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Fertility and Infertility Branch (FIB)

Fertilization

Overview/Mission

FIB's mission is to encourage, enable, and support research aimed at understanding the processes that underlie human reproduction, uncovering causes of infertility, and pursuing novel paths to improve fertility outcomes for infertile patients, as well as foster training in these areas to strengthen the next generation of researchers. To this end, FIB funds basic, clinical, and translational studies to enhance our understanding of typical 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 male and female fertility. The Branch therefore occupies a broad scientific space spanning discovery of reproductive mechanisms, understanding reproductive dysfunction, identification of diagnostic or therapeutic targets, development and testing of interventions, and improved approaches to fertility management, preservation, and control.

  • Fertility Preservation: Supports basic, clinical, and translational research to preserve and protect reproductive capacity in individuals who are likely to become infertile and develop approaches to restore fertility after damage.
  • Male Reproductive Health: Supports fundamental, translational and clinical research on the physiology and pathophysiology of male reproduction.
  • Ovarian Function and Dysfunction: Supports fundamental studies of early developmental mechanisms as well as translational and clinical research aimed at improving the assessment and management of reproductive and early embryonic developmental problems.
  • Embryonic Gonad and Germ Cell Development: Supports fundamental research on embryonic development of the germ cells and gonads and the interaction of germ cells with the somatic cells of the testis and ovary throughout development.
  • Reproductive Medicine Infertility: Studies etiology and pathophysiology of diseases and disorders that cause human infertility and impaired fecundity.
  • Reproductive Neuroendocrinology: Supports research on hypothalamo-pituitary-gonadal axis, the neural circuits and hormonal feedback systems controlling reproductive function.
  • Uterine Function and Implantation Biology: Supports basic, translational, and clinically relevant research on endometrial biology, uterine remodeling, hormonal regulation, embryo-endometrial communication, implantation and the establishment of the maternal environment required for successful reproduction.
  • Product Development to Address Infertility: Supports translational research to innovate existing or develop novel technologies designed to improve fertility outcomes or reduce costs associated with assisted reproductive technologies.
  • 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.
  • Clinical Reproductive Scientist Training (CREST) Program: Supports, in partnership with American Society for Reproductive Medicine, training of reproductive endocrinology and infertility specialists to conduct 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.

  • Data and Specimen Repository: Stores data and specimens of completed RMN trials, including Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation, Pregnancy in Polycystic Ovary Syndrome (PPCOS) I, PPCOS II, and Efficiency of the Superovulation and Intrauterine Insemination in the treatment of fertility, for use in other research

  • University of Virginia Ligand Assay and Analysis Core: Provides high-quality and cost-effective assay services
  • Interlome Gene List: This gene variant database presents NICHD-funded research on pathogenic variants of human genes that are associated with fetal lethality, spontaneous pregnancy loss, recurrent pregnancy loss, intrauterine fetal demise, stillbirth, and neonatal mortality.
  • Recurrent Pregnancy Loss Data Sets: This -omics data repository presents NICHD-funded research on recurrent pregnancy loss. It integrates genetic, clinical, and molecular phenotypic data to discover novel genes and genetic variants that contribute to pregnancy loss and to improve prediction of the loss.

  • Daniel Johnston, Ph.D., Branch Chief
    Main Research Areas: Epididymis; sperm; testis; contraception; Early pregnancy loss and recurrent pregnancy loss
  • Luis Dettin, Ph.D., Program Officer
    Main Research Areas: Cellular, molecular, genetic, and epigenetic mechanisms that regulate neuroendocrine control of reproduction across the lifespan; gonadotropin-releasing hormone (GnRH) secretion; gonadotropin regulation; neuroendocrine-immune interactions; gametogenesis; ovulation; sexual behavior; influence of metabolic signals on reproductive function.
  • Emily Jay, Staff Assistant
  • Travis Kent, Ph.D., Program Officer
    Main Research Areas: Spermatogenesis; testis biology; sperm function; male reproductive tract (including epididymis and seminal vesicles); semen biology; fertilization; sperm/semen contribution to offspring fitness; NCTRI; infertility product development
  • Christopher C. Lindsey, Ph.D., Program Officer
    Main Research Areas: Product development; ion channels of the reproductive system.
  • Ying Liu, Ph.D., Program Officer
    Main Research Areas: Uterine function and implantation biology, including the female reproductive tract (oviduct, uterus, and vagina); blastocyst implantation; trophoblast-uterine interactions; trophoblastic differentiation; and reproductive immunology. 
  • Ebony Parham, Extramural Staff Assistant
  • Ravi Ravindranath, Ph.D., Program Officer
    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, Ph.D., Deputy Branch Chief and Program Officer
    Main Research Areas: Genetic and epigenetic control of early germ cell development and meiosis; fertility preservation; ovarian function and dysfunction; primary ovarian insufficiency; fertility status and overall health; sex determination and differentiation (in the context of fertility and infertility); training for graduate students and postdoctoral fellows in reproductive health

Highlights

Development of Novel or Improved Infertility Technologies Request for Applications 
NICHD has published a NOFO to support and facilitate multidisciplinary research approaches for the development or improvement of technologies - including drugs, devices, products, or clinical practices - designed to improve fertility outcomes in patients dealing with infertility, particularly in the context of assisted reproductive technologies (ART). This NOFO aims to position innovative and validated technologies for future clinical development.

  • RFA-HD-26-001: Development of Novel or Improved Infertility Technologies (R61/R33 Clinical Trial Optional)

Uterine Fibroids and Women’s Health. Learn about NICHD support of research on uterine fibroids and women's health, and review some recent advances in understanding, diagnosing, and treating them.

Assisted Reproductive Technology (ART) and Women's Health. Learn about NICHD support of research on ART and women's health, and review some recent advances in advancing ART methods, achieving optimal conditions for ART, and understanding its long-term effects.

Polycystic Ovary Syndrome (PCOS) and Women's Health. Learn about NICHD support of research on PCOS and women's health, and review some recent advances in understanding, diagnosing, and treating this condition.

Infertility and Women's Health. Learn about NICHD support of research on infertility and learn about some recent advances in understanding, diagnosing, and treating this common condition in males and females.

Endometriosis and Women's Health. Learn about NICHD support of research on endometriosis and learn about some recent advances in understanding, diagnosing, and treating this common gynecologic condition.

Get to Know NICHD! Learn more about what inspired FIB Acting Chief Dr. Daniel Johnston and Program Officer Dr. Travis Kent to pursue science and how their decisions and experiences led them to their careers with NICHD.

Workshop on Idiopathic/Non-Aneuploid Early Pregnancy Loss (EPL): The State of the Science. This workshop, held July 22-23, 2021, included discussions of knowledge gaps, barriers to advancing the science, promising approaches, and needed tools for EPL research. Access recordings from Day 1 and Day 2, or the workshop program (PDF 160 KB) for additional information.

Physiomimetics and Organoids for Reproductive Health. This workshop, held September 23-24, 2021, focused on physiomimetics, sometimes called “organs-on-a-chip,” and organoids, and applications of these technologies for reproductive health research. Access recordings from Day 1 and Day 2, or the meeting summary (PDF 469 KB) for additional information.

Advancing Bioprinting and Regenerative Medicine Solutions for Obstetric, Gynecologic, and Pediatric Applications Workshop. This workshop, held November 16-17, 2021, was a transdisciplinary discussion on the state-of-the-science of tissue-construct manufacturing using 3D printing of biological, cellular, and tissue-based products (a.k.a., bioprinting) and regenerative medicine in the context of obstetric, gynecologic, and pediatric applications. Access recordings from Day 1 and Day 2.

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

  • Gene variant involved in genome integrity and male infertility. Even though male infertility affects millions of couples, the cause of primary infertility in males remains largely unknown. In a genomic study of spermatogenic failure, FIB-funded scientists from the GEnetics of Male INfertility Initiative identified single nucleotide variants (SNVs) in germ-cell nuclear antigen (GCNA), a gene on the X chromosome critical for genome integrity in male meiosis. All the identified SNVs had an extremely low minor allele frequency in the general population but were found in 7 men with spermatogenic failure in the cohort of approximately 2,200 participants. Five identified SNVs occur in key functional regions, suggesting that they disrupt structure and function of the GCNA protein, ultimately arresting germ-cell division. This is the first study implicating GCNA, a key genome integrity factor, in human male infertility. (PMID: 33963445)
  • New in vitro system for mammalian meiosis. Despite conservation from yeast to humans of the chromosome structures and the fundamental molecules involved in meiosis, the trigger for meiosis differs across species, and for humans, is still unknown. In yeast, nutrient deprivation triggers meiosis; in mammals, retinoic acid (RA) and its downstream targets, while necessary for meiosis, are not sufficient to trigger it. This knowledge gap prevented scientists from initiating mammalian meiosis and spermatogenesis in vitro. In this FIB-funded study, Dr. Ning Wang and colleagues showed that nutrient deprivation plus RA, but neither alone, induced meiosis in primary mouse spermatocytes cultured without somatic cells. The combination induced both the expression of meiosis-specific genes and DNA double strand breaks. Switching these induced cells to a "meiotic progression" medium allowed them to develop to the early pachytene stage, and to form chromosomal synapses. Transcriptomic analysis of the nutrient-deprived cells identified 11 transcription factor genes that were upregulated, and associated with early meiosis in vivo, independently of RA. In addition to identifying key players in meiotic initiation, this work also establishes a valuable in vitro system for studying meiosis and producing male haploid gametes. (PMID: 33741948)
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