FROM CELLS TO SELVES

Reproductive Health for the

21st Century

National Institute of Child Health and Human Development
Reproductive Health for the 21st Century

FROM CELLS TO SELVES

i

Contents

The NICHD Mission .................................................................................... 1

The Strategic Planning Process ................................................................... 2

Introduction ............................................................................................... 3

Overall Goals and Objectives ........................................................................................ 3

Scientific Goals of the Strategic Plan ......................................................... 6

Pursue Research Leading to Improved Outcomes in ART .................................................. 6

Use Genetic Advances To Identify Factors Leading to Infertility ......................................... 7

Use Genetic Advances To Identify Novel Contraceptive Leads .......................................... 8

Increase Efforts To Develop Acceptable Male Contraceptives ............................................ 9

Identify New Treatments for Common Reproductive Problems ......................................... 10

Conduct Research on Male Reproductive Behaviors ....................................................... 11

Identify New Strategies for Improving Contraceptive Use ............................................. 13

Study the Behavioral Factors Relating to Infertility, the Use of

Infertility Services, the Ethics of Infertility Treatment, and the

Status of Children Born as a Result of ART ....................................................................14

Increase Knowledge About Healthy Sexuality ................................................................15

Research Technologies and Resources ...................................................... 17

Training and Education ............................................................................ 19

Appendix—Roster of Advisors ................................................................. 21
Reproductive Health for the 21st Century

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1

The National Institute of Child Health and Human

Development (NICHD) seeks to ensure that every individual

is born healthy, is born wanted, and has the opportunity to

fulfill his or her potential for a productive life unhampered

by disease or disability. The Institute further strives to help

parents have the children they want, at the times they want

them, and to ensure that every mother experiences a

pregnancy free of adverse complications. Key to the

success of this mission is answering the fundamental

questions of how a single fertilized cell eventually develops

into a fully functional adult human being and how a

multitude of genetic and environmental factors influence

that process for good or ill. 

Programs at the NICHD are based on the concepts that

adult health and well-being are determined in large part

by episodes early in life, sometimes before birth; that

human development is continuous throughout life; and that

optimal outcomes of development are important not only to

the individual but to society. NICHD research is also

directed toward restoring or maximizing individual

potential and functional capacity when disease, injury, or a

chronic disorder intervenes in the developmental process.

Thus, the NICHD mission truly spans the life cycle, and

much of the health and well-being of our population

depends on the success of the Institute’s research.

The NICHD Mission
During 1998 and 1999, the NICHD staff engaged the

scientific community in jointly developing a strategic plan

to facilitate achieving its mission. The initial framework

document for this plan, From Cells to Selves, highlighted

four areas for immediate strategic development and

described a series of scientific goals under each area.

These four areas were as follows:

• Genetics and Fetal Antecedents of Disease Susceptibility

includes the interaction of the genotype with

socioeconomic, environmental, and psychological

factors in the fetal and postnatal environment that

contribute to health or the pathophysiology of

diseases.

• Reproductive Health for the 21st Century comprises

the biological and behavioral factors that allow

couples to have healthy children when they want them

and the reproduction-related conditions that may

affect women during and after their reproductive

years.

• Developmental Biology: Understanding Normal and

Abnormal Development consists of the basic biological

science necessary to understand early development 

in utero and through the time when many organ

systems form. 

• Biobehavioral Development includes research to better

understand the developmental processes involved in

forming cognitive, learning, emotional, social, and

physical behaviors, and the biological and

environmental factors that make infants, children, and

adolescents more susceptible to behavioral disorders

or to adopting risk-taking and violent behaviors. 

This document refines the goals and objectives outlined

under the area titled “Reproductive Health for the 21st

Century.” 

To help establish the more detailed research agenda that

follows, the NICHD convened a working group

comprising distinguished scientists (see Appendix) from

around the country and asked them to collaborate with

Institute staff to identify and prioritize research goals and

to suggest appropriate strategies to meet those goals.

The working group drew upon ongoing planning efforts,

previous emphasis areas, recent forums, workshops,

conferences, and research findings to develop a draft of

the strategic plan that would guide the Institute’s research

agenda in reproductive health for the next 5 years. 

The draft plan was posted on the NICHD Web site to

allow members of advocacy groups, nonprofit

organizations, the scientific community, and the general

public to comment. In addition, the Institute shared the

plan with members of the National Advisory Child

Health and Human Development Council and with the

Friends of the NICHD, a coalition of more than 100

professional and patient organizations committed to the

Institute’s scientific mission. After consolidating and

reviewing all comments, the NICHD revised and

finalized the plan. This document is intended as a

targeted, but flexible, blueprint that can be modified as

new scientific findings, research opportunities, or

resources become available.

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The Strategic Planning Process
The ability to control one’s own

reproduction encompasses the desire not

only to have children but also to have them

at a time and in a manner that best ensures

their future health, both physical and

mental. Reproductive health significantly

influences the overall health of individuals

and society and has been the subject of

increased attention from a health and

economic viewpoint. The economic burden

imposed on infertile couples attempting to

achieve pregnancy is difficult to estimate

accurately because the cost of treatment is

not always reported as infertility related.

The projected direct cost of assisted

reproductive technologies (ART) together with the cost of

multiple-gestation pregnancies is estimated to be $1.1

billion for the year 2000. The direct cost of unintended

adolescent pregnancies alone is more than $1.5 billion.

Thus, the overall costs of infertility treatment and those of

all unintended pregnancies would substantially exceed

$3 billion annually. These direct costs are in addition to

the considerable indirect costs associated with the

immediate and long-term psychological and other

consequences that accompany both conditions. In

addition, the direct and indirect costs associated with

uncontrolled population growth worldwide are difficult to

comprehend, let alone quantify. Consequently, it is

critical to address these problems from the broadest

possible perspective. 

During the past decade, major advances have been

made in both the biomedical and behavioral sciences

that can be applied to the important issues of infertility

treatment, to the development of improved methods of

family planning, and to the identification of behavioral

factors that affect both fertility and infertility. The

Institute’s strategic plan builds on this solid research

base, much of which was developed with

funding from the NICHD. While leaving

intact the NICHD’s existing areas of

research emphasis, the plan also builds on

the goals listed below, allowing the Institute

to advance the technologies that are

indispensable to achieving reproductive

health without neglecting other research

areas that are within its broad mandate.

Finally, this plan clearly emphasizes the

need for the biomedical and behavioral

sciences to collaborate closely to

successfully accomplish these goals.

Overall Goals and Objectives

To help establish the research agenda for reproductive

health, the NICHD asked the working group, in

collaboration with Institute staff, to identify strategies that

will best achieve the following goals: 

• Pursue research leading to improved outcomes in ART

• Use genetic advances to identify factors leading to

infertility

• Use genetic advances to identify novel contraceptive

leads 

• Increase efforts to develop acceptable male

contraceptives

• Identify new treatments for common reproductive

problems

• Conduct research on male reproductive behaviors

• Identify new strategies for improving contraceptive use

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Introduction
• Study the behavioral factors leading to infertility, the

use of infertility services, the ethics of infertility

treatment, as well as outcomes of children born as the

result of ART

• Increase knowledge about healthy sexuality

The working group based its concept of reproductive

health on the World Health Organization (WHO)

definition:

Reproductive health is not merely the absence

of disease or disorders of the reproductive

process, but rather it is a condition in which

the reproductive process is accomplished in a

state of complete physical, mental, and social

well-being. This implies that people have the

ability to reproduce, that women can go

through pregnancy and childbirth safely, and

that reproduction is carried to a successful

outcome, i.e., infants survive and grow up

healthy. It implies further that people are

able to regulate their fertility without risks to

their health and they are safe in having sex.

This positive definition has several advantages. First, it

emphasizes that biomedical and behavioral research

relating to reproductive health should proceed within an

interdisciplinary context that can accommodate

economic, political, sociocultural, and psychological

factors, while considering other somatic factors—such as

systemic disease or the biological changes associated

with aging—that affect sexual and reproductive function.

The definition also reinforces a key aspect of the

Institute’s core mission, which is to foster collaborative

approaches to problems of reproductive health within the

context of human development.

In addition, the working group felt that the WHO

definition implies that progress in improving the

reproductive health of the world’s population depends on

the attainment of three broad objectives: 

• Reducing the incidence of unwanted pregnancy

• Progressing towards desired levels of fertility 

• Reducing morbidity from diseases and disorders of the

reproductive system

These objectives, without displacing existing priorities of

the NICHD, provide an important structure within which

the Institute’s more focused research goals and agenda

items can be analyzed and ordered:

• The objective of reducing the incidence of

unwanted pregnancy unites the NICHD goals of

using genetic advances to identify novel contraceptive

leads, increasing efforts to develop acceptable male

contraceptives, conducting research on male

reproductive behaviors, identifying new strategies for

improving contraceptive use, and increasing

knowledge of healthy sexuality. 

• The objective of progressing toward desired

levels of fertility unites the goals of improving

outcomes in ART, using genetic advances to identify

factors leading to infertility, identifying new treatments

for common reproductive problems, addressing

behavioral and ethical issues in infertility and infertility

treatment, and increasing knowledge of healthy

sexuality. 

• The objective of reducing morbidity from

diseases and disorders of the reproductive

system unites the goals of improving outcomes in

ART, using genetic advances to identify factors leading

to infertility, identifying new treatments for common

reproductive problems, identifying new strategies for

improving contraceptive use, studying the behavioral

and ethical issues in infertility and infertility treatment,

and increasing knowledge of healthy sexuality. 

This classification demonstrates that the Institute’s nine

scientific goals in reproductive health represent a

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Reproductive Health for the 21st Century

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continuum rather than discrete areas of research,

justifying collaboration not only within the NICHD but

also with other NIH Institutes, Centers, and Offices and

with other Federal agencies. The goals also encourage

collaboration among specialists in biomedical sciences,

behavioral sciences, and social sciences. Sharing

expertise, information, and methodological approaches

is crucial for understanding issues such as how economic

factors affect accessibility to reproductive health services

and how cultural attitudes help to determine whether

specific contraceptive technologies are perceived as

acceptable by various social groups.

The inclusion of healthy sexuality as a scientific goal is

strongly motivated by this emphasis on integrative

research: it reflects a desire to develop a framework that

unifies what could easily be two separate research

agendas involving both the biology and psychology of

individuals, as well as research concerning sociocultural

issues. In addition, because healthy sexuality is

predicated on effective contraception and fertility

management, as well as on the prevention or cure of

reproductive disorders and diseases, its inclusion links all

of the scientific goals identified in this section.

Finally, in view of the Institute’s desire to develop

combined approaches to the nine reproductive science

goals, the working group recommended combining

research focused on male reproductive physiology and

behavior into a single topic. The issue of contraceptive

acceptability is one good reason why these are being

combined because contraceptive acceptability is

predicated not only on physiological criteria (i.e., the

physical side effects of hormonal contraceptives) but also

on individual perceptions, values, and beliefs, which

evolve within specific sociocultural situations.
Pursue Research Leading to

Improved Outcomes in ART

ART encompasses any method beyond natural

intercourse intended to help produce a child. These

methods range from the simple and well-tested to the

complex and controversial. The number of ART practices

has grown faster than the science needed to make

evidence-based decisions in patient care. This has lead

to the empirical choice of treatments at significant cost,

often with loss of time, and in some cases with morbidity. 

Although overall age-specific infertility rates have

remained stable as measured by surveys such as the

National Survey of Family Growth (NSFG), the number

of visits for infertility-related services has skyrocketed.

This increased demand is due primarily to the aging of

the general population and to the delay of childbearing

for economic or professional reasons by a growing

number of women.

Before developing strategic steps to improve ART

outcomes, several key scientific considerations must be

addressed. These include understanding the sequelae of

treatment and developing a definition of “success” for

clinical interventions. This is a highly controversial issue

among clinicians using ART because pregnancy rates

are higher than delivery rates. Therefore, although

many research topics will yield important information

about improved ART outcomes, the main issues are how

to improve pregnancy and delivery rates while reducing

the multiple pregnancies associated with the technology.

A global database using consistent diagnostic and

followup criteria, coupled with the inclusion of a DNA

bank, could yield helpful information. Yet, to fully

understand the nuances of ART outcomes and to answer

the many questions about ART raised by science and

society, it is also critical to support rigorous

epidemiological and basic science research projects. 

Research Areas

• Differentiate between successful (e.g., full-term

deliveries), less favorable (e.g., multiple gestations,

preterm births), and adverse ART outcomes, using

large-scale statistical research, standardized criteria,

and unified assessments. Develop standardized

definitions of “success” and “adverse outcomes.”

Adverse outcomes, in particular, lack standard

definition and tend to be underreported because they

may become apparent only over time.

• Increase scientists’ understanding of the development

of primordial germ cells to mature ooctyes and sperm

through differentiation, meiosis, and maturation in an

effort to evaluate the “quality” of eggs and sperm. 

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Scientific Goals of the Strategic Plan
• Enhance detection of abnormalities in preimplantation

embryos; advance the technology of preimplantation

genetic diagnosis. 

• Understand what constitutes a receptive uterine

environment and how receptivity can be enhanced.

Understand how a healthy blastocyst-maternal tissue

interaction during implantation leads to a healthy

pregnancy and to the well-being of children born as a

result of ART.

• Elucidate the multifactorial causes that lead to

subfertility or infertility in couples and how these

factors, both male and female, interact. Develop

effective methods with minimal side effects to treat

these causes. 

• Understand the nature of the abnormalities either

parent brings into the treatment setting, and identify

those that may constitute risks to the offspring.

Understand age-related fertility factors. These issues

require basic science research to help differentiate

normal from abnormal gametes and to make

epidemiological risk-factor assessments.

• Understand the effects of gynecologic disorders, such

as tubal disease or polycystic ovarian syndrome

(PCOS), on fertility rates and the prevention of

infertility. Understand how these disorders may affect

the choice of infertility treatments.

• Understand the long-term effects of ART interventions

on parental and child health. For example, in women,

this includes the possible connection between ovulation

induction and ovarian cancer; in men, the

transmission of impaired fertility.

• Improve the culturing of immature sperm and ova.

Conduct basic research into cryopreservation and

subsequent maturation of oocytes. 

• Utilize knowledge gained from basic stem cell research

for understanding reproductive processes and for

novel therapeutics.

Use Genetic Advances To

Identify Factors Leading to

Infertility

Little is known about the pathophysiology of infertility,

and many cases remain “unexplained.” However, as the

power of human genetic analysis has increased, the

evaluation of infertile couples has begun to uncover

mutations involving essential factors or processes in

reproductive health. For example, when a mutation

occurs in a critical hormone receptor, the individual may

become infertile because the effect of related hormones

is decreased, even though adequate amounts of the

chemical substances are produced. Likewise, a mutation

in the machinery of the sperm tail movement prevents

these sperm from normally fertilizing eggs and leaves a

man infertile, even though he may produce adequate

numbers of sperm. 

It is possible that many instances of infertility may be

attributable to genetic mutations because reproductive

functions are probably controlled by a very large

number of genes. Thus it is possible that the genetics of

infertility may turn out to be at least as complex as the

genetics of psychiatric illness. As yet, scientists lack a

clear understanding of the overall contribution of genetic

and nongenetic factors to much of female infertility and

almost all of male infertility. Moreover, scientists know

very little about the pathophysiology of germ cell defects. 

The creation of new models is an essential first step in

unlocking the genetics of infertility. This was made

apparent by recent studies identifying numerous genes in

mice and humans that are important during male and

female meiosis, the formation of eggs and sperm, the

process of fertilization, preimplantation development,

implantation, and the complex processes involved in the

origins and differentiation of germ cells. When

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these genes are defective or absent, a variety of

pathophysiological effects will occur, any of which could

lead to infertility. Recent studies in mice have also

shown how gene expression patterns in oocytes, sperm,

and preimplantation embryos may vary under different

experimental conditions, including variations in culture

conditions that clearly influence the patterns of gene

expression. Therefore, researchers can use the full

power of mouse genetics to understand which genes are

normally expressed at each stage of egg and embryo

development, as well as during implantation and germ

cell formation. This in turn will help determine which

genes are abnormally expressed or silent under

conditions of genetic alterations or environmental stress.

Thousands of new mutant mouse strains will soon be

produced through chemical mutagenesis, providing a

vast number of reproductively impaired mouse strains to

aid these studies. 

Research Areas

• Expand basic research on germ cell genetics as a

foundation for understanding impaired reproduction

as well as contraceptive leads. 

• Devise a conceptual framework for the relationship

between epidemiology and basic genetics. 

• Combine genetic/epidemiological approaches to

infertility in human populations, including investigation

into the incidence of familial patterns of subfertility

and infertility and possible modes of inheritance.

• Differentiate the genetic mutations that actually cause

infertility from mutations that do not.

• Identify candidate genes in the general population,

using both classical human genetics and pedigree

analysis with new technologies of genomics and

proteomics.

Use Genetic Advances To

Identify Novel Contraceptive

Leads

Many steps are involved in normal human reproduction,

including production and maturation of gametes; cell

proliferation and programmed cell death; synthesis,

secretion, and action of hormones; fertilization;

preimplantation embryonic development; implantation;

and sex determination. Genetic research involving

reproductive processes, such as meiosis, could reveal

molecular targets that could be the focus of novel

contraceptive leads for both sexes. Potential targets

include coding sequences for proteins or receptors or

regulatory sites that control gene expression.

To identify the most promising molecular targets for

contraceptive intervention requires understanding the

genetic regulation of reproductive processes, a subject

that scientists are just beginning to explore. The primary

goal of genetically based contraceptive research should

be to develop interventions that do not cause widespread

somatic effects. The steps in the reproductive process

that appear most likely to lead to effective and

acceptable approaches are gamete production and

maturation and the fertilization processes.

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The past few decades have seen a dramatic increase in

understanding the genetic control of male reproduction.

In particular, the identification of genes involved in

various aspects of testicular steroidogenesis,

spermatogenesis, and sperm maturation has provided

novel targets for fertility regulation. Coupled with the

increased interest from the pharmaceutical industry in

developing tissue-specific delivery approaches for drugs

and genes, the time appears ripe to capitalize on this

new knowledge about male reproduction to develop

novel contraceptives. 

Research Areas

• Discover associations of gene expression using

discovery strategies and bioinformatics, such as

expression profiling by means of microarrays and

libraries, genomewide mutagenesis, and quantitative

trait loci (QTL) analysis.

• Explore gene functioning at the cellular level using

conditional targeted mutagenesis, RNA targets, and

QTL analysis.

• Study the effects of these molecules at the level of the

organism by using knockouts and transgenesis.

• Develop targeted interventions with minimal side

effects.

Increase Efforts To Develop

Acceptable Male Contraceptives

To develop acceptable male contraceptives from a

biological perspective, scientists must identify processes

that regulate male germ cells without negatively affecting

extragonadal systems. Basic and applied research

during the past decade has uncovered a number of steps

in the gametogenic process in the testes, as well as steps

in epididymal sperm maturation, that may be amenable

to therapeutic intervention. Studies have also shown that

suppressing the hypothalamic-pituitary axis with a

variety of hormonal agents yields severe

oligozoospermia, then azoospermia. Both of these

conditions result in effective contraception. Much of this

clinical research, however, was conducted on a small

number of male volunteers, making it very difficult to

select the more effective and acceptable regimens. 

From a behavioral and sociocultural perspective, males

must also be willing to use these novel contraceptives.

Current data suggest that they may be willing to do just

that: approximately 30 percent of all contraception in

the United States is male based, despite the fact that

abstinence, withdrawal, condoms, and vasectomy are

now the only contraceptive alternatives widely available

to men. Further evidence is supplied by several recent

studies indicating that men will utilize effective, reversible

male contraceptive methods when they become

available; one recent poll has found that up to 70

percent of men are willing to use a contraceptive. 

The lack of progress in developing affordable, safe,

effective, and reversible male contraceptives is due not to

the biological complexity involved in suppressing

spermatogenesis, but rather to social and

economic/commercial constraints. During the past

decade, reasonably safe and effective methods for

reversibly suppressing spermatogenesis have been

developed. Most are hormonally based, but some

immunocontraceptives are now in clinical trials.

However, making these new contraceptives widely

available on the market will require collaborative efforts

that bring together the full spectrum of biological,

epidemiological, and biobehavioral research and their

political interfaces with the public. In the end, all of

these factors must be addressed to help resolve

sociocultural impediments to using these techniques as

well as industry fears of litigation should they choose to

market these novel products. 

Because this topic represents intersecting priorities of all

three branches of the NICHD Center for Population

Research (CPR), it has particular merit, providing an

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excellent opportunity for the CPR branches to collaborate

in developing the initiatives. 

Research Areas

• Identify specific hormonal agents and target their

delivery; support research to design formulations and

methods of delivery that are convenient and

acceptable to men. 

• Design new approaches based on the molecular

biology of the epididymis and testis, including signal

transduction pathways in seminiferous tubules,

somatic-germ cell interactions, and factors that

regulate germ cell differentiation and/or apoptosis.

Increase knowledge about the factors that control

spermatogenesis to facilitate the design of more

specific compounds for male contraception. Identify

new targets that can be explored in animal models

and translated to clinical research and clinical trials. 

• Study behavioral issues surrounding use of new male

contraceptives. This includes the acceptability of such

technologies to men and women and the possible

behavioral issues relating to each of the new

techniques.

• Support epidemiological assessments and analysis of

cost-effectiveness for the various methods of male

contraception. 

• Conduct postmarketing surveillance of the benefits and

potential adverse effects of any new agents introduced

to the market.

• Analyze the long-term health effects, e.g., beneficial or

adverse effects on the prostate and the effects of

androgens on bone mass of these new agents,

particularly synthetic hormones and receptor

modulators. Collaborate with other NIH Institutes,

where appropriate.

Identify New Treatments for

Common Reproductive Problems

A number of conditions have an impact on fertility and

quality of life for women as they progress through the

reproductive years and the postmenopausal period.

These conditions, which can span the reproductive life of

women and include postmenopausal women on

hormone therapy, can result in considerable morbidity,

lowered fertility, and substantial economic burden.

Treatments, however, are frequently empirical and not

based on solid scientific evidence.

Scientists do not understand the etiologies of some of the

most common reproductive problems, including

varicocele in men and PCOS, uterine fibroids,

endometriosis, and abnormal uterine bleeding in

women. Without this knowledge, researchers and

clinicians cannot begin to prevent these problems. In

addition, little is known about the most effective

treatments. For instance, many gynecological conditions

are treated with hormonal manipulation, which may

have unintended consequences. Additional research

must be conducted to identify the etiology and proper

treatment for these conditions.

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New scientific advances promise to speed research in

this area. Knowledge of the roles of sex steroids in

reproductive tissues and nonreproductive tissues (bone,

brain, and cardiovascular) has led to the development of

hormone replacement therapies for postmenopausal

women and aging men. Researchers have also

developed novel selective hormone receptor modulators

known as SERMs (estrogen), SPRMs (progesterone), and

SARMs (androgen). Originally designed to help target

treatment of breast cancer, these agents hold promise for

treating reproductive problems and many other

hormone-regulated conditions in men and women. It is

also clear that specific co-regulators interact with

hormone receptors, resulting in marked tissue-specific

effects for many compounds. This understanding can

lead to new drug development. Conversely, some

conditions are not susceptible to hormonal manipulation,

making the development of nonhormonal therapeutic

strategies also vital.

Research Areas

• Study gynecological issues that are important to

women in their later reproductive years.

• Understand the effects of new specific receptor

modulators (SPRMs, SERMs) on reproductive tissues

and their utility for treating dysfunctional uterine

bleeding, uterine fibroids, endometriosis, and so forth.

• Study the impact (negative or positive) of existing

hormonal treatments and new receptor modulators on

tissues other than the one targeted for therapy. 

• Study the basic biology of the endometrium, including

the factors involved in initiating pathological bleeding.

• Understand the initial phases of these disorders to

discover their etiologies and to develop strategies for

prevention or early intervention.

• Study the secondary effects of these disorders on other

organ systems.

• Better understand the effects of contraception,

hormone replacement therapy, and infertility treatment

on these disorders.

Conduct Research on Male

Reproductive Behaviors

For years, males have been the forgotten partners in

reproductive health. Research into male reproductive

behaviors has largely been neglected because

reproductive issues such as infertility have been

perceived as female related. Similarly, reproductive

health services have been defined around women’s

health needs; moreover, behavioral studies of fertility,

infertility, and contraceptive use have focused largely on

women. The 1994 Cairo Population Conference

identified the development of contraceptives for men as

a component of its women’s health agenda. The

longstanding belief that men would not accept the

responsibility for contraception has been one of the

many barriers to gaining support for worldwide efforts

in developing male contraceptives.

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Interestingly, however, it is estimated that up to one-third

of all contraception in the United States is, in fact,

accomplished with male methods. Recent polls also

indicate that a sizeable majority of men may be willing

to use a contraceptive. However, to identify and develop

the most acceptable methods will take improved

research. For example, to date, male participation in

surveys has been limited, and as a result, there is a

conspicuous lack of data obtained directly from males.

In addition, researchers tend to use paradigms drawn

from studies of female reproductive disorders to discuss

male issues.

Therefore, when studying and developing male

contraceptive techniques, it is important to (1) engage

men as individuals to address their reproductive health,

(2) involve men in larger issues of reproduction and

sexuality that involve women, couples, and society, and

(3) link these issues to the enhancement of children’s life

prospects. In terms of the latter, understanding how men

choose to become fathers and the circumstances in

which they do so is critical to improving the well-being

of families and children. In the end, opportunities to

improve knowledge about men’s access to, attitudes

towards, and use of contraceptive methods will pave the

way for developing new male methods that respond to

men’s needs.

Research Areas

• Study men and couples with regard to perspectives on

gender roles, sexual access and function, fertility

management, and parenting responsibilities to

advance the understanding of fathers and fathering. 

• Understand male influences on the timing of

pregnancy, not only in regard to first births but also in

regard to subsequent pregnancies. Conduct

behavioral research on male contraceptive practice

and on the acceptability of novel approaches to male 

contraception, to complement biomedical approaches

to the development of new male methods.

• Study (1) factors influencing male relationships with

the children of first, second, and later families, 

(2) male investment in childbearing and child rearing,

and (3) the influence of male participation in the

decision to conceive. Study the impact of changing

family and fertility patterns (delayed marriage,

cohabitation, nonmarital childbearing, marital

instability, and remarriage) on male sexual behaviors,

fertility, and fathering. 

• Study male sexuality as a spectrum from basic biology

to health care delivery. Examine men’s attitudes,

values, and beliefs about sexual behavior, sexual

relationships, pregnancy, human immunodeficiency

virus (HIV) and sexually transmitted disease (STD)

prevention, and fathering.

• Study the reproductive behaviors and attitudes of

adolescent males in order to better inform health

providers’ efforts to engage young men in improving

reproductive health. 

• Examine males’ influence on females’ access to and

use of reproductive services. Examine male and

female behaviors related to sex, fertility, and parenting

in the context of dynamic relationships. Study couple

interaction as an important facet of relationship

studies.

• Study the effects of larger cultural factors—economics

and the media, especially advertising—on males’ selfperceptions and perceptions of their own

responsibilities and behaviors. This research may

prove relevant to health disparity studies. Conduct

research on gender ideologies and gender norms,

their antecedents, and their impact on male behaviors

related to fertility, STD risk, union formation, and

parenting.

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• Examine the extent to which pregnancies either are, or

are not, wanted by men: most of the data now

available record women’s reactions.

• Study the incidence of STDs and infertility among

males.

Identify New Strategies for

Improving Contraceptive Use

One of every two pregnancies in U.S. women is

unintended. About one-half of these unintended

pregnancies result from contraceptive nonuse, and the

other half from the ineffective use of contraception or

contraceptive failure. Rates of unintended pregnancy

are highest among women who are young, poor, of

African American or Hispanic origin, or a combination

of these factors. The NICHD has supported substantial

research on individual, family, and societal factors that

are associated with higher risks of unintended

pregnancy. This body of research has contributed

greatly to our basic understanding of these issues but

relatively little to the goal of improving the use of

contraception. Changes in the delivery of health

services and the increasing diversity of our population

have prompted the need to reexamine individual,

institutional, and cultural barriers to accessing and

effectively using contraceptive methods. Recent national

surveys conducted both in the United States and in

developing countries have demonstrated behavioral

changes, including increased acceptance of

contraceptive use, based on the availability of newly

introduced contraceptive technologies.

Research Areas

• Examine the effects on contraceptive experience of

individual risk-taking, partner relationships, STD risk,

and male involvement in pregnancy prevention, across

the reproductive lifespan.

• Research the delivery of family planning services,

including observational studies, clinical trials for new

intervention approaches, and operations research for

integrating and ensuring the sustainability of “proven”

approaches in clinical settings. 

• Study the microbehaviors of contraceptive use and

misuse by men and women, contraceptive

continuation, and the factors that influence these. 

• Research the sustained use of contraceptives and the

reasons behind the discontinuation, inconsistent use,

or switching of a specific technique, especially the role

of side effects and health concerns in such behaviors.

• Study patterns of contraceptive use by individuals in

postabortion and postpartum contexts, as well as

patterns of contraceptive use by individuals after they

have started using a particular method of birth

control.

• Better understand the impact of access to services and

quality of services on effective contraceptive use, from

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the perspective of the potential client. This includes the

organization and content of services, the continuity of

services and followup, and the structure of the delivery

systems in which contraception is provided. 

• Examine methods to integrate contraceptive services

into STD care, male-oriented services, and youthoriented services.

Study the Behavioral Factors

Relating to Infertility, the Use

of Infertility Services, the Ethics

of Infertility Treatment, and the

Status of Children Born as a

Result of ART

Infertility exerts a substantial emotional and financial toll

on affected couples because available techniques have

high failure rates. At the same time, many couples are

denied access to ART services because they lack

insurance coverage or because these treatments are not

provided by public clinics. Ethical considerations

governing who should be given infertility treatment may

also limit access for some individuals, despite the paucity

of research on such ethical issues. In addition, although

little attention has been given to the etiology and

prevention of infertility, two key behavioral factors are

known to contribute to its cause—exposure to STDs and

the trend toward delayed childbearing. 

With delayed childbearing being the norm for many

groups of American women, infertility and infertility

treatment have become critical issues in reproductive

health. In 1995, 1 in 10 U.S. women of reproductive

age had a fecundity impairment, and an additional 3

percent were sterile for reasons other than contraceptive

sterilization. About 15 percent of women had received

some kind of infertility service, with the proportions

sharply higher among high-income women than lowincome women.

Knowledge is needed about the prevalence of infertility

and its antecedent risk factors, decisions made by

infertile individuals and couples concerning the use of

infertility services, the impact of economic and other

barriers to services, and the effects of ART on the health

and development of children born as a result of ART.

Research Areas

• Conduct behavioral, population-based, and clinical

research on ART coupled with biological measures of

reproductive function and child outcomes.

• Study the decisionmaking processes of patients in

seeking and using infertility services, and of providers

in recommending services to patients.

• Examine whether preserving fertility potential might

provide a positive motivational force leading to STD

prevention.

• Examine the effects of oocyte cryopreservation on

delayed childbearing and whether the technology can

influence processes of decisionmaking as to timing of

childbirth.

• Study the obstacles to access to infertility services. This

would include unequal access due to the financial

burden of treatment, as well as sociocultural barriers

to access.

• Study the ethical issues involved in the delivery of

infertility services, including the adequacy of informed

consents and availability of infertility services to samesex couples, unmarried women, or HIV-positive

individuals.

• Discover the disparities in the use of various treatment

modalities, outcomes, and levels of satisfaction among

different sociocultural groups.

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• Study the relationship between insurance coverage

and choices of treatment.

• Study the effect of levels of motivation on the choice of

treatment modalities and long-term satisfaction with

outcomes. 

• Examine the effects of stress on the success of infertility

treatment and treatment outcomes, and identify

appropriate treatments for different couples.

• Study the psychological outcomes of children born as

a result of infertility treatment.

Increase Knowledge About

Healthy Sexuality

Sexuality is an integral part of human functioning. The

healthy expression of sexuality is central to individual

well-being, but under certain circumstances, sexual

behavior also carries potential risks, including

unintended pregnancy, STDs (including HIV), and

emotional or physical harm resulting from unwanted or

coerced sex. 

Despite its significance, healthy sexuality has not been

well studied partly because of the subject’s highly

politicized nature and also because healthy development

is not suited to the problem-oriented model of most

biomedical research. Healthy sexuality, which spans the

life course, must be studied within multiple contexts and

from different perspectives. Important topics include the

emergence of sexuality; sexuality in marriage; sexuality

and aging; sexuality in special populations, including

institutionalized groups, children in foster homes, and

the imprisoned; the intersection of sexuality with disease

and disability; and the aftermath of a nonvoluntary

sexual experience.

Current NICHD-supported work in sexual behavior

consists of a substantial body of research on adolescents

(historically, mainly females) and a few studies of adults

(males and females). Most of these studies examine

individual, familial, social, and community factors that

influence sexual behaviors. There are only a few

projects on the neurology and endocrinology of sexual

behavior in animal models. Likewise, there has been

little research into issues of sexual function and

dysfunction, in either sex, beyond erectile dysfunction in

males. 

Research Areas

• Conduct studies to extend knowledge of human sexual

development and the precursors in childhood of

healthy sexuality across the lifespan; research the role

of the family in promoting healthy sexual

development.

• Research adult sexuality and sexual behavior. Study

the influence of multiple contexts on the expression of

sexuality in collaboration with other NIH components;

for example, questions of sexuality and aging can be

investigated jointly with the National Institute on Aging

(NIA).

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• Study the relationships between illness or disabling

conditions and sexual practice, including the effect of

reproductive cancers on sexuality and the effect of

infection with an STD (including HIV) on sexual

function and sexual and contraceptive behavior.

• Study societies’ management of sexual behavior.

Examine approaches that promote positive sexual

functioning and prevent negative outcomes of sexual

activity in adults; examine effects of individual, social,

relational, and cultural factors.

• Examine the effects of unintended pregnancy and

unintended sex on expressions of sexuality.

• Examine acceptability issues relating to contraception

and ARTs and how various methods or treatments

influence sexuality.

• Comprehend the basic biology and physiology of

normal and abnormal sexual function in males and

females.

• Expand research concerning the prevention, diagnosis,

and treatment of sexual dysfunction in males and

females.

Multidisciplinary Approaches to the Scientific

Goals

Understanding the complexity of factors affecting

reproductive health and sexual function requires

integrating sociocultural sciences with traditionally

biomedical research disciplines. Integrative approaches

are especially crucial for addressing issues such as

equality in access to health services and disparities

among different sociocultural groups, formulating

innovative methods of care, and analyzing the impact of

economic issues on individual treatment choices and on

industry decisions concerning product development and

marketing. Collaborative approaches are also critical in

designing interventions to prevent reproductive

morbidities resulting from STD transmission or

contraceptive failure.

The Institute’s research agenda on reproductive health

requires collaboration not only among investigators and

program officials within the NICHD but also between the

Institute and other parts of the NIH. For example,

interactions with the National Institute of Allergy and

Infectious Diseases (NIAID) will benefit research on

HIV/AIDS, STDs, and gynecological disorders resulting

from infection, while researchers affiliated with the NIA

can join NICHD investigators in conducting research on

sexuality and reproductive issues within the context of

the aging American population. The NICHD already

has shared interests and collaborations with the National

Institute of Diabetes and Digestive and Kidney Diseases

(NIDDK) in the area of urinary incontinence and pelvic

floor disorders, the National Institute of Mental Health

(NIMH) in behavioral aspects of risk for STDs (including

HIV), and the National Institute of Environmental Health

Sciences (NIEHS) in environmental effects on

reproductive function and fertility. The NICHD

investigators can also benefit from establishing

collaborative relationships with experts in fields such as

political science, sociology, psychology, economics, and

demographics: these fields are especially important for

investigating the complex behavioral, cultural, and

economic factors that affect reproductive health and

perceptions of sexuality. Collaboration with industry

would also be productive.

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16
Complementing the scientific goals, the research agenda

must include developing the necessary resources to

accomplish these goals. These resources include tools,

databases, services, technologies, and methodologies

that investigators will need to conduct their studies.

• Collaborative groups of investigators and clinicians to

collect very large numbers of subjects and data, which

generally cannot be provided by individual clinics. 

• Informatics in conjunction with molecular biology and

genetics.

• Genetically engineered animals to study the

pathophysiology of infertility and to determine the

validity of such models to human pathophysiology. 

• New animal models to translate mouse data into

knowledge of other important model systems,

especially large domestic species and nonhuman

primates. These essential models must be further

developed to help identify promising targets for further

investigation into the causes of human infertility and

for conducting infertility studies that cannot be done

on humans. 

• Identification of familial gene deletions resulting in

infertility. 

• Molecular genetic technology and chromosome

technology to perform diagnostic screening tests of

most infertility patients. This will be used to establish

an extensive database and identify known deleterious

genes and abnormalities of chromosomes.

• Cataloging known reproductive phenotypes in

transgenic mice, nonhuman primates, and other

species.

• Generation of expression sequence tags (ESTs) for

reproductive tissues.

• Plans for using data from the human genome project,

which so far has not focused on reproduction,

including ESTs.

• Identification of genetic defects that result in

azoospermia that could be exploited to identify new

contraceptive targets. This would provide a means of

avoiding problems involved in attempting to translate

animal models to human reproductive function.

• Advances in genomics and proteomics of reproductive

tissues as the basis for transgenic animal models and

gene array technology.

• Techniques of gene targeting and of gene array

technology used to define networks of gene expression

in various parts of the female and male reproductive

tracts that can be explored for fertility regulation. 

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Research Technologies and Resources
• Collaborations between public- and foundationsupported research and private industry research to

connect basic science with more applied contraceptive

development work.

• Databases to examine demographic and

biobehavioral information about women’s decisions

regarding the management of reproductive diseases

and disorders.

• New technologies to screen for the benefits and risks

of new compounds without the need for human

subjects to test each candidate (microarray technology

for each tissue).

• Databases to examine demographic and

biobehavioral information about patients’ decisions

regarding the management of reproductive diseases

and disorders.

• Improved methods for measuring and studying male

fertility and family behaviors, dyadic processes and

behaviors, and the inclusion of men in surveys. 

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There is a need for investigators with interest and skills in

a wide spectrum of disciplines and methodological

approaches to conduct research on the broad range of

research agendas relating to reproductive health and

sexuality. An emphasis on training in the following

areas will build a cadre of expert researchers and

enhance progress in meeting our scientific goals:

• Molecular research on reproduction

• Genetic epidemiology

• Steroid biology

• Developmental biology

• Translation of bench research on contraception to

clinical and social marketing research

• Family planning operations research: contraceptive use

and the improvement of contraceptive service delivery

• Outcomes research and cost-effectiveness analyses

• Longitudinal behavioral surveys and research on

couples

• Continued encouragement of multidisciplinary research

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Training and Education
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Warren H. Pearse, M.D., Co-Chair

Jacobs Institute of Women’s Health

Amy O. Tsui, Ph.D., Co-Chair

University of North Carolina at Chapel Hill

Nancy E. Adler, Ph.D. 

University of California, San Francisco

William J. Bremner, M.D., Ph.D.

University of Washington

Aaron Hsueh, Ph.D.

Stanford University Medical Center

Elof D.B. Johansson, M.D., Ph.D.

Population Council

Barbara B. Knowles, Ph.D.

The Jackson Laboratory

Kristin Anderson Moore, Ph.D.

Child Trends, Inc. 

David C. Page, M.D. 

Whitehead Institute for Biomedical Research

Massachusetts Institute of Technology

Robert Resnik, M.D.

University of California, San Diego, School of Medicine

Carolyn Westhoff, M.D.

Columbia University

Appendix—Roster of Advisors

Although this document has benefited from the input of many scientists within and outside the NICHD, and from the

general public, we wish to particularly note the advice of the following members of the strategic plan working group:
For additional copies of this strategic plan, or for more information on contacts or related issues,

please contact the NICHD Clearinghouse at

P.O. Box 3006

Rockville, MD 20847

Phone: (800) 370-2943

Fax: (301) 496-7101

Web: http://www.nichd.nih.gov/publications/

For additional information about other NICHD strategic plans and research, please visit our Web site at

http://www.nichd.nih.gov/