The mission of FIB is to encourage, enable, and support research aimed at alleviating human infertility, uncovering new possible pathways to control fertility, and expanding fundamental knowledge of processes that underlie human reproduction. To this end, FIB funds basic, clinical, and translational studies to enhance our understanding of normal reproduction and reproductive pathophysiology, as well as to enable the development of more effective strategies for the diagnosis, management, and prevention of conditions that compromise fertility.
Early Pregnancy Loss
Gap: Although early miscarriage is a serious issue, very little is known about its causes and consequences. Only about 50% of conceptions advance beyond 20 weeks of gestation. Approximately 50% to 70% of these early pregnancy losses result from lethal numeric chromosome errors (i.e., aneuploidy), which impact various aspects of pregnancy establishment, such as implantation and early placentation.
Priority: Encourage studies of gamete quality and preplacental processes as they relate to the etiology of early pregnancy loss.
Epigenetics and Reproduction
Gap: Epigenetic modifications to the genome occur during gametogenesis and preimplantation embryonic development. Researchers are just beginning to understand how these modifications occur and the impact of absent or altered modifications to offspring health. Data are also emerging to suggest that maternal and lifestyle behaviors (e.g., nutrition, drug use, physical activity) can alter the genome through epigenetic mechanisms and affect the offspring of future generations.
Priority: Identify critical windows for epigenetic alteration of reproductive processes and the mechanisms of transgenerational inheritance.
Fertility Status as a Marker of Overall Health
Gap: Evidence over the past decade indicate that an individual's fertility status is associated with an increased risk of developing chronic health conditions, such as cancer, diabetes, cardiovascular disease, and metabolic dysfunction. One study documented an association between shorter life spans and an infertility diagnosis for a cohort of men recruited from Texas and California. Additional work is needed to understand this link for infertile men and women and to begin to investigate the possible biological basis for this association.
Priority: Support studies that investigate fertility status as a marker of overall health for both men and women.
Genetic Basis of Idiopathic Infertility
Gap: Many cases of infertility cannot be ascribed to a specific genetic cause. Knowing the genetic basis of infertility is critical, not only for eventually treating infertile couples, but also for evaluating the risk that the condition will be passed to their offspring.
Priority: Encourage studies that help elucidate the genetic basis of idiopathic male and female infertility.
Metabolism, Nutrition, and Reproduction
Gap: The impact of nutrition on reproductive function is well established, with evidence that under- and overeating can negatively influence fertility in men and women. One likely way that nutritional modification alters reproduction is by affecting metabolic function. In turn, altered metabolism has profound effects on reproduction, highlighted by conditions such as insulin resistance, diabetes, and gestational diabetes. Recent attention in the field has focused on the effects of nutrition on the microbiome and on the role of the microbiome in regulating metabolism.
Priority: Support research that examines metabolic and nutritional regulation of fertility, with emphasis on the role(s) of the microbiome.
Gap: The reproductive system is unique in that it undergoes profound functional and structural changes at different points in the normal lifespan, yet strong indicators of the onset or completion of those changes are lacking. Longitudinal studies to identify novel markers of sexual development and reproductive aging are critical to distinguish normal transitional development from atypical development. Identifying potential problems with fertility or diagnosing reproductive diseases and disorders that can impact fertility at an earlier age, thereby allowing earlier prevention or treatment strategies.
Priority: Identify reliable biomarkers to study reproductive transitions across the male and female lifespans, including puberty and reproductive aging.
Technology and Models for Infertility and Fertility Preservation
Gap: Current technical barriers and a lack of appropriate experimental models limit the ability to study the causes of infertility or how to preserve fertility when it is threatened.
Priority: Encourage the development of innovative technologies and model systems to study fertility and infertility, as well as preservation of fertility.
- Fertility Preservation: Supports basic, clinical, and translational research designed to preserve reproductive capacity in individuals who are or may become infertile
- Male Reproductive Health: Supports research on the physiology and pathophysiology of male reproduction
- Ovarian Function and Dysfunction: Supports research on the function of the ovary
- Preimplantation Genetics and Development: Studies the genetic and epigenetic control mechanisms that affect the quality of oocytes and preimplantation embryos
- Embryonic Gonad and Germ Cell Development: Examines embryonic development of the gonads and germ cells
- Reproductive Medicine Infertility: Studies etiology and pathophysiology of diseases and disorders that cause human infertility and impaired fecundity
- Reproductive Neuroendocrinology: Addresses the central neurobiological mechanisms governing gametogenesis and ovulation
- Uterine Function and Implantation Biology: Supports basic research studies on uterine function involving molecular-, cellular-, tissue-, and organ-level approaches
- Dual Purpose with Dual Benefit: Research in Biomedicine and Agriculture Using Agriculturally Important Domestic Animal Species (An Interagency Partnership): Promotes the use of agriculturally important domestic animal species in basic and translational research relevant to both biomedicine and agriculture
- National Centers for Translational Research in Reproduction and Infertility (NCTRI): Promotes multidisciplinary interactions between basic and clinical scientists interested in establishing high-quality translational research programs in the reproductive sciences
- Reproductive Medicine Network (RMN): Conducts large, multicenter clinical trials of diagnostic and therapeutic interventions for male and female infertility and reproductive diseases and disorders
- Clinical Reproductive Scientist Training (CREST) Program: In partnership with American Society for Reproductive Medicine, trains reproductive endocrinology and infertility specialists in the conduct of clinical research
- Reproductive Scientist Development Program (RSDP): Develops a cadre of reproductive physician-scientists based in academic departments to address important problems in the field of obstetrics and gynecology
- Now in NICHD's Data and Specimen Hub (DASH): Reproductive Medicine Network Data
- Human Endometrial Tissue and DNA Bank : Collects and stores human endometrial tissue and DNA from well-characterized clinical subjects and distributes items to researchers
- Human Placental Tissue Bank : Collects and stores human placental tissue from well-characterized clinical specimens for use by researchers
- Ovarian Kaleidoscope Database : Provides information regarding the biological function, expression pattern and regulation of genes expressed in the ovary
- University of Virginia Ligand Assay and Analysis Core : Provides high-quality and cost-effective assay services
- Reproductive Medicine Network (RMN) Data and Specimen Repository : Stores data and specimens of completed RMN trials that may be used by researchers
- Teede, HJ, Misso, ML, Costello, MF, Dokras, A, Laven, J, Piltonen, T, Normal, RJ, and the International PCOS Network. (2018). Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Clinical Endocrinology (Oxf), July 19. PMID: 30024653. The full text of the guideline is available at https://www.monash.edu/medicine/sphpm/mchri/pcos/guideline .
- Louis DePaolo, Branch Chief
Main Research Areas: Clinical Reproductive Scientists Training Program; Reproductive Scientist Development Program; translational research in reproduction
- Esther Eisenberg, Program Director and Project Scientist
Main Research Areas: Assisted Reproductive Technology; reproductive medicine and infertility (includes infertility disorders and reproductive disorders that impact fertility such as endometriosis); Reproductive Medicine Network; polycystic ovary syndrome; female reproductive tract (oviduct, uterus, vagina); endometrial function and implantation biology
- Stuart Moss, Program Director
Main Research Areas: Male reproductive health (includes testis biology, sperm development and function, and hormone production); fertility and infertility: translational research centers
- Ravi Ravindranath, Program Director
Main Research Areas: Totipotent and pluripotent stem cells; embryonic and induced pluripotent stem cells; reprogramming; oocyte quality and developmental competence; genetics and epigenetics of preimplantation embryo; reproductive neuroendocrinology; gonadotropins; metabolic signals and reproduction; reproductive behavior
- Susan Taymans, Program Director
Main Research Areas: Genetic and epigenetic control of early germ cell development and meiosis; fertility preservation; ovarian function and dysfunction; primary ovarian insufficiency; sex determination and differentiation (in the context of fertility and infertility); training for graduate students and postdoctoral fellows in reproductive health
Some recent findings from FIB-supported researchers include the following:
- New factors identified in ovarian primordial follicle survival. Work from Dr. Joan Jorgensen’s laboratory shows that expression patterns of transcription factors Irx3 and Irx5 are critical in establishing the connections between oocytes and their surrounding somatic cells during primordial follicle formation. Defects in this patterning disrupt communication between the two cell types and result in oocyte death, potentially shortening the span of a woman’s fertile reproductive years. (PMID: 30071018)
- Epigenetic changes in ADAMTS linked to preterm birth. Dr. Mainigi and colleagues studied placentas from a population of women at high risk for preterm birth. Their research showed that regulation of methylation levels of members of the gene family ADAMTS, implicated in cell invasion and migration, is important in regulating early placentation and later susceptibility to preterm birth. (PMID: 30239759)
- Single-cell transcriptomes yield information on spermatogonial stem cells to spermatids. Dr. McCarrey and his colleagues performed single-cell transcriptomics of more than 62,000 spermatogenic cells from mice and humans and identified unique three-gene expression signatures for 11 different spermatogenic cells types. Among other uses, this comprehensive gene expression roadmap can help optimize protocols for in vitro spermatogenesis. (PMID: 30404016)
- Hyperandrogenemia and obesity have detrimental effects on fertility and gestation in primates, which may be directly relevant to women with polycystic ovary syndrome (PCOS). Dr. True and her colleagues showed that, in a non-human primate model, elevated testosterone in females increased the time to achieve pregnancy, while a western-style diet (WSD) reduced fertility. The combination of testosterone and a WSD additionally impaired glucose tolerance and caused pregnancy loss. (PMID: 29401269)
- Major depression and antidepressant use affect male and female fertility. A study of major depression in couples with infertility showed that currently active major depression in infertile men can lower chances of pregnancy, and use of non-selective serotonin reuptake inhibitor antidepressants in infertile women could be linked to first-trimester pregnancy loss. (PMCID: PMC5973807)