In research that could lead both to new ways to treat infertility and new types of contraceptives, scientists have identified molecules that help embryos stick to the wall of the uterus.
Timing is everything, the study shows.
By analyzing carbohydrate molecules on the surface of the uterus during different times of the female cycle and by identifying a protein, called L-selectin, on the surface of the embryo, researchers at the University of California, San Francisco, learned for the first time how the embryo sticks to the wall.
Susan J. Fisher said coatings on the uterus and on the surface of the embryo act like puzzle pieces that touch and quickly lock.
"One piece of the puzzle is a protein on the embryo and the other is a very specialized carbohydrate sugar structure," said Fisher.
The sugar molecule on the surface of the uterus is secreted for only a short time during a woman's monthly cycle and the embryo, with its L-selectin coating, must arrive at the uterus during this time.
"It has to take place in exact synchrony or you don't get pregnant," said Fisher, noting that failure to implant on the uterus is one of the most common causes of a failed conception.
"Only 50 to 60 percent of all conceptions advance beyond 20 weeks and of pregnancies that are lost, 75 percent represent a failure of implantation," she said.
With this understanding of implantation, researchers may find new ways to help women time their efforts to get pregnant, both naturally and in fertility clinics.
Fisher said it may be possible in fertility clinics to coat embryos with the sugar molecule and help uterus adhesion.
"If we can launch the implantation (process) in the culture dish then you might be able to implant fewer embryos and have greater certainty" of a successful pregnancy, she said. Currently, fertility clinics can prompt successful pregnancies 25 to 40 percent of the time. By more precisely timing implantation, based on the readiness of the uterus to adhere to the embryo, these chances could improve, said Fisher.
The new research may also help develop contraceptives that are not based on hormones, but on blocking the implantation of the embryo.
"A lot of women don't use the pill because of the hormonal effects," said Fisher. "If you had a drug that went directly to the molecules that control adhesion it would be not only very successful, but also have many less side effects."
Fisher said the new research may also help control the risk of pre-eclampsia, which is the most common cause of maternal death in the industrial world. She said the fundamental cause of the disorder is a shallow attachment of the placenta to the uterus wall. Normally, the placenta forms a strong connection to blood vessels deep within the uterus, but this fails to happen in pre-eclampsia. The placenta grows from both the uterus and the embryo and is the organ that provides nourishment and blood supply to the developing fetus. But it all starts with implantation on the uterus wall.
"We are theorizing that if the initial stages of adhesion are faulty then it could lead to less robust placenta formation," she said.
Pre-eclampsia can cause maternal high blood pressure, kidney failure, swelling, seizures and death.
Dr. Phyllis Leppert, chief of the reproductive science branch of the National Institute of Child Health and Human Development, said the discovery by Fisher and her co-authors "is a breakthrough" that may lead to fundamental new treatments for pre-eclampsia and for a major cause of infertility, poor adhesion to the uterus after conception.
"This is a new lead that we can pursue," she said.
By Paul Recer