The NICHD seeks to assure that all children are born healthy and wanted, and that couples can have the families they want when they are ready for them. During the previous year, NICHD-supported scientists gained new insights into the biology of reproduction. These insights may lead to the development of new contraceptive methods.

A Possible New Approach to Contraception. Oocytes, or egg cells, must mature before sperm can fertilize them. This maturation starts with a surging release of luteinizing hormone (LH) from the pituitary gland. In turn, LH activates an enzyme called phosphodiesterase (PDE). This enzyme reduces the high levels of another chemical, cyclic adenosine monophosphate, which keeps oocytes in an immature state. These findings suggest that PDE plays a key role in allowing fertilization to occur. Researchers have known that in rats and mice given a compound that inhibits PDE3 (a form of PDE), the oocytes fail to mature and cannot be fertilized. Until recently, however, they didn't know if the inhibitor would work the same way in non-human primates, thus offering insights into what may happen in the human body. Now, NICHD-supported researchers found that the PDE3 inhibitor also prevents monkey oocytes from maturing. This finding provides the basis for researchers to examine whether interrupting maturation of the egg cell could lead to a new, safe, and effective contraceptive approach for women, which would work well before fertilization occurs.

Much of NICHD's research focuses on ensuring that women can carry their pregnancies successfully to term. Last year, researchers provided new insight into the events that must take place before a pregnancy can be established, which could lead to new treatments for infertility. Other studies provide insights on guidelines concerning the duration of labor.

Discovering How an Embryo Attaches to the Uterus. A recent NICHD-supported study sheds new light on understanding the first biological steps needed to establish a successful pregnancy. About six days after fertilization, the embryo, or blastocyst, is shaped like a sphere. Its surface is composed of a layer of specialized cells called the trophoblast, which later gives rise to cells that form the fetus' part of the placenta (the placenta is made up of both maternal and fetal tissue). The trophoblast is coated with a protein known as L-selectin, while the wall of the uterus is coated with carbohydrate molecules. Researchers uncovered evidence that as the blastocyst travels along the uterine wall, L-selectin on its surface binds to the carbohydrates on the uterine wall, until the blastocyst gradually slows to a complete stop. The process is similar to a tennis ball coming to a stop after rolling across a syrup-covered table. Only after the binding takes place, can the fetus implant itself in the uterine wall and a pregnancy begin. This finding may lead to insights into early pregnancy loss and the life-threatening complication of pregnancy known as preeclampsia, both of which may result from failures of the embryo to attach properly to the uterine wall.

Moreover, the finding may lead to a better understanding of some cases of endometriosis-associated infertility. Endometriosis is a disorder in which endometrial tissue-tissue that normally lines the inside of the uterus-begins growing in other parts of the abdomen, such as the outside of the uterus, ovaries, or intestines. Endometriosis affects 10 to 15 percent of women of reproductive age, and is a major cause of infertility in women who have difficulty becoming pregnant.[1] Another NICHD-supported research team found that women with infertility due to endometriosis have very low levels of the enzyme that makes the ligand for L-selectin. The ligand is a rubber-band like molecule that tethers L-selectin to the uterine wall. Researchers believe that without this enzyme, the embryo cannot attach to the uterine wall and a pregnancy cannot begin. The finding may lead to new therapies to treat women with endometriosis-related infertility.

New Standard for Labor and Delivery. More women are giving birth by cesarean section than in previous years, with more than one-fourth of all pregnant women, 26.1 percent, undergoing the procedure in 2002, up from 20.8 percent in 1997.[2] Such factors as a woman's age and general health play a role in doctors' decisions to perform a cesarean section. A recent NICHD study, however, shows that the criteria on which doctors base their decision may no longer apply. Since the mid-1950s, physicians have based labor and delivery practices on the Friedman labor curve, a mathematical model depicting how the stages of labor should progress during normal delivery.

However, on average, the characteristics of women giving birth today differ markedly from the population used to devise the Friedman labor curve. Compared to 50 years ago, obesity is far more prevalent, and women give birth later in life. Recently, researchers examined the pattern of labor progression in women in the 1990s giving birth for the first time. The researchers concluded that the Friedman criteria may be too stringent to determine when labor is proceeding much slower than expected. Moreover, the Friedman criteria may not apply to arrest disorders of labor, where the cervix does not dilate for two or more hours. In essence, researchers found that, for today's population of women, labor progressed more slowly than what was once identified as "normal" in the Friedman curve. These findings could have a profound impact on decisions about the need for cesarean delivery.

Compounds Prevent Alcohol from Damaging the Fetus. As many as 12,000 babies are born each year with fetal alcohol syndrome.[3] It is considered the most common non-hereditary form of mental retardation. Currently, however, no medication exists that can prevent alcohol's harmful effects on the developing fetus. This may change now that scientists from the NICHD and the NIMH recently found that NAP and SAL, the active peptides from two brain proteins known to protect nerve cells against a variety of toxins, also protect mouse embryos from ethanol-induced fetal death and growth abnormalities. The researchers also discovered that these peptides interfere with the way ethanol disrupts the chemical ties that hold cells together. NAP protected cells to a greater degree than did SAL, completely preventing ethanol from breaking these chemical ties, even in the presence of ethanol concentrations that kill cells. These discoveries strengthen the case that ethanol causes birth defects by interfering with cell adhesion. Understanding this process may help researchers design drugs to prevent some of the effects of fetal alcohol syndrome.

Fetal Origins of Adult Disease. Obesity, type 2 diabetes, high blood pressure, and heart disease are becoming increasingly common in the United States. Researchers want to understand whether the environment in the womb plays a role in the development of these disorders during adulthood. Recently, NICHD-supported researchers studied the adult children of mothers who received dietary advice during their pregnancies in 1967-68. The women were told they could prevent high blood pressure by consuming one pound of red meat per day and to cut back on carbohydrate-containing foods like bread and pasta during the second half of their pregnancies.

Researchers found that the more meat the women consumed during pregnancy, the higher their adult children's stress hormones were and the higher their blood pressure readings. Stress hormone levels were also higher in the adults whose mothers consumed few green vegetables during their pregnancy, with the highest levels found in those whose mothers consumed the highest amount of meat and the least amount of green vegetables. This research adds to the theory that adult diseases may have their origins in fetal life, and offers new insight into the kinds of diet women need to maintain healthy pregnancies.