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Reproduction White Paper (PDF - 639KB)

Created on March 15, 2011



32 Submitted Comments on Reproduction
I would ask that the order of the issues be changed. Are they in priority order now? If so, I am concerned. I mentioned to a colleague that I was happy to see that quality of life related to reproduction was a major heading. My colleague responded, yes but that is not science. In my view if we put quality of life in women around reproduction as the first item, and top priority, in the report in the end that will serve the science around all of reproductive health the best. If we commit to the best care and research on what that is as a top priority all of the other efforts will follow. We are the National Institues of Health. Please do what you can in this report to make it clear that you consider quality of life research important science that can improve the quality and relevance of the other science that we do around reproductive health. A clear statement to this affect from the Director would be much appreciated.

Submitted by Lawrence Nelson on March 22, 2011 at 12:24 PM
I read this white paper with interest. As an economist, I know of a significant amount of new research examining the relationship between health and fertility and socioeconomic outcomes. I think the inclusion of this research (and the associated statistical techniques) could enhance the breadth of this proposal. I have identified a number of places where I think the application of economic techniques would strengthen the conclusions of the project. They are: 1. The relationship between health and disease and reproductive health and disease (in particular, understanding the causal channels). (page 1) 2. Understanding the interaction of genetics, environment, behaviors and socioeconomic status. (page 1) 3. Improved understanding of the risk factors for unintended pregnancy and the social and cultural behaviors that facilitate or detract from the correct and consistent use of contraceptive methods. (page 4) There is already some recent work in developing countries looking at information and contraceptive use that might be useful/relevant. 4. The general "quality of life" component could easily incorporate econometric methods to understand underlying relationships/causal channels. 5. This is also true for the "reproductive health as a window to overall health" component, which seeks to link reproduction and social behaviors, etc.

Submitted by Sandra Black on March 28, 2011 at 3:19 PM
Recommend adding a few edits to include pelvic floor disorders and gyn issues in the document. on page 2 in the paragraph: Women with gynecological diseases and reproductive tract disorders may experience quality of life issues, which can be impacted by related co-morbid conditions such as infertility, "urinary and fecal incontinence, pelvic organ prolapse," obesity, metabolic dysfunction, chronic pain and mood disorders. Improving therapies and developing novel approaches to diagnose and manage these interrelated conditions may provide opportunities for quality of life improvements in diverse populations and across the lifespan. Quality of life should be assessed at baseline and throughout all clinical studies. Page 7 under Expansion of Global Reproductive health: ?We believe a global reproductive health study is possible and propose to build a global infrastructure for data collection at the level of the clinic and population. This will require the development of appropriate informatics to collate large data sets and the tools to integrate information from all aspects of reproduction: maternal, fetal, and diseases and morbidities of the resultant child and adult diseases of the ?parents.? The global context will permit, e.g., an understanding of the lifetime burden of obesity (and-delete), diabetes and fecal and/or urinary incontinence and pelvic organ prolapse from pregnancy and delivery on reproductive health. This could also include the impact of the environment and provide unique opportunities such as understanding the wellbeing of mother and child through IVF and even the appropriate utility of IVF in unexplained subfertility, including comparative research between IVF and diagnosis-specific treatment (e.g., studies that could not easily be accomplished domestically.) Page 9 under Reproductive Health as a Window to Overall Health: ?Reproductive health addresses reproductive processes, functions, and systems throughout life and implies responsible reproduction and a responsible, satisfying, and safe sex life. It is also essential to overall wellbeing and involves the freedom to decide if, when, and how often to reproduce (WHO definition). We identified more than 100 medical conditions associated with reproductive dysfunction, including "gynecologic disorders such as vulvodynia, fibroids, fecal and urinary incontinence, pelvic organ prolapse, as well as" obesity, heart disease, diabetes, mood disorders, cancers, STDs, and

Submitted by Jason Woo on April 1, 2011 at 8:34 AM
Although much of the document is not related my expertise, the document as a whole is very comprehensive. I have a minor issue: I wonder if the terms "conceptual," "pre/peri-conceptual" are appropriate in the context of describing human conception. The dictionary describes "conceptual" as term with a broader meaning (as in " developing a conceptual framework for the visioning process workshops"). It is not the same as "conception" used in the context of reproduction (as in, "the gestational age is the time from conception and to the time of birth") So, should it not be ".. conceptional" instead? This is a minor issue, of course. Thank you. Tonse

Submitted by Tonse Raju on April 1, 2011 at 9:27 AM
I am sure this is not the right moment politically, but at some point the NICHD has got to be willing to fund research into how sexual orientation is established. It is a fundamental biological question that only a few brave basic researchers have ventured into on their own dime.

Submitted by Anonymous Guest on April 1, 2011 at 2:46 PM
Seems like a major waste of time to be setting these goals given the lack of funding at the NICHD.

Submitted by Anonymous Guest on April 6, 2011 at 7:57 AM
I echo another comment about "conceptual," and "pre/peri-conceptual." You should be referring to conception(al) and pre-conception(al). As I have taught my students "preconceptual "refers to not having formulated an idea upon which to act, which in reproductive circles, ends up with unintended pregnancies! The correct terms should be preconception and conception, which refer to the reproductive act and surrounding health behaviors and decision-making.

Submitted by Anonymous Guest on April 6, 2011 at 10:14 AM
The paper succinctly touches upon many of the key aspects of human reproduction and development ranging from fecundity, fertility, development, and life course. The paper is responsive to the emerging early origins of disease and health paradigm, including the testicular and ovarian dysgenesis hypotheses and growing recognition that reproductive health may be informative for women's gravid health and later onset disease in both men and women. The authors have conceptually addressed a host of applicable biomarkers and research opportunities at the basic, clinical and population level underscoring the role for team science. Once area that might receive further attention is the development of prediction models relevant at for clinicians and public health practitioners.

Submitted by Germaine Louis on April 20, 2011 at 1:21 PM
Apparently the reproduction topic has very little to do with healthy pregnancy past the point of implantation. I was shocked at how research to improve pregnancy health and treatment of pregnant women was largely ignored. However, given the slant of the members who participated (very few obstetricians) I should not be surprised. Shame on the NIH.

Submitted by Anonymous Guest on April 28, 2011 at 1:03 PM
The white paper rightly acknowledges the global scale of the issues within the field of reproduction. Clearly, the white paper it is intended to address challenges facing individuals and couples in regard to reproduction in developing countries (noting the reference to the MDGs). The workforce section could be strengthened by identifying ways to develop greater understanding of the challenges of contraceptive use/reproductive health in different countries with different social and cultural contexts. Addressing the scientific opportunities in contraception will require researchers who have a deep understanding of the realities of sexual life/health in very different settings. Can we provide opportunities for western researchers to gain those experiences? Can we learn from the researchers in developing countries and provide them opportunities to strengthen the work that will eventually benefit their countries? The section on contraception takes very complex concepts and reduces them to phrases, such as identifying the determinants of contraceptive use and non-use?. That simple phrase encompasses understanding the limitations of the health system, the cultural pressures to reproduce and the interpersonal dynamics in settings where gender roles are highly prescribed. There are many scientific opportunities here.

Submitted by Wendy Baldwin on May 9, 2011 at 5:54 PM
The Society of Gynecologic Surgeons has reviewed the NICHD white papers. As a group of health care professionals and researchers committed to the highest standards for gynecology, female pelvic floor disorders (PFDs), and women?s health, we wish to provide several comments for consideration by NICHD when establishing its future vision. In general, we were disappointed that PFDs, including urinary incontinence, pelvic organ prolapse, and fecal incontinence, were not mentioned in any of the White Papers. These disorders are certainly a part of women?s reproductive and post-reproductive health and we believe, are directly in line with the mission of the NICHD. The societal and personal burdens of PFDs and their associated treatments greatly impact women?s quality of life and functioning. Millions of women are affected by PFDs and at least 1 in 11 women will have a first surgery for urinary incontinence or pelvic organ prolapse before age 80. Each year, > 225,000 inpatient surgeries are performed for pelvic organ prolapse in the U.S. at an estimated cost of over $1 billion. The frequency of surgery is twice that of breast cancer and 3 times that of prostate cancer. Surgery alone is not always effective in the long run; nearly 30 percent of women report continued problems over a five-year follow-up period. Support for research at all levels is critical to address the growing demand for high quality, evidence-based care for an aging population suffering from PFDs. Research investment is urgently needed to address major knowledge deficits in the following areas: ?Basic research to understand the biology, mechanism, and causal, mediating and preventive factors for PFDs ?Investigation into the role of genetic variability and environmental factors on phenotypic outcomes of PFDs, and linkage of phenotypes to the progression of PFDs and risk of treatment failure ?Improvement and modernization of diagnostic, assessment, and outcome measurement tools ?Development of novel therapies and treatment approaches, methods to improve the specificity of PFD treatments, streamlined clinical trials methodology, and clinical effectiveness research NICHD?s commitment to improving and developing approaches to improve quality of life across the lifespan directly applies to PFDs. It is our hope that the NICHD recognizes the growing issue of PFDs and its significant impact on the health, function, and well-being of millions of women when developing its future vision.

Submitted by Soc Gynecol Surgeons on May 10, 2011 at 1:48 PM
We read with great interest the white papers on pregnancy and reproduction and agree with the importance of many of the ideas presented. We are deeply concerned, though, with the almost complete exclusion of the social science perspective and, particularly, economic analysis. The primary oversight is the implicit view that pregnancy and reproduction are largely outcomes that result from biological processes. The role that behavior plays is almost completely ignored. We need to understand both the biology and the behavior if we interested in research focused on promoting that ?every child is wanted and reaches their full potential.? If we only know how the body works, but not how or why individuals make decisions, we will fall short of that goal. For decades, economists have usefully studied fertility. For illustrative purposes, we describe some of our own work on teen and non-marital childbearing. One advocated approach to reducing these pregnancies is to increase access to contraception. Improved access will only be effective if women are committed to avoiding pregnancy and that it serves those who were not already using contraception. This is about behavior, not biology. We investigated how expanded family planning services under Medicaid affected fertility, finding that the policy reduced births to newly-eligible women by almost 9 percent (Kearney and Levine, Review of Economics and Statistics, 2009). We have also explored how background disadvantage affects rates of early childbearing (Kearney and Levine, in An Economic Perspective on the Problems of Disadvantaged Youth, 2009.) We confirm a strong empirical correlation at the individual level, but find that even large changes in the rates of disadvantage among a cohort would not be very effective at reducing aggregate rates of teen childbearing. Levine has used econometric tools to examine the impact of abortion policies on pregnancy and childbearing (Levine, Sex and Consequences, 2004). Kearney has empirically examined the impact of the welfare reform ?family cap? (Kearney, Journal of Human Resources, 2004). The purpose of this comment is to advocate for the value of social science research, and economic analysis in particular, in addressing critical issues in reproductive health. It would be a complete travesty if the insights and analytic methods of social scientists, including economists, are excluded from the NICHD vision.

Submitted by Melissa Kearney on May 18, 2011 at 2:16 PM
While research on prenatal testing and screening has been thought to be the exclusive domain of biomedical researchers, insights from economics and decision sciences - much of it funded by NICHD - have improved our understanding of these tests, how pregnant women make decisions about them and ways to help them improve their decision-making. Economists and decision-theory scientists have made important contributions to our understanding of how to conceptualize these decisions processes and help expectant parents make more informed decisions. Research by Fajnzylber, Hotz and Sanders (2010) [FHS] funded by NICHD (R01HD34293) contributes to this by recognizing that pregnant women may take account of the fact that outcomes for one pregnancy affects future fertility choices. In their model, an amniocentesis carries with it the risk of experiencing a miscarriage but women, by not undergoing an amniocentesis, can limit this risk. At the same time, by not having an amniocentesis, pregnant women increase the risk of bearing a child with Down syndrome. In FHS?s model, pregnant women will take account of the fact that if they experience an amnio-induced miscarriage, they have the option of still having a chromosomally-normal birth at later ages as well as the fact that this option decreases as these women approach menopause. The latter two points distinguish FHS from other genetically-determined or static decision-theoretic models of amniocentesis choice. The former models will always have a rising propensity to choose to undergo an amniocentesis to the extent that pregnant women prefer to avoid a child born with a genetic disorder. But the dynamic model of FHS, the propensity of women to choose an amniocentesis may or may not rise with maternal age. Since they balance the benefits associated with having an amniocentesis (avoiding having a child with a genetic disorder) with the costs associated with them (running the risk of a procedure-induced miscarriage of a healthy fetus). FHS show that their model can explain the following two ?stylized facts? about how amniocenteses vary with pregnant women?s age and birth parity. First, while amniocenteses begin to rise at age 35, they decline after age 40. Second, this decline in amniocenteses at older ages is greater for women who had not yet had a birth than for those with 3+ children. Based on calibrated simulations of their model, FHS show that they can account for both of these stylized facts.

Submitted by V. Joseph Hotz on May 19, 2011 at 5:16 PM
In general this white paper is on target. The only issue that I have wth it is that the increasngly important field of mechanical signaling- signaling due to changes in cell shape and architechure -is totally ignored. In view of the dynamic nature of development this would seem to be a critical new area ot foster in reproductive biology.

Submitted by Anonymous Guest on May 20, 2011 at 3:36 PM
The White Paper emphasized the importance of research from biology, genetics and medicine. In contrast, little consideration was given to the role of economic research. Economists have made several contributions to knowledge about human reproduction. Consider the issues of contraception and unintended pregnancy. Economists have long studied the determinants of fertility. As part of this research, economists have made significant contributions to knowledge of the determinants and consequences of unintended pregnancy. One of the most important contributions economists have made is demonstrating that the prevalence of unintended pregnancy depends on the prices and efficacy of contraceptive methods, and the costs and benefits of having and raising children. Economists have used this insight to make empirical progress toward assessing the consequences of unintended pregnancy and unwanted birth. By using variation in unintended pregnancy due to changes in the costs of contraception, economists have been able to identify more credibly the consequences of unintended pregnancy on infant and child development. This has been a particularly important innovation because information about unintended pregnancy and unwanted births is drawn from surveys of mothers, which for a variety of reasons will measure unintended pregnancy and unwanted births with considerable error. Similarly, economists have used changes in the availability of abortion in the United State and other countries to measure unintended pregnancy and unwanted birth, and linked changes in abortion availability to infant health and child health and wellbeing. Another important insight of economic research is the notion of competing risk of illness and death, and how that influences contraception use with "dual purpose", for example use of condoms to prevent pregnancy and prevent HIV infection. Economists have shown that prevention depends on much more than the cost of the specific preventive tool. In the case of condom use, or contraception in general, the cost of contraception is just one, arguably small, influence. The costs of the consequences of not preventing may be much more important. This concept has been shown to be an important explanation of salient reproductive-related health problems. For example, economic research has shown that condom use in parts of Africa is low because life expectancy and the quality of life is low in these parts of Africa.

Submitted by Robert Kaestner on May 27, 2011 at 1:05 PM
The determinants and consequences of unintended pregnancy are a significant area of research proposed in the NICHD White Paper on Reproduction. Economists have contributed importantly to our understanding of the impact of unintended pregnancy on individual well-being. The 1995 Institute of Medicine (IOM) report on unintended pregnancy concluded that children from unwanted conceptions were at greater risk of being born low birth weight, of dying in the first year of life and of being neglected emotionally and intellectually as children. However, in a series of papers, economists demonstrated that prior evidence of a causal link between unwanted pregnancies and adverse outcomes was tenuous. Much of the evidence in the IOM report failed to adjust effectively for confounding factors such as family background. With greater attention to the appropriate counterfactual, economists demonstrated that many of the purported adverse associations of unintended pregnancy were not present if comparisons were made between siblings. The results have important policy implications. For example, they suggest that simply delaying a first birth beyond adolescence is unlikely to have nearly the benefit implied by correlations emphasized in the IOM report. Economists have also developed novel methods to analyze the impact of induced abortion on the well-being of children and families. Induced abortion is widespread and arguably a more direct measure of unintended pregnancy than postpartum assessments obtained from women who give birth. Using cross-cohort comparisons before and after the legalization of abortion, economists have shown that access to safe, legal abortion has improved the circumstances of cohorts by diminished exposure to poverty and increased schooling. The recent emphasis in applied economic research has been towards greater internal validity and more transparent analysis. Since randomized controlled trials are unethical for many of the questions of interest in the White Paper, economists bring important empirical skills and theoretical perspectives that can contribute to the research agenda envisioned by NICHD.

Submitted by Ted Joyce on May 27, 2011 at 1:33 PM
The White Paper lists topics from a biomedical perspective, but it neglects much of the research and data supported by NICHD in the behavioral sciences. Economists and social statisticians have challenged many causal interpretations of clinical and population data on the determinants and consequences of fertility. Economists have also recognized their limitations to infer cause and effect relationships involving behavior and biology. They have thus resorted to randomized experiments and structural models to assess causal relationships between technological opportunities, socioeconomic behavior, and health and welfare outcomes.
My research found that women's use and choice of contraception appeared to depend on their expected fecundity, or their past reproductive success with their partner. The framework was consistent with contraceptive choice and fertility in the US (1985) and in Malaysia (1987). This implied that many biomedical or demographic calculations of the efficacy of improved birth control methods were probably underestimated, because they neglected the systematic choice of more fecund couples to use more effective methods. Fertility determinants are difficult to access because people have different (unobserved) "demands" for fertility (not to be confused with subjective reports of "wanted" births), as well as different fecundity (supply). Unless inferred from randomized experiments or approached in a suitable causal model, the key risks of reproduction cannot be deduced. Public policies and research priorities may then be premised on misleading non-causal studies. The notion that preferences and biological capabilities both account for reproduction has of course evolved in the subsequent 35 years. NICHD supported my early research.
Improved contraceptive technology, reproductive and child health inputs, and preventive health interventions provide women with improved control of their reproduction and child health and warrant study. Important hypotheses are advanced, but rarely tested empirically, that suggest the increased certainty in reproduction has: (1) freed women of tasks, allowing them to allocate time to activities outside of the home that entail social benefits and increase women's wages, (2) fewer births per woman have increased the survival, health and schooling of women and their children, and (3) fewer children encourage women to accumulate more life cycle wealth that adds to their later consumption opportunities and well

Submitted by Paul Schultz on May 27, 2011 at 8:59 PM
The Endocrine Society commends the inclusion of behavioral aspects of reproductive health in the Reproduction Vision white paper. However, the initiatives could be further expanded and could benefit greatly from the inclusion of research aims involving behavioral aspects of early pregnancy, both planned and unplanned. Contraception issues should include factors encountered by young mothers, such as sexually transmitted infections and the lifetime implications of early pregnancy. Analysis underscoring the behavioral component of the Reproduction Vision, such as factors influencing the decisions of young women, would be a valuable addition to the strategic plan as it would inform efforts to develop programs to empower and educate young women.
We are pleased to see that genetic, epigenetic and environmental interactions are listed as a cross cutting theme. The Society recommends that discussion of the interactions between genes, epigenetics and the environment be woven into each of the themes of the Reproduction Vision, and that further emphasis on the interactions between the environment and genetics in the outcome of pregnancy be included. We also recommend the inclusion of endocrine and non-endocrine autoimmune diseases that influence reproductive capability, as well as diseases/disorders that are influenced by reproductive lifespan - both those that improve and those that may worsen as a result of reproduction.
Additionally, the white paper emphasizes the early stages of reproductive health and folliculogenesis, but does not include sufficient discussion of the late stages of reproductive health, such as the role of apoptosis and senescence in the ovary. Deeper understanding of these processes could inform efforts to prolong the reproductive lifespan in women, particularly those at risk for an early menopause.
Inclusion of diagnostics and treatments for reproductive health, such as the preservation of reproductive capacity, would be important to include as the field will likely develop significantly over the next ten years. Oocyte and ovary preservation are important treatment options that have not been well studied, and measures should be taken to develop similar strategies for the preservation of male fertility in the next decade. These approaches are out of reach for most of the world's developing countries, and in the future, strategies should be developed to determine fertility preservation methods that will be accessible to all populations.

Submitted by Kelly Mayo on June 1, 2011 at 11:33 AM
I appreciate the NICHD's planning process and the ability to provide feedback. In reading the white paper, one gets a renewed realization of how truly broad the mission of this institute is. In a time of limited resources, covering such a portfolio is daunting. The goals are broad and ambitious.

There is an emphasis on human and non-human primate work. Such work is needed, but non-primate animal model work is also necessary. Costs and regulatory burden involved in primate research can restrain research progress. The tools are also limited. Work in rodent and other model systems can make primate work more efficient.

There is an emphasis on overall heath but almost a seeming lack of emphasis on physiology. These seem to counter one another. GWAS, "omics" and the like are providing incredible information to help us understand reproductive processes and these approaches must continue, but pairing these with creative hypothesis-based physiologic studies is required to understand mechanisms. Overall health results when the intact organism integrates all its omics to produce an overall physiologic milieu. The need for original basic/clinical science in all mission areas cannot be overemphasized.

Finally, there is a large emphasis on quality of life. This is an important outcome but I have two levels of concern. The first is that QoL is difficult to evaluate and can be affected by things outside of reproductive health, such as economic conditions. The second is to consider if QoL should be an NIH-wide initiative, perhaps removed from under individual institutes so that there is a more uniform approach to this critical aspect.

Submitted by Sue Moenter on June 2, 2011 at 12:26 PM
An oversight in this otherwise stellar report regards the implications for fundamental biology which have been and are continuing to be discovered by investigations in reproduction, as well as the invaluable contributions of this field for launching the careers of tens of thousands of NIH-sponsored investigators. Studies with gametes, zygotes and embryos pioneered the explosion in cell cycle checkpoints with invaluable implications for cancer diagnostics and therapeutics. Nuclear architecture and chromatin remodeling findings were all pioneered first in these preimplantation tissues, as was the entire field of genomic imprinting and epigenetics. Motility and cytoskeletal dynamics, starting by discoveries in the swimming of sperm, have lead to appreciations of nanomotor involvement in mitosis and meiosis - critical for avoiding premature aging, birth defects as well as cancers. Cell signaling, cytoplasmic inheritance, gene expression and systems biology all also owe their intellectual origins and indeed their future directions to reproductive investigations. Furthermore, many of these systems are routinely tractable for advanced research training programs at Universities as well as independent research institutions. Finally the powerful molecular models for most every human disease are being generated by the protocols developed for mouse embryos and mouse embryonic stem cells. Consequently, it is vital that the NICHD does not ignore its rich tradition and invaluable future contributions in fundamental cell, molecular and developmental biology derived from the creative investigations on gametes, zygotes and embryos.

Submitted by Gerald Schatten on June 8, 2011 at 3:02 PM
The white paper appropriately stresses the importance of research on both the biological and behavioral/social aspects of reproduction. One neglected opportunity in behavioral research is to develop more sophisticated measures of the social and cultural environment. "Ambivalence" about pregnancy and ineffective or nonuse of contraception are functions of the intersection between economic and social circumstances and cultural meanings of contraception and reproduction. Improved characterization of these phenomena will produce new insights for the development of effective interventions at both individual and population levels.
The section of the white paper on quality of life is intriguing but appears to encompass all of social and behavioral science as well as health. While applauding the concept that research and clinical care need to consider the lives and contexts of patients, I would strongly encourage a critical interdisciplinary assessment of the science contributing to the many different questions posed in this section as well as the development of focused studies in which to explore the value of the approach described.
The white paper does not address disparities in reproduction. Although infertility treatment is mostly accessed by advantaged populations, data from the National Survey of Family Growth documents that low-status women suffer disproportionately from infertility. This deserves further study; it also underscores the need for population data and demographic expertise in framing the NICHD agenda in reproduction research.
Demographic studies of reproduction are a signature contribution of the Institute. These studies not only provide the framing just mentioned, but also contribute scientific knowledge of the basic economic, social and behavioral processes that lead to various patterns of contraceptive use, conception, and reproduction. Investigator-initiated, demographic and social science research on reproduction is currently used extensively by federal policy-makers and NICHD is the only source of federal funding for it. Investments by the NICHD played an important role in reducing rates of teen pregnancy; with the prevalence of nonmarital fertility at an all time high and fertility rates falling below replacement in the non-immigrant population, this research remains critically important.

Submitted by Christine Bachrach on June 9, 2011 at 3:24 PM
As an economist working on demographic topics, I read the White paper on reproduction with great interest. Below, I will briefly describe
some work that I have done on understanding how access to abortion and birth control methods affects child outcomes and fertility behavior. I
make progress on these classic questions in demography using Romania's unique history of access to abortion and birth control methods. In 1966, Romania's dictator Nicolae Ceausescu declared abortion and family planning illegal and maintained this strict policy until 1989, the year of the fall in communism in Romania. I argue that the implementation and repeal of the restrictive regime provide a unique exogenous source of variation in the cost of birth control methods that is arguably orthogonal to the demand for children. In a first paper using this unique social experiment (The Impact of a Change in Abortion Regime on Socio-Economic Outcomes of Children: Evidence from Romania, Journal of Political Economy 114(4), 2006), I analyze the channels through which an abortion ban affects educational and labor market outcomes of children affected by the policy. The main result of the paper is that after controlling for the composition of women giving birth using observable background variables, I find that children born after the ban on abortions had worse educational and labor market achievements as adults. In another paper (The Supply of Birth Control Methods, Education and Fertility: Evidence from Romania, Journal of Human Resources 45(4), 2010) I argue that Romania's 23-year period of continued pronatalist policies can be useful to address a long debate in the demography literature about the relative importance of demand-side and supply-side factors in explaining fertility levels and the fertility differential by educational groups. The main result of this analysis is that the supply of birth control methods plays a significant role in determining fertility levels, particularly for less educated women.
The above papers are based on the application of statistical methods ("natural experiments") using large micro datasets, which are commonly used by applied economists in a variety of fields. The inclusion of such research would in my opinion broaden the current proposal.

Submitted by Cristian Pop-Eleches on June 9, 2011 at 4:26 PM
The Society for Women's Health Research appreciates the opportunity to provide comments to NICHD's Vision process. SWHR's recommendations to the Reproduction Workgroup in the context of health and environmental research is the importance of complete analysis looking at both maternal and paternal health and exposures, before, during, and after conception, and the ultimate impact on health. Too often the common focus on environmental health reproductive research is on the mother while pregnant. SWHR strongly encourages the Reproduction Workgroup to broaden the scope of reproductive research, and to seek out and report sex based differences.

As there are clear sex differences already noted in the incidence, diagnoses, treatment and outcomes relating to diabetes, obesity, autoimmune diseases and coronary heart disease, one would expect that these differences can be traced back to early childhood and development. Women's total health, not just reproductive health, is impacted by reproductive hormones (natural, exogenous, and environmental). The effects need to be studied over the total life span-not limited to reproductive years or to effects on fecundity and fertility, exclusively.

As the thought leaders in research on sex differences, it is SWHR's hope that NICHD will be recognize the importance of sex as a variable, and will encourage the analysis and reporting of sex-specific differences.

Submitted by Leslie Stevens on June 9, 2011 at 4:53 PM
Attention to health disparities is one of the guiding principles (p3) in this vision paper. Disability is a recognized category within health disparities http://www.hhs.gov/ocr/civilrights/resources/specialtopics/health_disparities/index.html though it is often overlooked). As health disparities in reproduction are considered, it is essential to include issues for both men and women with disabilities. Aside from the typical issues raised, there are issues that seem to be frequently missed, including [1] The effects of menstruation/cyclical hormonal changes on the cyclical functional capacity of women with disabilities (eg cerebral palsy, multiple sclerosis, traumatic brain injury, etc) has received little attention even at the most fundamental levels of providing information for ways to manage personal monthly hormonal cycles so as to preserve functional capacity. Little is known about the impacts of reproductive system changes on daily function. For example, activities that a woman may be able to perform throughout most of the month, may become much more difficult or even impossible during certain parts of the menstrual cycle. These fluctuations need to be considered in building an adequate personal support system, based on fluctuating functional requirements. Health personal are not trained about these issues. And the area as a whole has, for the most part, received little attention. [2] Maintaining sperm viability in men who use wheelchairs for mobility. (though this area has probably received considerable more attention than the first issue raised above. ) [3] the functional effects of changing reproductive hormone level s in both women and men who are aging with a disability.

Submitted by Alexandra Enders on June 10, 2011 at 1:11 PM
The National Women's Health Network and the Reproductive Health Technologies Project are women's health advocacy organizations that do not take financial contributions from any entity with a financial stake in women's health decision-making. Thank you for the opportunity to comment on NICHD's Reproduction Vision Process.

We are pleased that several of the crosscutting themes which emerged during the workshop address the impact of behavioral and environmental factors on reproductive health. We support the need for fundamental and applied contraceptive research on both newly developed and existing methods. This research is essential to understand the behavioral issues related to contraceptive use and non-use in various settings and populations. A deeper understanding of these issues will inform efforts to reduce the number of unintended pregnancies. We also support the crosscutting theme calling for a better understanding of a variety of developmental processes, including the impact of the environment and altered nutrition/disease on reproductive function. In particular, we would like to encourage NICHD to continue its efforts to conduct research on the safety and effectiveness of oral contraceptive pills for women who are overweight and obese.

We would also like to highlight the importance of the crosscutting themes related to reproductive research more generally. We agree it is essential to reevaluate the design and conduct of clinical trials as they relate to reproductive research. For example, there is not nearly enough information on the impact of prescription medication use on pregnant and lactating women largely because women who become pregnant during a clinical trial are immediately discontinued. Instead, these women should be offered the opportunity to stay in the trial by re-consenting according to the new potential risks; this would facilitate a safer way to gather data on this population. We also agree that mutual benefits could be leveraged through increased community participation and engagement in research. This type of engagement could ensure that the reproductive research conducted is able to answer the questions real women have about their health.

Submitted by Kate Ryan on June 10, 2011 at 2:08 PM
The Population Association of America (PAA) is pleased to comment on the Reproduction white paper.

The conceptualization of research directions outlined in this paper includes many opportunities for behavioral research, including that being done by demographers. Yet, more detail is needed to clarify how the population sciences, in particular, can contribute.

At multiple points, the paper recognizes reproduction as a nexus for the interaction of biological and environmental factors. However, in some sections the "scientific opportunities" seem narrow and biological. For instance, the white paper's introduction to pre/peri-conceptual health and pregnancy (II.I) begins broadly (p.3): "...to understand the effects of pre/peri-conceptual physical, environmental and psychological health in females and males". But the "scientific opportunities" (1 through 5) are focused on the "physical."

An exception is II.2 CONTRACEPTION where the first scientific opportunity is:

1) Improved understanding of the risk factors for unintended pregnancy and the social and cultural behaviors that facilitate or detract from the correct and consistent use of contraceptive methods.

This is an important area of research and is a research focus of many PAA members. The infrastructure (human capital and appropriate data and other resources) is in place to make significant gains in this area.

II.3. DEVELOPMENTAL ANTECEDENTS is similar to II.1 in that it begins broad (including the interaction of biological and environmental factors) but the scientific opportunities are narrow biological foci. An exception is II.3.4:

4. Determined the roles of the environment ...

The final sections have multiple opportunities for behavioral science contributions. For instance:

III.4 Expansion of Global Reproductive Health. This opportunity is very "demographic" stressing "lifetime burden" of disease and comparative research.

III.5. Quality of Life. This opportunity focuses on holistic assessments and population based tools and techniques.

III.6. Reproductive Health as a Window to Overall health. Viewing reproductive health as interrelated to general health and linking to social behaviors (III.6.4) places it in the domain of behavioral research, including that done by demographers.

Submitted by David Lam on June 10, 2011 at 2:09 PM
The National Women's Health Network and the Reproductive Health Technologies Project have been long-time advocates for many of the scientific opportunities identified in the white paper. We are extremely pleased that NICHD has stated that in ten years it will have taken the lead in contraceptive R&D and strongly support the priorities outlined in the contraception section. We agree with the assessment that new and innovative methods have not been forthcoming from the pharmaceutical industry and support NICHD's goal to change the research paradigm in this field.

We support the development of scientifically sound tools to improve understanding of the risk factors for unintended pregnancy, inconsistent contraceptive use, and contraceptive failure. By identifying the determinants of contraceptive use and non-use and determining what interventions can increase use and decrease contraceptive failure, NICHD can better direct present and future R&D. A better understanding of how and why current methods are used and their impact on specific populations can help ensure the most effective use of current methods and can also help guide development of innovative new methods. Women should have more contraceptive options that better meet their changing needs throughout their reproductive lives and directing R&D based on women's preferences is a step towards achieving that goal.

We commend the institute for prioritizing the development of new methods. Specifically, we strongly support the development of new dual purpose contraceptive methods that also offer protection against HIV and other sexually transmitted infections. In addition to contraceptive options for men, we also strongly support the development of innovative non-hormonal contraceptive methods for women, including barrier methods. Anecdotal evidence suggests environmental footprint or 'greenness' is increasingly one of the factors women consider when choosing a method , thus the development of additional non-hormonal methods will provide women for whom this is a factor with more options.

Submitted by Kate Ryan on June 10, 2011 at 2:10 PM
The National Women's Health Network and the Reproductive Health Technologies Project would also like to highlight our support for NICHD's intention to evaluate the interaction of genetics, epigenetics, environment, behaviors and socioeconomic status, as well as their impact on human reproductive development. However, we also feel that there are gaps in NICHD's intended areas of study - notably the absence of sexuality as a factor. In a paper published recently by the Guttmacher Institute, Sneha Barot wrote that "...sexuality may be the most underdeveloped area of sexual and reproductive health research, including fundamental questions such as what constitutes "sexual health" and how to achieve it. " We agree, and we strongly urge NICHD to include research on healthy sexuality and sexual identity as a scientific priority over the next decade.

We support NICHD's efforts to advance reproductive science, which will enable the Institute to achieve this ambitious ten year agenda. It is essential that NICHD establish fellowships and training grants targeted to contraceptive development. A renewed focus on this area of research is essential to the creation of novel contraceptive methods, compounds and delivery systems for both women and men. We also support the development of innovative and educational training programs between academia, government, foundations, industry, NGOs, and advocacy organizations. Collaboration across the various reproductive fields is vital to approaching this research in a new way. We appreciate the inclusion of advocacy organizations in this new paradigm of reproductive health research and look forward to the opportunity to ensure that the voices of women consumers are heard and their perspectives and priorities are fully considered throughout the Institute's contraceptive R&D process.

Submitted by Kate Ryan on June 10, 2011 at 2:10 PM
On behalf of the Guttmacher Institute, thank you for the opportunity to comment on the NICHD Vision process. Our comments are limited to two aspects of the White Paper:

First, we applaud the attention given to unintended pregnancy. We think it would help readers of this document, who come from a variety of disciplines and backgrounds, if a short definition of unintended pregnancy were provided. Unintended pregnancy includes pregnancies that are mistimed (usually occurring too early) or unwanted (no desired at any time). Standard definitions of unintended pregnancy also include those that occurred later than a woman wanted, suggesting that efforts to address infertility issues are also appropriate.

Second, NICHD's support for innovative contraceptive research is crucial for efforts to reduce the burden of unintended pregnancies and improve maternal and child health. Through its investment in contraceptive evaluation research, NICHD plays a key leadership role in ensuring acceptability and effective use of existing products in various settings and populations and in addressing behavioral issues related to fertility and contraceptive use. The Institute's investment in contraceptive development research is critical for producing new contraceptive modalities that offer couples options with fewer side-effects and additional non-contraceptive health benefits. Specific opportunities and research priorities in the area of contraceptive development include the need for non-hormonal contraception, post-coital contraception and multipurpose prevention technologies that would prevent both pregnancy and sexually transmitted infections (STIs). This latter issue is particularly relevant to a concern with reproduction, given the negative consequences of STIs for reproductive capacity. Non-use of contraception among women at risk of unintended pregnancy remains a key concern; about half of unintended pregnancies occur to the 10% of women using no contraception.

Submitted by Heather Boonstra on June 10, 2011 at 3:06 PM
I agree with the NICHD vision that studying the developmental origins of reproductive disease/disorders is important, as is gaining a better understanding of how "normal" reproductive function develops (during prenatal, postnatal, and pubertal periods). Indeed, it is difficult to study developmental impairments leading to disorders/disease if the specific mechanisms/patterns underlying normal reproductive development are not first well-understood. This is particularly true for postnatal development and puberty, for which many of the key regulatory mechanisms are still not well understood, making the study of pubertal disorders challenging.

Second, while the importance of studying behavior cannot be disputed, physiological studies (i.e., focusing on physiological mechanisms in and between reproductive tissues, from brain to pituitary to gonad) cannot be overlooked. The importance of studying physiology (both at the basic science level as well as translational/clinical) is fundamental for understanding normal reproductive mechanisms, both developmental and regulatory. Understanding physiology and developmental/regulatory mechanisms will also have important implications for understanding (and treating) impaired biological mechanisms that underlie reproductive disorders/disease.

Lastly, I would also echo other researchers' comments regarding emphasis on human and non-human primate work. While human and non-human primate work is indeed critical, non-primate animal models are also absolutely necessary, and have proven to be extremely valuable for efficiently (and often cheaply) understanding many of the key cellular, molecular, and physiological mechanisms relating to puberty, sexual maturation, and various features of adulthood fertility.

Submitted by Sasha Kauffman on June 10, 2011 at 4:41 PM
One area of reproductive biology that must not be overlooked as investigators strive for innovation and novelty in their grant applications is the study of non-human primates (NHPs): a genetically intractable model. This is because there are marked species differences in the control of many reproductive processes. One example is provided to illustrate, namely, the control of ovulation. Since the discovery that mutations of the kisspeptin receptor (GPR54) were associated with hypogonadotropic hypogonadism and delayed/absent puberty, kisspeptinocentric views of the control of GnRH are justifiable emerging. In the context of ovulation, elegant studies of rodent models across the globe have led to a schemata for the preovulatory LH surge, in which the action of positive feedback action of estradiol (E2) to stimulate LH release is exerted on kisspeptin neurons in the rostral hypothalamus. The resulting GnRH surge triggers the preovulatory LH discharge, that in turn results in ovulation. Ironically, in this era of NIH's focus on translational research, the foregoing model of the neuroendocrine control of ovulation is of unlcear relevance to the human female. Extant evidence indicates that women ovulate without a GnRH surge; all that is involved is pulsatile GnRH secretion, with the positive feedback action of E2 being exerted at the pituitary level, not the hypothalamus. The role of kisspeptin and related peptides (neurokinin B and dynorphin) in the control of ovulation in NHP models has not been studied. There is not a single laboratory worldwide that is systematically examining the neurobiological control of the menstrual cycle using NHPs. The problem is exacerbated by the fact that current leaders in this and other areas of primate reproduction represent a largely graying generation. This also impacts upon NIH Review Groups where expertise in NHP reproduction is already minimal. That a solution will emerge from the National Primate Research Centers (NPRC) is unlikely. In the most recent guidelines issued by NCRR, it is stated that "Staff scientists will not be reviewed by merit of funding outside the P51, rather by contributions to the mission of the NPRC, including administrative duties, interactions with affiliate and visiting scientists and other relevant activities." Clearly, NCRR don't want their primatologists to be conceptual leaders, but rather supporting scientists that function as a core resource to implement experimental ideas of others.

Submitted by Tony Plant on June 10, 2011 at 5:34 PM
As someone with ongoing research projects in this area, I read the white paper on reproduction with interest. However, I think there is an important contributor to reproductive health and disease that is overlooked here, the role of individual choice and financial incentives. This is an area where social scientists in general and economists in particular have made contributions to the study of reproduction, both in bringing sophisticated statistical techniques and in recognizing and quantifying the role of individual choice and constraints in determining fertility and health. For example, the work of economists (including my own) has looked at the role of health insurance coverage for infertility treatment on use of infertility treatment, age at first birth, the multiple birth rate and health outcomes of multiples, finding an important role for increased coverage in increasing use of infertility treatment, age at first birth, and the multiple birth rate; and also in affecting infant health. To take another example, the discussion of contraception mentions behavioral issues and insuring effective use, yet there is little discussion in the white paper of the role of individual choice and tradeoffs in affecting contraceptive use. Economists could inform this agenda by incorporating their perspectives and methods. Non-use of contraception is not simply the result of misperceptions about the probabilities of conceiving, but also reflects individual attitudes towards risk and the discomfort and cost of using contraception. To take another example, the discussion of pre/peri- conceptual health and pregnancy establishment discusses data needs, yet omits discussing the fact that couples are timing their attempts at childbearing by trading off costs and benefits given their understanding of their own health and likelihood of successful reproduction. Age at first birth has increased considerably over recent decades in part due to changes in family formation and women's increased labor force participation, and this undoubtedly has influenced maternal and paternal health at pre- and peri- conception. Data collection intended to inform our understanding of the effect of being born after use of ART or infertility treatment should help ensure that the role of individual's economic conditions and the health care system can also be studied. Restricting data collection to ART/treatment users may give misleading findings due to selection into use of ART/treatment.

Submitted by Marianne Bitler on June 10, 2011 at 6:04 PM

The period for commenting on NICHD scientific Vision white papers is now closed.

Last Updated Date: 06/04/2012