Fertility and Infertility Branch (FIB)

FIBOverview/Mission

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.

Reproductive Transitions

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.

  • 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
  • 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
  • Koji Yoshinaga, Program Director
    Main Research Areas: Female reproductive tract (oviduct, uterus, vagina); endometrial function and implantation biology; immune cell participation in establishment and maintenance of pregnancy; mechanisms of action of hormones, cytokines, and growth factors

Highlights

Some recent findings from FIB-supported researchers include the following:

  • 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)
  • Small non-coding RNAs (sncRNA) in sperm can mediate intergenerational transmission of paternally acquired phenotypes. Dr. Chen and his colleagues showed that sncRNAs encode essential paternal information, which—after fertilization—could be responsible for phenotypes such as mental stress and metabolic disorders in the next generation. (PMID: 29695786 )
  • 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)
  • Pregnancy Intervals linked to babies' health. In a study of women who had had a previous successful pregnancy, Dr. Su and her colleagues found that an interval of less than 12 months or greater than 5 years until the next pregnancy was associated with the highest risk of adverse outcomes for the newborns. (PMID: 29778383)
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