The NICHD relies on several organizational units to study different aspects of contraception, from the biological mechanisms of different methods to the relevant decisions and behaviors of individuals and couples. The information below describes a few of these activities.
Institute Activities & Advances
Much of the Institute's research on contraceptive agents and their evaluation is done through the Contraceptive Discovery & Development Branch (CDDB). The Branch is the largest source of support for research on contraception within the federal government. It has responsibility for contraception research and development and for contraceptive and reproductive evaluation.
Using a combination of grants and contracts, the Branch supports and/or conducts the following activities:
- Phase I, II, III, or IV clinical trials to evaluate the safety and efficacy of new contraceptive methods for women and men
- Research to develop methods for male contraception, including hormonal and nonhormonal control of sperm production and/or sperm function
- Basic and translational contraceptive research and development that may lead to new hormonal or nonhormonal methods for inhibiting ovulation or fertilization
- Experimental studies in animals to determine the safety and efficacy of novel potential contraceptive agents
- Research to define optimal formulations and dosages of contraceptive agents, spermicidal microbicides, and therapies (in animals and humans)
- Epidemiologic studies, as appropriate, on contraception and on its relationship with other health issues, such as cancer
- Discussions of and reports and recommendations related to evidence-based contraception methods, including the Cochrane Collaboration and the World Health Organization
The CDDB addresses many of these research topics through cooperative agreements with research centers and research networks. These collaborative approaches are described in the Other Activities and Advances section.
The Institute's Population Dynamics Branch (PDB) funds studies of sexual behaviors and their relationship to disease prevention in a variety of populations. This includes basic and intervention research on the demographic, social, and behavioral aspects of the sexual transmission of HIV and other STDs. One focus of Branch-funded research is the interrelationships among pregnancy, pregnancy prevention, and HIV/STD prevention. An example of this interrelationship is the use of dual protection against unwanted pregnancy and infection.
At the Fertility and Infertility (FI) Branch, the mission is to alleviate infertility, discover new leads on contraceptives, and expand basic scientific knowledge about human reproduction. A current area of investigation is the use of certain hormonal contraception methods to treat reproductive and gynecological diseases.
The Section on Molecular Endocrinology (SME), part of the Institute's Division of Intramural Research (DIR), investigates the molecular basis of peptide hormone control of gonadal function, with particular emphasis on the structure and regulation of the luteinizing hormone and prolactin (PRL) receptor (PRLR) genes, concentrating studies on the function and regulation of gonadotropin-regulated testicular RNA helicase (GRTH/DDX25), an essential posttranscriptional regulator of spermatogenesis that was discovered, cloned, and characterized in their laboratory. The various functions of GRTH/DDX25 provide fertile ground for the development of a male contraceptive.
Other Activities & Advances
- In 1996, the NICHD established the Contraceptive Clinical Trials Network (CCTN) to conduct clinical trials of new contraceptive drugs and devices. The CCTN is funded through the CRH Branch and includes 12 sites for clinical evaluation of new female contraceptives and two sites for evaluating male contraceptives. Sites are chosen based on their capacity to conduct Phase I, II, and III trials for contraceptive drugs and devices. CCTN research includes studies of:
- The ability of progestin- and testosterone-based topical gels to reduce gonadotropin levels and reversibly inhibit sperm production in order to provide effective, user-controlled hormonal contraception for men
- A progesterone receptor modulator, CDB-2914, as an emergency oral contraceptive when taken within 72 hours of unprotected intercourse
- The contraceptive effectiveness of new agents that can be used as a spermicidal vaginal gel either alone or in combination with a diaphragm
- The efficacy of a new female condom for preventing both pregnancy and STDs
- Progestin-based compounds that can prevent pregnancy without increasing the risk of blood clots and other venous thromboembolism-type conditions, especially in obese women
- Contraceptive effectiveness of a new vaginal ring that can be used for 13 cycles. The device releases a combination of ethinyl estradiol and a new progestin and the ring is used in a regimen of 3 weeks in and 1 week out for a full year of contraceptive use.
- The use of a novel progestin- and estradiol-releasing vaginal ring for effective contraception without increasing the risk of blood clots and other venous thromboembolism-type conditions, especially in obese women
- Creation of the Contraceptive Development Research Center Program (CDRCP) was mandated by Congress in 1993. Legislation passed that year directed the NICHD to fund contraceptive research centers and to focus the efforts of these centers on research that might lead to new contraceptive products. The program is supported through the Institute's CDDB and currently includes four centers. Individual projects focus on basic, preclinical, or clinical research, or on a combination of these areas. The CDRCP also serves as a national resource for supporting the career development of young scientists who elect to pursue research in fertility regulation. CDRCP research topics include:
- Hormonal suppression of the hypothalamic-pituitary-gonadal axis in men or women
- Development of novel vaginal delivery systems for drugs that inhibit ovulation
- Analysis of paracrine regulation of oocyte development by cumulus cells and mechanism of factors regulating follicular development and follicular rupture
- Novel delivery methods for contraceptive agents
- Dual-use compounds that protect against sexually transmitted infections and pregnancy for women
- Translational research aimed at product identification and optimization for male contraception
- Nonhormonal methods of ovulation inhibition for contraception
- Integrated computational modeling, biological screening, structure biology, and medicinal chemistry for structure-based drug discovery
- Funded through the CDDB Branch, the Male Contraceptive Development Program (MCDP) conducts a wide range of research with the ultimate goal of developing useful contraceptive products for men. Research focuses for the program include studies on:
- Mechanisms regulating how spermiogenesis might be targeted by novel male contraceptives
- Signaling pathways for the protein receptor c-Ros in male fertility
- Sperm glycolytic enzymes
- Nonhormonal targets for male contraception, including the tight junctions between Sertoli cells and germ cells, which are required for appropriate cell-cell interactions during sperm development (spermatogenesis)
- Injectable formulation of Acyline, a potent gonadotropin-releasing hormone antagonist, to assess drug safety and ability to suppress spermatogenesis
- Novel male contraceptives, including H2-gamendazole, an orally active anti-spermatogenic compound
- Pharmaceutical targeting of a sperm-specific calcium cation channel (CatSper) and consequences of targeting on male fertility
- The National Centers for Translational Research in Reproduction and Infertility (NCTRI) (Formerly the Specialized Cooperative Centers Program in Reproduction and Infertility Research [SCCPIR]) is a national network of research-based centers promoting multidisciplinary interactions between basic and clinical scientists working on translational research programs in the reproductive sciences.” The first SCCPRIR request for applications was issued in 1996, and the first four awards were issued in 1998. The program now includes 14 sites around the country and is supported by the NICHD branch on Fertility & Infertility (FI). The centers focus on reproductive:
- Developmental biology
- Tract biology and physiology
- Endocrinology and neuroendocrinology
- Genetics and epigenetics
- One of the sites, the Center for Research in Reproduction Ligand Assay & Analysis Core at the University of Virginia, employs state-of-the-art methods to quantitate peptide and steroid reproductive hormones in blood and tissue. It also develops new methodology; prepares labeled reagents for immunoassays, immunocytochemistry, and binding studies; and assists in the transfer of technology to participating investigators.