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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Suggested Citation:"1 Introduction." Institute of Medicine. 2004. New Frontiers in Contraceptive Research: A Blueprint for Action. Washington, DC: The National Academies Press. doi: 10.17226/10905.
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Introduction Family planning is a socially beneficial activity that affects the well- being of women, men, children, families, and society as a whole. The ben- efits of planned fertility include the more effective intergenerational trans- fer of resources, resulting in improved child health and development (Lee, 2003~; increased longevity and empowerment of women, with the atten- dant economic benefits to the family and the community; and a reduced lifetime risk of chronic illness or death from a pregnancy-related condi- tion. Contraception, when practiced with barrier methods, also lessens the likelihood of sexually transmitted diseases. By consciously practicing family planning, couples can choose to contribute to the overall health, stability, and economy of their families and their communities. Conversely, the consequences of unintended pregnancy are quite serious, imposing significant burdens on children, women, men, and families (reviewed by the Institute of Medicine, 1995~. The child born from an unplanned conception is at greater risk of low birth weight, dying in its first year of life, being abused, and not receiving sufficient resources for healthy development. An unplanned conception also exposes women to the usual health risks of pregnancy, which can include maternal death. Closely spaced births pose additional risks for the mother and child. In a study that controlled for socioeconomic and demographic differences, it was found that women who spaced childbearing at 27- to 32-month inter- vals were 2.5 times more likely to survive childbirth than women who gave birth at 9- to 14-month intervals. Children born 3 to 4 years after a previous birth were found to be 2.3 times more likely to survive the first year of life than children born less than 2 years after a previous birth 17

8 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH (Rinehart et al., 2002~. When a pregnancy is unplanned, the mother also has a greater risk of depression and of being physically abused, and her relationship with her partner is at greater risk of dissolution. Both the mother and the father of the child may suffer economic hardship and may fail to achieve their educational and career goals. Given these issues, a woman experiencing an unintended pregnancy may also face the deci- sion to have an abortion. Unintended pregnancy is frequent and widespread in the United States (Institute of Medicine, 1995) and the world (Global Health Council, 2002~. In the United States, about half of all pregnancies are unintended at the time of conception (Henshaw, 1998; Institute of Medicine, 1995~. According to a recent analysis by the Global Health Council, the world's 1.3 billion women between the ages of 15 and 45 experienced more than 1.2 billion pregnancies in the 6 years between 1995 and 2000.~ Of these, more than 300 million or more than one-quarter were unintended. Unintended pregnancy affects all segments of society it is not just a prob- lem of teenagers or unmarried women, poor women or minorities, or women living in the developing world. For example, a survey of more than 14,000 French households revealed that 33 percent of pregnancies occurring over a 5-year period were unplanned, half of which were terminated by abortion. Sixty-five percent of the unplanned pregnancies occurred among women using contraception (Bajos et al., 2003~. A survey in the United States found that 50 percent of unintended pregnancies occurred among couples using some form of contraception (Henshaw, 1998~. Poor women in developing countries bear the greatest burden with regard to maternal mortality and morbidity due to unplanned preg- nancies. The lifetime risk of dying during pregnancy and childbirth in these countries is several hundred times higher than that in wealthier nations (1 in 4,000 in North America and Europe versus 1 in 15 in Africa). Maternal mortality is highest in countries where women are least likely to have access to modern contraceptive services (Global Health Council, 2002~. In Burkina Faso, where only 4 percent of women use family plan- ning methods, 1 in 14 will die of maternal causes over the course of her iThe Global Health Council compiled a country-by-country profile of all 227 countries in the world, based on the best available statistics from the U.S. Census Bureau, United Nations agencies, country reports, and specialized surveys carried out by a variety of respected research organizations. For each country and each year, data were generated on the number of pregnancies that occurred, the number that ended in miscarriages and abortions, and the number carried to term. For each of these, the data sources were used to assess the number that resulted from unintended pregnancies and the number of unintended pregnancies that resulted in the death of the mother.

INTRODUCTION 19 lifetime. In Brazil, the opposite is true; nearly three-quarters of the female population regularly use family planning services, and their lifetime risk of maternal mortality is considerably lower: 1 in 130 (Global Health Council, 2002~. In Russia, abortion has long been the traditional method of family planning (Gadasina, 1997), and Russia has the highest abortion rate in the world.2 Although pregnancy terminations are freely available, contraception is not. Nonetheless, even with the easy availability of abor- tion services, an estimated 15 percent of procedures are performed in illegal private facilities. The lack of contraceptive choices has resulted in excess maternal mortality nearly one-third of maternal deaths in Russia are estimated to be due to abortion procedures and an explosion in sexually transmitted infections (Karelova, 1999; Parfitt, 2003~. Although the number of live births has stabilized at about 131 million per year worldwide, the number of women dying each year as a result of unintended pregnancy has increased since 1995. Over the 6 years exam- ined, nearly 700,000 women died as a result of unintended pregnancies. Although more than one-third died from problems associated with preg- nancy, labor, and delivery, the majority more than 400,000 died as a result of complications resulting from abortions carried out under unsafe and often illegal conditions. An unintended pregnancy often leads to the decision to have an abortion. Furthermore, for every maternal death, an estimated 30 additional women suffer pregnancy-related health problems that are frequently permanently debilitating (Global Health Council, 2002~. The death of a mother is emotionally, socially, and economically destructive to families and communities (Global Health Council, 2002~. In developing nations, where an estimated 98 percent of pregnancy-related deaths take place, the loss of a mother translates into the increased likeli- hood that surviving family members will not be able to properly care for existing children, and such children have a much greater risk of dying themselves (Steiner et al., 2000~. Moreover, because these women typi- cally die between the ages of 15 and 45, elevated rates of maternal mortal- ity represent a significant threat to the broader socioeconomic systems (reviewed by the Global Health Council, 2002~. CONTRACEPTIVE USE Contraceptive use in developing countries has increased greatly since the 1960s and in many cases is now approaching the levels observed in 2See The Library of Congress Country Studies, 1996, available online at http://www. lupinfo.com/country-guide-study/russia/russia65.html (accessed October 2003~.

20 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH developed countries (overall rates of use, 60 and 70 percent of couples, respectively). Worldwide, more than 580 million women use modern methods of contraception (Figure 1.1), contributing to a large drop in the total fertility rate in developing countries (United Nations Development Programme, 2003; United Nations Population Fund, 2001; World Bank, 2003; World Health Organization, 2003~. The trend is notable not only for its demographic impact but also for its ability to free women to pursue a productive life in addition to a reproductive life. However, studies show that more than 120 million people around the world do not use any form of contraception, even though they report that they are sexually active and do not wish to become pregnant (Figure 1.1~. Although a number of effective reversible and nonreversible contra- ceptive methods exist (barrier methods, hormonal methods, intrauterine devices, and contraceptive sterilization), all have shortcomings in the form of failure rates and undesirable side effects that lead to the discontinua- tion of reversible methods. WHO's recent warnings against the use of spermicides by women at high risk of HIV infection may lead to further reduction in the use of barrier methods. The effectiveness of many contra- ceptives depends on correct and consistent use, which can be difficult for people to achieve (Trussell and Stewart, 1998~. Indeed, U.S. women and their partners relying on reversible means of contraception and those using no contraception contribute roughly equally to the pool of unintended pregnancies. In the United States, the 7 percent of women who are at risk for unintended pregnancy and who use no method of contraception account for about half of all unintended pregnancies that occur each year (Henshaw,1998~. The remaining 50 percent of all unintended pregnancies occurred among 93 percent of at-risk U.S. couples practicing some form of contraception, partly reflecting the inconsistent use of effective methods. The same pattern is true in other developed countries (Bajos et al., 2003; Darroch et al., 2001~. In addition, most currently available methods have discontinuation rates approaching 50 percent after 1 year of use, usually because of side effects (Rosenberg et al., 1995; Trussell and Vaughan, l999~. When women discontinue highly effective methods, they usually choose a less effective method. For example, one study showed that 70 percent of women who discontinue oral contraceptives begin using a less effective method, and 20 percent use no contraceptive method at all (Rosenberg et al., 1995~. Moreover, women who continue using a method often do so despite the 3See http: / /www.who.int/reproductive-health/family_planning/updates.html (accessed November 2003~.

INTRODUCTION 1,800 - 1,500 - 1,200- 600 O- 21 Contraceptive use and need (Year 2000) Total 1,047 ~ Marital status1 ...................... MARRIED ................. using contraception -648 million 582 Women of Married women Unmarried Users of reproductive of reproductive women of modern age age reproductive methods age . ,,, ~ ,................................. PiPi - | UNKNOWN | .... 1 ..... 1 | need I UNMET l need . l . ~ 1 7632 i ! ~ . t::::::::::::::::::::::::. ::::: 23 i Usersof Non-users, No information traditional sexually active methods FIGURE 1.1 Contraceptive use and need worldwide. Traditional methods include withdrawal, periodic abstinence, and other non-supply-related methods. Modern methods include hormonal contraceptives and barrier methods such as dia- phragms, condoms, and intrauterine devices. Column 1: Total number of women of reproductive age (15-49) is 1.553 billion in the year 2000 (Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, 2003~. Column 2: Total number of women of reproductive age (15-49) married or in union is 1.047 billion (Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, 2002~. Column 3: Unmarried women of reproductive age number 506 million (sub- tracting Column 2 from Column 1~. This figure is included because we know very little about the needs of these women and if or how they are being met. Some of them are sexually active and using contraceptive methods, some are sexually active and are not using any method of family planning, some may wish to con- ceive, and some are not sexually active. Columns 4 and 5: Married women using contraceptive methods, separated ac- cording to "modern" and "traditional" (Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, 2002~. Column 6: 123 million: Unmet need as defined by the number of women wish- ing to space or limit births but not currently using a method of contraception. This number includes married and unmarried women in developing countries (exclud- ing China) and the former Soviet Union, but not the West and so is probably an underestimation. Numbers in other columns are world-wide (Ross and Winfrey International Family Planning perspectives, 2002~. Column 7: Use and needs for 782 million women are unaccounted for in the graph (subtract Columns 4, 5, and 6 from Column 1~. Their needs may be met, unmet, or unknown, depending on their sexual activity and desire for pregnancy.

22 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH presence of unwanted side effects, which they tolerate in return for preg- nancy prevention. Thus, continuation rates are not a surrogate for accept- ability (Severy, 1999; Severy and Thapa, 1994~. The cultural, personal, or political unacceptability of the various methods also can contribute to a lack of contraceptive use. Access to effective methods may also be quite limited for many seg- ments of society, especially those in developing countries with inadequate resources for health care. Beginning in 1998, 20 U.S. states have required that health insurers cover all contraceptives approved by the FDA (Alan Guttmacher Institute, 2003~. However, at the federal level, legislation in- troduced in 1997, 1999, and 2001 to mandate such coverage was never brought to a vote. Further, an estimated 43.6 million people lacked health insurance for all of 2002 (U.S. Department of Commerce, 2003) and none of these people would have benefited from a mandated coverage of con- traception by health insurers. Even if total contraceptive prevalence were to remain the same, the need for access to effective contraceptive methods will continue to rise as increasing numbers of people worldwide attain reproductive age. World- wide, about 60 percent of couples at risk for pregnancy use contracep- tives, but in some developing countries, the rates of contraceptive use are much lower. Countries in sub-Saharan Africa, for example, have contra- ceptive use rates of only about 20 percent.4 Although the population growth rate is slowing and in fact has become negative in a number of Western countries, the population of the world as a whole continues to rise, particularly in developing countries. As a result, during the next decade, 600 million girls will become adolescents, which will be the largest cohort of young women in human history (Global Health Council, 2002~. Because these young women will be from diverse backgrounds, there will be an urgent need for a larger variety of contraceptive methods. More- over, it is now well appreciated that there is no "perfect" contraceptive because the contraception needs of women and men change over the reproductive and family life cycles. Methods are needed for child spacing as well as permanent pregnancy prevention, for adolescents as well as those approaching menopause, for postpartum and breast-feeding women, for women and men with medical conditions that restrict the con- traceptive that they can use, for men and women with few resources, and for men and women whose personal situations make correct and consis- tent use difficult. In addition, the development of new dual protection methods those that protect against pregnancy as well as against HIV/ AIDS and other sexually transmitted infections would be highly benefi- 4According to 2002 data of the United Nations Population Division.

INTRODUCTION 23 cial, since the HIV/AIDS pandemic threatens world health and continues to devastate sub-Saharan Africa and Asia. Clearly, there is an enormous unmet need for effective and acceptable family planning worldwide. For many men, women, children, families, and communities, the negative con- sequences of not meeting family planning needs are high. Cost, accessibility, and consistent and correct use of existing methods still present enormous challenges to international family planning efforts in particular. Although there is value in improving the characteristics and means of delivery of current methods, there is also urgency in proceeding with new research on and the development of new methods to meet the range of contraceptive needs throughout the world and across the human life span. The usual time line from basic research through target identifi- cation and then to product introduction of 10 to 14 years means that an effort initiated today would barely be on track to meet the aforementioned contraception needs of the coming decade. The development of new contraceptives that increase the range of options available to women and men worldwide would improve the lives of families everywhere. In 1996, the Institute of Medicine (1996) issued its most recent of several reports assessing the state of contraceptive research and develop- ment. That report exposed and analyzed the reasons for the apparent lack of activity and progress in the field since the first "contraceptive revolu- tion," which began in the 1950s and 1960s, when most of the current contraceptive methods were initially developed (Institute of Medicine, 1996~. Many of the recommendations put forth in that report are as rel- evant today as they were in 1996, but the recent unprecedented advances in science and technology warrant a fresh examination of the research goals and agenda in field of contraception. Although progress has been made in the intervening years, contraceptive modalities recently developed or in- troduced are mainly variations on preexisting approaches. Furthermore, progress in some areas thought to be promising in 1996 (e.g., immuno- contraception) has been minimal, whereas new discoveries point to prom- ising new opportunities. Moreover, there is still a great need to reenergize the field and to translate significant observations from the science of re- productive biology to practical application in fertility regulation. Many barriers remain, but the progress that has been made is evidence that they can be surmounted with committed resources and hard work. COMMITTEE CHARGE The current IOM committee was charged with recommending priority areas for future research and development in the field of contraception. To accomplish that goal, the committee assumed three main tasks in this study:

24 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH · In basic science, to identify opportunities derived from recent advances in biomedical research. · In the product development process, to propose new strategies and frameworks for contraceptive development. · In implementation, to describe the resources, infrastructure, and coordination needed to achieve success. With respect to science, revolutionary changes have occurred in basic biomedical research, materials sciences, and drug delivery since publica- tion of the 1996 IOM report. The advances in biomedical research have provided exciting new opportunities for studying the basic biology of reproduction, which could in turn lead to the discovery of new targets for contraception. In particular, the tools and technologies of genomics, proteomics, lipidomics, and glycomics have great potential for identify- ing targets that could facilitate the development of radically new ap- proaches to contraception. Novel approaches for the development and delivery of drugs and other products could also provide new insights into ways to create innovative contraceptives once potential targets have been identified. Despite these advances, however, there has been flagging interest in contraceptive development not only in the pharmaceutical industry but also in the broader scientific community that must be revived if these innovations are to generate products that satisfy the demand for safe, effective, and convenient contraceptives. Regarding the product development process, many obstacles to con- traceptive development were identified in past IOM reports, particularly the 1996 report, and many continue to plague the field. However, new paradigms for science, including large-scale science, have emerged in the past few years, along with new models for public-private collaboration. In terms of implementation, new parties are interested in the process of contraceptive development and dissemination, and new global con- sortia are also dealing with reproductive health. These new participants offer unique opportunities to move contraceptive development forward if there is an expansion of the number and the breadth of expertise of scien- tists and clinicians dedicated to contraceptive research and development. Those who are active in the field are nearing retirement, with prospects for new blood seemingly bleak without a widespread commitment to and enthusiasm about contraceptive research and development. A major chal- lenge is to identify, attract, train, and support the career development of individuals who have an appreciation for the multidisciplinary issues sur- rounding fertility regulation. This will require a significant departure from the current ways in which investigators are trained as well as a special- ized environment for carrying out research in this area. These topics will be addressed in greater detail in the remaining chapters of this report.

INTRODUCTION 25 FRAMEWORK OF THE REPORT Chapter 2 provides an overview of technological advances that have revolutionized the fields of biomedical research, drug discovery, and drug development and that could thus have a tremendous impact on contra- ceptive research and development. The committee examines ways in which the new methods can be used to identify and validate targets before drug development. Chapter 3 describes the challenges associated with product identi- fication and development, once potential new targets for contraceptive development have been identified, and suggests a variety of approaches to stimulate and speed progress in translational research and drug development. Chapter 4 examines the role of the social and behavioral sciences in shaping the pursuit of leads that are likely to find a receptive set of users and that are appropriate to particular populations or circumstances. This chapter also examines ways to improve the use and acceptability of cur- rent and new contraceptives, such as enhancing and promoting other health benefits beyond pregnancy prevention. Chapter 5 delineates a variety of strategies that can be used to capital- ize on advances in science and technology and to overcome remaining obstacles to progress in contraceptive research and development. Because of the important role of the 1996 IOM report Contraceptive Research and Development: Looking to the Future as a foundation for the committee's work, an update on developments that have occurred since that report was published is included in Appendix A. The agenda for and participants in the committee's workshop are provided in Appendix B. and a short biography of each member of the committee is presented in Appendix C. REFERENCES Alan Guttmacher Institute. 2003. State Policies in Brief: Insurance Coverage of Contraceptives. [Online]. Available: http://www.agi-usa.org/pubs/spib_ICC.pdf [accessed Novem- ber 2003]. Bajos N. Leridon H. Goulard H. Oustry P. Job-Spira N.2003. Contraception: from accessibil- ity to efficiency. Hum Reprod 18~5~:994-999. Darroch JE, Singh S. Frost JJ.2001. Differences in teenage pregnancy rates among five devel- oped countries: the roles of sexual activity and contraceptive use. Fam Plann Perspect 33(6):244-250, 281. Gadasina A. 1997. Struggling to survive in Russia. Plan Parent Chall (1-2):40-42. Global Health Council. 2002. Promises to Keep: The Toll of Unintended Pregnancies on Women's Lives in the Developing World. Washington, DC: Global Health Council. Henshaw SK.1998. Unintended pregnancy in the United States. Fam Plann Perspect 30(1):24- 29, 46.

26 NEW FRONTIERS IN CONTRACEPTIVE RESEARCH Institute of Medicine. 1995. The Best Intentions: Unintended Pregnancy and the Well-Being of Children and Families. Brown S. Eisenberg L, eds. Washington, DC: National Academy Press. Institute of Medicine. 1996. Contraceptive Research and Development: Looking to the Future. Harrison PF, Rosenfield A, eds. Washington, DC: National Academy Press. Karelova GN. 1999. A reduction of abortions. Russian Federation. The Hague Forum. Integration (60~:29. Lee RD. 2003. Rethinking the evolutionary theory of aging: transfers, not births, shape senescence in social species. Proc Natl Acad Sci U S A 100~16~:9637-9642. Parfitt T. 2003. Russia moves to curb abortion rates. Lancet 362~9388~:968. Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat. 2002. World Contraceptive Use, 2001. New York: United Nations. Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat. 2003. World Population Prospects: The 2002 Revision. New York: United Na- tions. [Online]. Available: http://www.unpopulation.org/ [accessed December 2003]. Rinehart W. Compton AW, Rigby HM. 2002. Three to Five Saves Lives. Population Reports 30~3~:1. Rosenberg MJ, Waugh MS, Meehan TE. 1995. Use and misuse of oral contraceptives: risk indicators for poor pill taking and discontinuation. Contraception 51~5~:283-288. Ross JA, Winfrey WL. 2002. Unmet need for contraception in the developing world and the former Soviet Union: an updated estimate. International Family Planning Perspectives 28(3):138-143. Severy LJ. 1999. Acceptability as a critical component of clinical trials. Adv Pop 3:103-122. Severy LJ, Thapa S.1994. Preferences and tolerance as determinants of contraceptive accept- ability. Adv Pop 2:119-139. Steiner MJ, Taylor DJ, Feldblum PJ, Wheeless AJ. 2000. How well do male latex condoms work? Pregnancy outcome during one menstrual cycle of use. Contraception 62~6~:315- 319. Trussell J. Stewart F. 1998. Contraceptive efficacy. In: Hatcher RA, Trussell J. Stewart F. Cates W. Stewart GK, Guest F. Kowal D. Contraceptive Technology. 17th rev. ed. New York: Ardent Media. Trussell J. Vaughan B. 1999. Contraceptive failure, method-related discontinuation and resumption of use: results from the 1995 National Survey of Family Growth. Fam Plann Perspect 31~2~:64-72, 93. United Nations Development Programme.2003. Human Development Report 2003: Millennium Development Goals: A Compact among Nations to End Human Poverty. [Online]. Available: http: / /hdr.undp.org/reports /view_reports.cfm?year=2003 [accessed August 2003]. United Nations Population Fund. 2001. Annual Report 2001. [Online]. Available: http:// www.unfpa.org/about/report/2001/index.htm [accessed August 2003]. U.S. Department of Commerce, U.S. Census Bureau. 2003. Health Insurance Coverage in the United States 2002. [Online]. Available: http: / /www.census.gov/prod/2003pubs/ p60-223.pdf [accessed November 2003]. World Bank.2003. World Development Report 2003: Sustainable Development in a Dynamic World. [Online]. Available: http: / /econ.worldbank.org/wdr/wdr2003/ [accessed August 2003]. World Health Organization.2003. The World Health Report 2002. [Online]. Available: http:// www.who.int/whr/en/ [accessed August 2003]. 1 ~

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More than a quarter of pregnancies worldwide are unintended. Between 1995 and 2000, nearly 700,000 women died and many more experienced illness, injury, and disability as a result of unintended pregnancy. Children born from unplanned conception are at greater risk of low birth weight, of being abused, and of not receiving sufficient resources for healthy development. A wider range of contraceptive options is needed to address the changing needs of the populations of the world across the reproductive life cycle, but this unmet need has not been a major priority of the research community and pharmaceutical industry. New Frontiers in Contraceptive Research: A Blueprint for Action, a new report from the Institute of Medicine of the National Academies, identifies priority areas for research to develop new contraceptives. The report highlights new technologies and approaches to biomedical research, including genomics and proteomics, which hold particular promise for developing new products. It also identifies impediments to drug development that must be addressed. Research sponsors, both public and private, will find topics of interest among the recommendations, which are diverse but interconnected and important for improving the range of contraceptive products, their efficacy, and their acceptability.

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