Yale Fertility Expert finds Genetic Markers of an Egg's Maturity

Fertility experts like Pasquale Patrizio, M.D. of the Yale School of Medicine have long been interested in understanding why so few human eggs harvested during in vitro fertilization result in pregnancies.

“The two big questions are why so few eggs produce live births and can we one day identify the best one among the many that look alike?’’ Patrizio said. “To do so we needed to understand the genetic make up of eggs first.”

In a paper published in the current issue of the American Journal of Obstetrics and Gynecology, Patrizio and a colleague have identified some possible molecular suspects.

An extensive genetic analysis by Patrizio, professor of obstetrics and gynecology and director of the Yale Fertility Center, and former Yale colleague Dagan Wells, now at the University of Oxford in the United Kingdom, showed significant differences in gene activity among eggs at different stages of maturity. Patrizio and Wells conducted analysis of gene expression in immature eggs, mature eggs developed in culture in the laboratory, and eggs matured in the ovary within their own egg-shell.

They found that, eggs that matured in culture, as opposed to eggs that were already mature at the time of harvesting, tended to lack gene activity normally involved in the development of the cytoplasm of the egg, or the area outside the nucleus. Furthermore, they compiled a list of mRNA-mediated gene expression changes that take place as the eggs matured.

The study is significant for many reasons, say the researchers. First it provides the most comprehensive and detailed information about the genetic make-up of human eggs at different stages of maturity. Second, it provides gene expression profiles that will make it possible to identify eggs with exceptional developmental capacity. Third, it reveals that eggs harvested while still immature and then matured in lab dishes, a practice known as vitro maturation, display significant differences in gene activity when compared to already mature eggs.

The findings of significant differences in the genetic profiles of eggs matured in lab dishes as opposed to eggs matured within the ovary may be a clue that the current culture conditions are suboptimal, and this can also explain the lower pregnancy rates seen with the process of in vitro maturation, Patrizio said.

Fertility clinics have started to offer in vitro maturation to some patients because it requires fewer drugs and therefore has fewer side effects such as ovarian hyperstimulation.

“However, the advantage of using fewer days of stimulation and fewer drugs, may be negated by the observation that these eggs are unable to properly complete their maturation process and that important proteins manufactured during in vivo maturation are missing,” Patrizio said.

The results of this study will help researchers develop ways to better culture immature eggs and pave the way to identify which ones might be most likely to lead to live births, he said.