UH-Japan team improves fertilization success rate

University of Hawaii researchers and colleagues in Japan have taken another step to improve a reproductive technique to help couples trying to have babies.

Their discovery brings the process closer to natural fertilization, said Ryuzo Yanagimachi, professor emeritus of anatomy and reproductive biology who made international news with the cloning of mice in 1998.

Kazuto Morozumi, obstetrician/gynecologist from Japan, has been working with Yanagimachi at the John A. Burns School of Medicine to improve intracytoplasmic sperm injection, a technique developed to help a couple undergoing in-vitro fertilization because of male infertility.

The technique involves injecting a single sperm to fertilize an egg, unlike artificial insemination and in-vitro fertilization, which require thousands or millions of sperm.

The UH Institute of Biogenesis scientists discovered last year that removing the acrosome, a caplike structure covering the sperm's head, before injecting sperm could increase success.

In their latest research, they have found that simultaneously removing the sperm's plasma membrane and acrosome before injection improves the egg's activation and embryonic development.

Morozumi is lead author of a paper on their findings published this week in the Proceedings of the National Academy of Sciences.

Commenting on the research in a companion paper, Eduardo Roldan, with a reproduction group at the Museo Nacional de Ciencias Naturales in Spain, said the results suggest success could be improved in humans and domestic or wild species.

Yanagimachi said the microsurgical sperm injection method "has been amazingly successful in humans and mice."

Using the mouse as a model, he said the scientists found activation of the egg "is faster and more orderly" when the sperm's plasma membrane is chemically removed with the acrosome before injection.

The embryo also develops better in the womb, he said. "This is not surprising, because this fertilization is slightly, yet significantly, closer to natural fertilization than conventional ICSI. ... It's not perfect, of course, but this may help."

Morozumi will return to Japan at the end of the year and try to arrange clinical trials with humans, Yanagimachi said.

Dr. Thomas Huang, laboratory director of the Pacific In Vitro Fertilization Institute, also has been doing preliminary work with Yanagimachi to see about applying the technique clinically to humans. A proposal is being developed for the Institutional Review Board before proceeding with trials, Huang said.

Meanwhile, "We're still trying to figure out the best methods to use to adapt to a human situation, which is a different kind of sperm," he said.

The acrosome is so small in human sperm that it can't be seen easily by microscope, and requires special labor-intensive staining procedures, he said.

In normal fertilization, the sperm and egg membranes fuse, Huang said. "If we just bypass fusion and inject the sperm, maybe it's harder for the egg to process information the sperm is bringing in.

"If we can remove the membrane, maybe the egg can recognize things that normally occur in fusion," he said. "We're hoping this will provide a mechanism to allow for more natural interaction of sperm with egg."

Huang said this might have implications for subsequent development of the embryo. A more natural egg activation process could be related to more robust embryonic development, he said.

Huang said intracytoplasmic sperm injection has allowed people to be treated for infertility who couldn't be treated before.