Gamete/embryo development and genetics

Infertility in women may be caused by various pathological and/or biological changes in their reproductive system. The primary interests of our research are the following: to better understand the mechanisms that regulate mammalian oogenesis and embryo genesis, to improve assisted reproductive technologies (ART), and to assist infertile couples in having healthy children. Three major projects are ongoing:

1. Oocyte maturation in vitro and nuclear-cytoplasm interactions. A common protocol in many IVF clinics for ovulation induction employs a regimen of hormones over several days, thus inducing the growth and maturation of several follicles within the ovary. Such a procedure allows more than one mature egg, an average of ten, to be retrieved. Unfortunately, not all women will respond well to the stimulation regimen. One promising approach to overcome these problems may be to collect primordial germ cells or immature eggs from small follicles, and mature these eggs in vitro. Furthermore, critical roles of cytoplasm (maternal signals) in early embryonic development have been recognized. Changes in cytoplasm of oocytes form women at advanced maternal ages (AMA) may be associated with a decrease in certain components. A possible remedy may be to replace a portion of the cytoplasm of oocytes from AMA women with cytoplasm of oocytes from younger women. Such a strategy may correct the deficiency of some components, thereby increasing the quality of the oocytes of AMA women; at the same time identifying key elements that cause the deficiency.

2. Embryo development in vitro. Another important approach to improve the success rate of ART is to provide optimal culture conditions for early embryos. Though human embryos can survive in a simple medium for a few days in vitro, their viability may be compromised due to a sub optimal environment. Co-culture embryos with helper cells, such as granulosa or endometrial cells, may improve embryo quality. The effectiveness of such a co-culture system is being examined and the possible mechanism of somatic cell and embryo interactions are under investigation.

3. Preimplantation genetic diagnosis (PGD). PGD involves biopsies of polar bodies from mature eggs (PB-I) and/or fertilized oocytes (PB-II), as well as one or two cells from early cleavage stage embryos. Before embryo replacement diagnosis are based on analyzing polar bodies and/or single cells, either by fluorescence in situ hybridization (FISH) with multiple proves which determine chromosomal abnormalities, or by polymerase chain reaction (PCR) to detect single gene mutations. Efforts are currently being taken to improve accuracy, thoroughly examine all steps involved, as well as assess the efficiency of PGD. Based on a precise diagnosis, germinal gene therapy may be introduced in the future.