Research

Research Priorities

1. Female Fertility Preservation

Fertility preservation includes procedures used to help keep a person's ability to have children. These may give patients with cancer or other rare disorders that affect fertility the opportunity to possibly have biological children in the future, which may also improve their quality of life. Ovarian Tissue Cryopreservation (OTC) is a surgical procedure in which part, or a whole ovary is removed. The tissue, which contains immature eggs, is frozen and stored. Later in life, the tissue may be re-implanted inside the body for future fertility. In December 2019, the American Society of Reproductive Medicine Committee Opinion external link on fertility preservation in patients undergoing gonadotoxic therapies stated that OTC should be considered an established medical procedure and is no longer considered experimental. However there remain significant gaps in knowledge regarding OTC for fertility preservation in children and adolescents receiving gonadotoxic therapy as the fertility effect of gonadotoxic therapy as well as the fertility benefits of OTC cannot be ascertained until 5 to 30 years after therapy. Even less is known about OTC in patients with diminished ovarian reserve or premature ovarian insufficiency due to causes that are not due to gonadotoxic agents such as chromosomal abnormalities or genetic mutations.

At the NICHD-PAG, we have been involved in research through the Oncofertility Consortium external link and have had an ovarian tissue cryopreservation (OTC) protocol for girls receiving gonadotoxic therapies (chemotherapy and radiation therapy) at Children's National Hospital since 2012.

We work closely with the Reproductive Endocrinology and Infertility Division and refer patients who qualify to their Evaluation of Women and Men with Endocrine and Reproductive-Related Conditions Protocol that offers oocyte cryopreservation services (Protocol #99-CH-0103: https://clinicalstudies.info.nih.gov/protocoldetails.aspx?id=99-CH-0103&&query=)

Our team at NICHD is involved in several projects which will advance the field of oncofertility and fertility preservation in special populations, such as Turner Syndrome, Galactosemia, adolescent premature ovarian insufficiency.

2. Profiling of the Human Ovary

The normal human ovary is not clearly understood as under normal healthy circumstances ovarian tissue would not be removed or biopsied. Ovarian tissue cryopreservation has allowed the opportunity to study human ovarian tissue and obtain a “snapshot” regarding histology and function. Through our ovarian tissue bank (which contains over 100 specimens of pediatric, adolescent, and young adult ovarian tissue), the PAG lab is involved in several projects that will further define ovarian histology and function.

  • Creating a single cell transcriptomic atlas of human ovarian tissue
    Using 10X Visium spatial and single cell data, the NICHD PAG lab is performing spatial transcriptomic analysis of the human ovary from early childhood to young adulthood and identifying the key regulatory network of transcription factors [REGULON] and their target genes that are responsible for primordial follicle dormancy/activation and follicular growth. This single cell and spatial transcriptomic profiling of ovarian tissue from adult donor, children, and adolescent girls with different conditions such as cancer prior to chemotherapy, prepubertal girls with galactosemia and Turner syndrome will further the understanding of molecular mechanisms leading to primary ovarian insufficiency (POI).
  • NICHD/Oncofertility Ovarian Tissue Slide Image Databank
    A digital ovarian tissue slide image database of H&E-stained ovarian and gondal tissue slides from individuals who have undergone OTC or prophylactic gonadectomy in cases of variations of sex characteristics. This digital slide database contains slides linked to clinical data from over 400 pediatric and young adult ovaries and is accessible to scientists intramurally and extramurally both nationally and internationally.
  • NICHD Ovarian Nomenclature Workshop 2021
    Experts in reproductive endocrinology, gynecologic oncology, radiology, pathology, bioinformatics, and ovarian tissue research, met and created workgroups to further delineate ovarian follicle description, tissue ontology, and the 3-D description of the ovary.
  • Publications

3. Childhood and Adolescent Beginnings of Gynecologic Conditions

Endometriosis is a condition in which tissue similar to the lining of the uterus grows in other places in the body and can cause significant pain. Polycystic Ovary Syndrome (PCOS) is a set of symptoms related to a hormonal imbalance resulting in irregular periods, excessive hair growth, severe acne, infertility which can result in long term consequences including diabetes, metabolic syndrome, and uterine cancer. Lichen sclerosus is a skin condition which has been mostly studies in post-menopausal women but also affects children. All of these conditions begin during the childhood or adolescent period and are associated with significant health problems and impact quality of life. However, the study of these conditions has predominantly been done in adult populations. Pediatric and adolescent population-based studies to evaluate the beginnings of these conditions may elucidate possible early diagnosis and intervention, treatment, and prevention.

3. Rare Gynecologic Conditions: Implications for Human Health

The study of rare conditions often can elucidate unique physiology that affect human health and development. We have developed protocols to study several conditions encountered in PAG which are detailed below.

4. Rare Diseases with Associated Gynecologic Conditions

Individuals with rare diseases often have significant gynecologic impact from their underlying conditions. Gynecologic conditions throughout the reproductive span in individuals with rare conditions will be evaluated in Data Collection Study of Pediatric and Adolescent Gynecology Conditions listed above.

Examples of collaboration with other NIH teams in research on gynecologic conditions in individuals with rare conditions:

  • Fibrous dysplasia/McCune Albright Syndrome (FD/MAS)- Michael Collins, MD, NIDCR- MAS is caused by a somatic mutation that can be present in the ovary and cause spontaneous activation of ovarian function and precocious puberty. We conducted a phone interview of all women in the FD/MAS study and asked about OB/GYN history. Currently we are working with the FD/MAS investigators to evaluate bleeding and pain symptoms after menarche, obstetrical outcomes, fertility, and age of menopause.
  • Congenital Adrenal Hyperplasia (CAH)- Deborah Merke, MD, MS- Women with excess androgen conditions have significant gynecologic impact from their underlying endocrine disorder. We have conducted a case control study of sexual function and quality of life in women with CAH compared to age, race, and marital status matched controls. Based on these results we are evaluating interventional studies to improve sexual function.
  • Publications
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