Infertility affects both men and women and can stem from a number of causes. A variety of treatments for infertility are available, but they are not effective for all individuals.
Addressing the issues related to infertility in both men and women is a central part of the NICHD mission. To this end, the NICHD conducts and supports research on the causes of infertility and on new treatments to help individuals with infertility achieve pregnancy.
Institute Activities and Advances
Researchers at and supported by the NICHD are investigating the causes of infertility and identifying new effective treatments. One line of research examines the contributions of environmental factors to infertility. Another explores how the physical changes associated with diseases, such as endometriosis, relate to infertility. Investigators are also studying why African American women have lower success rates using assisted reproductive technology. In addition, research is being conducted to determine new ways to preserve fertility in women undergoing cancer treatments and to better understand the effect of aspirin on live-birth rates.
Research on the effects of environmental factors on infertility is conducted in the NICHD's Division of Intramural Population Health Research (DIPHR). For example, researchers in the Division collaborated with scientists at the University of Buffalo to study the relationship between hormone levels and oxidative stress during the menstrual cycle to elucidate the effects of diet, smoking, and caffeine on fertility. DIPHR scientists also studied the link between psychological stress and infertility in women. Additionally, DIPHR scientists are looking at the effect of environmental toxins and lifestyle factors on men and women's fertility. The Longitudinal Investigation of Fertility and the Environment (LIFE) Study is examining the long-term effects of lifestyle factors, including stress, cigarette smoking, caffeine intake, and alcohol usage, on fertility. Recently, researchers found that couples with high levels of exposure to persistent chemicals, like polychlorinated biphenyls, take longer to conceive.
The Epidemiology Branch within DIPHR conducts research and provides services and training. Its epidemiologic research focuses on reproductive, perinatal, and pediatric health endpoints to identify underlying etiologic mechanisms, at-risk subgroups, and interventions aimed at diagnosing or treating disease. An ongoing investigation, called the Effects of Aspirin on Gestation and Reproduction (EAGeR) Study, is investigating the effects of aspirin on blood flow and placental health to reduce the risk for adverse pregnancy events, such as early pregnancy loss and preterm delivery.
The Unit on Reproductive Endocrinology and Infertility (UREI) in the Division of Intramural Research (DIR) is also actively researching both treatments for and causes of infertility. For example, women and girls with cancer who undergo chemotherapy treatments are exposed to chemicals that can affect the ovaries and lead to infertility. Studies conducted by UREI scientists have examined ways to prevent this damage in women who undergo chemotherapy. Another study conducted by UREI scientists examined procedural differences in assisted reproductive technologies that might account for differences in pregnancy rates among African American women and whether access to care and economic issues affect use of the technologies by minority women.
Intramural scientists within the Program in Reproductive and Adult Endocrinology at the NICHD are examining possible causes and treatments for infertility associated with POI. Animal studies have explored molecular pathways involved in the loss of ovarian function and ways to intervene within the pathways to prevent loss of ovarian function. These investigators have studied women with POI to better understand the features of the disease, how it causes infertility, and how infertility can be treated in these women.
The NICHD Fertility and Infertility (FI) Branch, within the Division of Extramural Research (DER), supports research on a variety of topics related to infertility.
Preserving fertility is a topic of considerable interest at the Institute. Current investigations address the concerns of fertility preservation for men, women, and children, for circumstances covering cancer treatment and certain non-cancer conditions. Specifically, Institute-sponsored research investigates measures to prevent gamete damage, options to restore fertility after damage, developing biomarkers of gamete reserve, and the developing technologies that will enable reproductive-age adults to have biological children. One FI Branch-supported study found that granulocyte colony-stimulating factor, which stimulates endogenous bone marrow production, also prevented ovarian follicle loss in female mice undergoing chemotherapy. Another study explored the efficacy of freezing sperm stem cells from pre-pubertal boys undergoing chemotherapy and re-implanting them after treatment.
FI Branch-supported research also covers:
- The requirements of egg fertilization
- The effect of obesity on young girls' future fertility
- Proteins required for ovulation
- Growth and development of sperm
- Proteins involved in embryo implantation in the uterus
- Role of steroid receptor coactivator (SRC)-1 isoforms in the pathogenesis of endometriosis
- The safety and efficacy of medications to induce ovulation in women with PCOS
- Genetic causes of male and female infertility
- Formation and maturation of ovarian follicles and how they are maintained or lost over time
- Factors influencing egg quality
Research supported by the NICHD Pregnancy and Perinatology Branch (PPB) focuses on maternal health, pregnancy, fetal well-being, labor and delivery, and the developing child.
Other DER research supported by the Populations Dynamics Branch focuses on understanding changing patterns of family formation, including cohabitation, marriage, non-marital fertility, infertility, and low fertility.
Recent Institute advances in infertility research include the following:
- Identification of protein needed to establish pregnancy. Researchers discovered how the hormone progesterone suppresses the growth of the uterus's lining so that a fertilized egg can implant in the uterus. This key step occurs when a protein called Hand2 suppresses the chemical activity that stimulates growth of the uterine lining, also known as the uterine epithelium. The finding may contribute to understanding some forms of unexplained female infertility. The finding also has implications for understanding disorders in which growth of the uterine epithelium surges out of control, such as endometrial cancer or endometriosis, a disease in which endometrial tissue appears on the ovaries, bowel, or other tissues outside the uterus. Visit Researchers Identify Protein Essential for Embryo Implantation for more information.
- Discovery that autoimmunity to MATER protein may lead to POI. Researchers have discovered a way to slow the immune-system attack involved in a form of POI. In a mouse model, scientists found that the ovarian protein MATER, found in the mouse egg cell, is the main target of the autoimmune attack. Although MATER did not give complete disease protection, indicating that other factors play a role, scientists' success in slowing the immune attack provides hope for developing new treatments for POI eventually. Moreover, this study may someday lead to a way to identify women with a high risk for developing autoimmune POI before they actually lose ovarian function. These women may then be able to take advantage of fertility-sparing options such as freezing unfertilized eggs. See NIH Researchers Slow Immune Attack on Ovaries in Mice for more information.
- Evaluating zinc for healthy embryo development. In observations from egg cells of monkeys and mice, researchers found that an egg cell will steadily accumulate zinc atoms in the developmental stages leading up to fertilization. Fertilization in turn triggers a discharge of zinc. Researchers documented this discharge by bathing the egg in a solution that gives off light when exposed to zinc. The zinc discharge and accompanying light flash was referred to as a "zinc spark." These zinc sparks seem to lift the brakes on development and set the fertilized egg on the path to dividing and growing into an embryo. The study's authors suggest that zinc acts as a switch, turning off the process of cell division as the egg matures and turning it on again after fertilization. These findings demonstrate that zinc is essential for the development of a healthy egg and, ultimately, a healthy embryo. This research may lead to information that could be used for the treatment of infertility. See Zinc 'Sparks' Fly from Egg within Minutes of Fertilization for details.
- Identifying women at risk for preterm birth. Researchers analyzed data on birth outcomes of women who had been evaluated or treated for infertility, comparing them with outcomes of infertile women who were able to achieve pregnancy without treatment and with fertile women. The researchers limited their analyses to outcomes in women with singleton pregnancies—those leading to the birth of just one child—in women who had not previously given birth. The researchers found that the women who received infertility treatment were more likely to be somewhat older and obese, and they also were more likely to experience gestational diabetes and certain other pregnancy complications. The researchers did not find, however, that infertility treatment had elevated the risk of preterm birth, although it did seem to increase the risk of low weight of an infant at birth. They also found that women in all three groups who were giving birth to their first child were all at elevated risk of preterm birth, regardless of other factors. (PMID: 22633266)
- High levels of cadmium, lead linked to pregnancy delay. A recent study showed that higher blood levels of cadmium in females, and higher blood levels of lead in males, delayed pregnancy in couples trying to become pregnant. Females’ blood cadmium concentration was associated with a 22% reduction in the probability of pregnancy with each increase in the level of cadmium. Males’ blood lead exposure was associated with a 15% reduction in the probability of pregnancy for each increase in the level of blood lead concentrations. Cigarette smoke is the most common source of exposure to cadmium, a toxic metal found in the earth’s crust, which is used in batteries, pigments, metal coatings and plastics. Lead, a toxic metal also found in the earth’s crust, is used in a variety of products, such as ceramics, pipes, and batteries. Common sources of lead exposure in the United States include lead-based paint in older homes, lead-glazed pottery, contaminated soil, and contaminated drinking water.(PMID: 20933593)
Other Activities and Advances
The FI Branch supports several major research networks that address issues related to infertility, including:
The Reproductive Medicine Network (RMN) carries out large, multicenter clinical trials of diagnostic and therapeutic interventions for male and female infertility and reproductive diseases and disorders. Among other topics, the RMN conducts research on:
- Polycystic ovary syndrome
- Optimal conditions for in vitro fertilization
- Medications to stimulate ovulation in infertile women and factors that influence multiple pregnancies
- Ongoing monitoring of babies born in RMN clinical studies
Several tissue banks and information databases are supported by the NICHD Specialized Cooperative Centers Program in Reproduction and Infertility Research:
- The Human Endometrial Tissue and DNA Bank at the University of California, San Francisco contains information on genes associated with the uterus in humans, mice, pigs, sheep, goats, cows, and horses. The information is taken from published microarray data.
- The Ovary Bank at the University of California, San Diego
- A tissue bank of male reproductive tissues and fluids at Johns Hopkins University
- A tissue bank of nonhuman primate tissues at the Oregon National Primate Research Center
- The Ligand Assay & Analysis Core at the University of Virginia
- The Ovarian Kaleidoscope Database contains information regarding the biological function, expression pattern, and regulation of genes expressed in the ovary. It also provides information on gene sequences, chromosomal localization, human and murine mutation phenotypes, and biomedical publication links.
The PPB supports the following networks and studies to advance knowledge of the causes of pregnancy loss from miscarriage and stillbirth:
- The Stillbirth Collaborative Research Network (SCRN) was established to find the causes of stillbirth as well as ways to prevent or reduce its occurrence. SCRN studies also aim to understand any racial/ethnic factors that contribute to differences in stillbirth rates.
- The Prenatal Alcohol and Sudden Infant Death Syndrome and Stillbirth (PASS) Network aims to find ways of improving pregnancy outcomes and infant health. The PASS Network's key research program is the Safe Passage Study. Its purpose is to understand some of the causes of SIDS, stillbirth, and fetal alcohol spectrum disorders, especially those related to alcohol exposure during pregnancy.