilize oocytes. The overall goal of this study is to identify genetic abnormalities in somatic and germ cells of males with severe oligoasthenoteratozoospermia (OAT) and evaluate the association of such aberrations with the outcome of pregnancies following ICSI. Preliminary data indicate there is an additional risk associated with ICSI. The investigators intend to improve the safety of ICSI by determining whether the procedure carries a risk for the transmission of genetic abnormalities to offspring. They hypothesize that genetic abnormalities in the sperm of males with severe OAT will lead to a higher frequency of miscarriage and may contribute to an increased incidence of genetic abnormalities in the offspring of such males undergoing ICSI. They propose to conduct a study with the following three specific aims: (1) To determine the frequency and type of somatic karyotypic abnormalities in OAT patients. (2) To determine whether sperm and somatic cells from OAT males are aneuploid and/or have deletions in genes associated with spermatogenesis (DAZ or its autosomal homolog, DAZH). (3) To correlate outcomes at different stages of pregnancy, including oocyte fertilization, implantation, pregnancy duration, miscarriage, and delivery with the genetic abnormalities observed under specific aims 1 and 2. While ICSI is the method of choice to treat male factor infertility, little is known about its safety and efficacy. The results of this study may provide additional data that will clarify the risks associated with ICSI.
