The National Institute of Environmental Health Sciences (NIEHS) is most pleased to co-sponsor this supplement issue on the state of research advancing knowledge of human reproduction at the global and individual public health levels. These two views capture the full range of importance of reproduction to our species — the quantitative impact of global population growth demands and the qualitative desires of the human family. The NIEHS is the principal federal agency in the United States of America for research and research training on the effects of environmental agents on human health. The mission of NIEHS is to develop knowledge that will permit the better management of risks associated with body exposures to or processing of environmental factors or agents. Within this mission, the NIEHS supports major efforts in systems toxicology research focused on the reproductive and developmental sciences investigating the effects of chemical, physical and biological environmental agents on human health and wellbeing. NIEHS is committed to advancing knowledge for environmental medicine and equipping clinicians with the right tools to prevent, attenuate or ameliorate human diseases; contributing sound data to environmental regulatory and public health policy issues; and stimulating debate on controversial ethical issues involved in the environmental health sciences.

Population and the environment will become the major public health issue of the foreseeable future as humankind continues its unrelenting alteration of the environment in which the species Homo sapiens faces the forces of natural selection in its effort to survive. While we humans do not often contemplate our survival as a species, nature has a way of "shoving it your face" at critical junctures in the evolution of the environment supporting the niche in which a species is resident for a brief period in the hundreds of millions of years of the evolutionary time timescale. While an innate skill at adaptation has endowed Homo sapiens with evolutionary success to date, for how much longer will this "career success" path endure? At the core of sustainable human development as a population, in terms of the environment, is the "carrying capacity" of the earth�s thin biosphere in which we are allowed, by nature, to exist and, by our fellow humans, to pollute. At the core of the "survival of the species" is the "reproductive capacity" of the human species, its impacts on the environment, and the environments� impact on it. Mankind partnered with Womankind has established a wonderfully successful "reproductive strategy" to ensure the survival of the species and it has utilized to the fullest the genetic plasticity of the human genome in meeting the challenges of evolutionary survival. We are, however, at an the amazing point in human history where functional knowledge of genomics, population genetics, medical genetics, and molecular biology can be applied to iatrogenically direct our "reproductive strategy" as a species outside the laws of randomness imposed by nature over all the millions of "natural selection" years that preceded the present day. We have in our hands a human-made "genomic toolbox" containing the molecular tools necessary to craft changes in the human genome that direct our evolutionary future. When all is finally reduced to a practical equation in this regard, gene-environment interaction is the motivational mechanism molding our genomic plasticity and the guiding hand in Rodin�s famous sculpture of genesis, molding from clay the sexually dimorphic human male and female for procreation purposes, may have become that, of humanity, not nature.

What we are being "exposed" to as a population, in terms of biological effector agents, drives the adaptation mechanism within our human population. As it has been sagely said, "genetics is the smoking gun, but the environment is the trigger." Human kind has advanced intellectually enough to understand nature�s harsh penalties that are inflicted by environmental factors, including toxicants and toxins, through genotoxic and epigenotoxic effects on our population�s gene-pooled genome. We do not need to look to the future for these penalties or the desire to "dodge bullets" being fired at our collective and individual genome. We are already in the midst of recognized public health issues that arise from adverse environmental agent exposures that differentially affect members of our human population, including the gonadal and embryo-fetal basis of adult and trans-generational disease expression. These public health issues are the basis of NIEHS Environmental Health Sciences research that seeks to identify related morbidity/mortality mechanisms, develop "sound science for sound decisions" to underpin risk assessment for national health regulatory policy and implement public health intervention and prevention strategies to benefit the public health of our species. For more information, please visit NIEHS on the Internet, at http://www.niehs.nih.gov. Information on available research project support can be found at the Division of Extramural Research and Training website at: http://www.niehs.nih.gov/dert/ programs/special/repro.html. A wealth of information on the research programs of the NIEHS� National Toxicology Programs (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR), including authoritative national and international reports, reviews and summaries of research findings involving global and individual adverse effects on human reproduction and development, may be found at: http://cerhr.niehs.nih.gov/.

The UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP) (http://www.who.int/reproductivehealth/) is pleased to sponsor this supplement, which so vividly documents the contribution of modern science to the regulation of human fertility.

In 1972, the World Health Organization (WHO) created HRP to coordinate, promote, conduct, and evaluate international research in human reproduction. Sixteen years later, the United Nations Development Programme (UNDP), the United Nations Population Fund (UNFPA), and the World Bank decided to join WHO in sponsoring the programme, making it the main instrument within the United Nations system for research in human reproduction.

Around the time HRP came into being, the global international health and development agenda was dominated by rapid population growth and the need to control fertility. Today, the focus has turned to poverty, demographic and epidemiological transitions, and the impact of HIV/AIDS. This evolution reflects not only changing realities but also the fact that we have been remarkably successful in providing people with the wherewithal to manage their fertility. In the last three decades, contraceptive prevalence has risen more than sixfold in developing countries and fertility has fallen in almost every corner of the world.

But the job—that of HRP and its partners—is far from finished: there are still an estimated 350 million couples of reproductive age—over a third of the world�s total—who cannot find a contraceptive method that meets their requirements. And there are still concerns about the safety and efficacy of some family planning methods. Also, some 10% of couples worldwide are unable to achieve the desired size of their family as a result of primary or secondary infertility.

In the two decades following its creation, HRP devoted much of its energies to addressing the basic right of couples to have the number of children they want when they want. This work produced two new once-monthly injectable contraceptives currently marketed in more than 40 countries. HRP has also played a pioneering role in emergency contraception, notably in confirming the effectiveness of the progestin levonorgestrel and in making it easier and safer to use. Today, women in more than 80 countries are using it as a "second chance" contraceptive option following unprotected intercourse.

Mifepristone, too, has been the subject of several HRP-supported studies over the past decade that together have contributed to the development of regimens combining mifepristone and a prostaglandin for non-surgical termination of pregnancy and to the use of very low doses of mifepristone for emergency contraception.

In addition, long-term clinical trials on copper-releasing IUDs, funded by HRP and involving many thousands of women in a dozen countries, have over the years progressively extended the recommended length of time women can safely keep these devices in place—from one or two years in the early 1970s to ten years today, and possibly longer if the promise of ongoing trials holds up. HRP has also made seminal contributions to other areas related to the safety of contraceptive methods, such as the risks of cancer and cardiovascular diseases in women using hormonal contraception, and the risks and benefits of Norplant^®, the levonorgestrel-releasing implant, to mention only three areas.

HRP, originally created to bring new energy, funding, and a revitalized sense of purpose into research on fertility regulation, has in recent years brought its research expertise to bear on areas of sexual and reproductive health where knowledge is inadequate and the burden of ill-health depressingly heavy. Today, for example, reproductive ill-health accounts for some 22% of the total burden of disease in women aged 15–44 years. Every year, more than half a million women die during pregnancy or delivery, or as a result of a postpartum complication—99% of them in developing countries and 12% of them, or 60 000, adolescents. About 20 million women undergo unsafe abortions each year, resulting in some 80 000 deaths annually. An estimated 2 million women are living with invasive cervical cancer and 450 000 new cases are diagnosed each year. And in 2001, 5 million people became infected with HIV, among them 800 000 children under 15.

HRP is particularly well placed to extend the boundaries of knowledge in these other areas of sexual and reproductive health. Today, its global research network comprises more than 120 research institutions in nearly a third of the world�s countries. Thanks to that network, HRP can provide data on human reproduction that are pertinent to people living in the most diverse circumstances and cultures. HIV/AIDS, in particular, is an area of research where HRP can justifiably claim a comparative advantage, since many of the interventions needed to prevent the spread of this epidemic can only be delivered through sexual and reproductive health services, including those devoted to family planning.

The CONRAD Program is proud to be sponsor of this effort to assemble and make more available the current literature on scientific, medical, and social issues concerning fertility.

CONRAD is dedicated to improving reproductive health worldwide by expanding the contraceptive choices for women and men and helping to prevent the transmission of HIV and other sexually transmitted pathogens. Established in 1986 under a cooperative agreement with the U.S. Agency for International Development and the Eastern Virginia Medical School, CONRAD supports innovative research and helps move promising leads through clinical trials for safety and effectiveness. Assistance can be in the form of financial or technical support for preclinical and clinical research and product development.

Research efforts are directed toward methods that would be suitable for use in developing countries. Among the most promising projects are chemical barriers that would protect women from pregnancy and/or infection with HIV and other sexually transmitted pathogens. Expanded safety studies are either planned or underway for several of these products and effectiveness studies are in development. CONRAD has also supplied the developers of two intravaginal devices, Lea's Shield^® and FemCap^TM, with clinical data for inclusion in their respective regulatory approval applications, and is supporting development of two other intravaginal devices and two female condoms. Among the male approaches, those that hold the most promise are androgen/progestin combinations. Dose-finding and contraceptive effectiveness studies are underway to explore this approach.

Additional assistance is offered through two subprojects of CONRAD. Supported with funding from a number of private foundations, the Consortium for Industrial Collaboration in Contraceptive Research (CICCR) was established in 1995 to help revitalize the commitment of industry to developing new contraceptive products. Established in 2000 with funding from the Bill & Melinda Gates Foundation, the Global Microbicide Project (GMP) offers support specifically for research and development of chemical barriers to prevent women from HIV and other sexually transmitted pathogens.

Researchers and developers interested in learning more about funding opportunities and assistance can visit the CONRAD Web site at www.conrad.org.

The Reproductive Sciences Branch (RSB) of the National Institute of Child Health and Human Development is the principal funding unit within NIH that provides support to extramural investigators for research and research training activities on all biological aspects of human and relevant animal reproduction. The mission of the RSB is to encourage and support scientific research aimed at alleviating human infertility and reproductive disorders, uncovering new contraceptive leads and expanding our fundamental knowledge of the processes underlying the success or failure of human reproduction. To achieve its mission, the RSB supports a comprehensive program of research funding, providing research funds for basic, clinical and translational studies aimed at increasing our understanding of normal reproduction and reproductive pathophysiology.

The Contraception and Reproductive Health Branch (CRHB) develops and supports research and research training programs in reproductive health, epidemiology and contraceptive technology, including developing and evaluating new contraceptive methods; determining the mechanism of action and medical effects of contraceptive and reproductive hormones, drugs, devices and procedures; developing experimental studies in animals and clinical trials to determine optimal formulations and dosages of contraceptive agents and hormonal replacement therapies; conducting epidemiological, statistical and clinical studies for post marketing surveillance of reproductive products and collecting and analyzing data from national health surveys, metabolic studies, clinical trials and epidemiological assessments of the health and fertility effects of reproductive drugs.