Research Priorities

Childhood and adolescent beginnings to gynecologic conditions

  1. Lichen sclerosus: Lichen sclerosus et atrophicus (LS&A) is a recognized vulvar dermatologic condition in children and post-menopausal women. This disease is associated with significant morbidity including vulvar itching, long term scarring and vulvar cancer. Very little research has been conducted in the pediatric population to evaluate the origins, best treatment and long term outcomes of this condition. A recent pilot study performed by our team reveals that the microbiome in the stool of girls with LS&A differs from that of girls with nonspecific vulvovaginitis and those without dermatologic findings (manuscript submitted). Further study on this condition in children may impact long term outcomes in women during their reproductive age and beyond.
  2. Innate Immunity of the adolescent genital tract and its impact of infectious disease acquisition: Adolescents are disproportionately affected by sexually transmitted infections, including HIV. In addition, early age of coitarche is associated with an increase in cervical cancer which in turn is associated with human papilloma infection. The innate immunity of the adolescent lower reproductive system may account for these differences. We have conducted an innovative pilot study to compare immune markers of the lower genital tract of sexually active and non-sexually active adolescents which revealed that sexually active adolescents were more likely to have immune biomarkers which are protective against HIV than their non-sexually active counterparts (Am J Reprod Immunol. 2018 Jun;79(6):e12846.) We are now completing a study to evaluate the effects of different hormonal contraceptives on the immune markers and microbiome of the lower genital tract in adolescents. Such research may allow us to develop innovative interventions which may decrease the infectious disease burthen on the reproductive tract of women.
  3. Future Opportunities:
    1. Idiopathic premature ovarian insufficiency (POI): Although certain conditions such as Turner Syndrome, galactosemia and FMR 1 mutations are known to be associated with POI, for a large majority of young girls with POI a cause can not be elucidated. In addition, evidence based clinical evaluation and management is lacking. A multicenter retrospective review reveals that this is a rare condition (J Pediatr Adolesc Gynecol. 2018 Dec;31(6):597-604).
    2. Polycystic ovary syndrome (PCOS): PCOS is the most common endocrine disorder in women and has serious consequences including infertility, metabolic and cancer risks. Puberty mimics many of the hallmarks of PCOS and the diagnosis and treatment of PCOS is very controversial in this age group. (Horm Res Paediatr. 2015 Apr 1. PMID 25833060). Elucidation of diagnostic markers, risks of specific phenotype on long term morbidity as well as possible interventions in the adolescent period would have significant public health impact. markers of PCOS compared to non-PCOS adolescents. Future collaborations with researchers in the field of pediatric endocrinology, adolescent medicine and PAG may allow us to begin to answer some of these questions
    3. Pelvic pain/endometriosis: is a significant burden in the healthcare system. Many pain conditions including endometriosis appear in the adolescent period. Thorough evaluation of the natural history, underlying physiology, as well as the impact of various modalities of treatment in the adolescent may also have a significant impact on a large population of adult women with these conditions.

Fertility Preservation

 In 2012 the PAG program at Children’s National in collaboration with the Oncofertility Consortium began to perform ovarian tissue cryopreservation (OTC) for girls undergoing gonadotoxic therapy. In addition, as members of the Pediatric Initiative Network of the Oncofertility Consortium, we have created databases to evaluate long term outcomes of individuals who have undergone OTC. This unique program will allow for innovative research regarding fertility preservation in children and adolescents including conditions associated with premature ovarian insufficiency not related to gonadotoxic therapy such as Turner syndrome and galactosemia. A unique collaboration between the Oncofertility Consortium, Children’s National and NICHD will allow a platform to conduct research which will advance this field.

Rare Conditions: Implication for Human Health

Rare conditions can give us unique insight into human health. Unusual gynecologic tumors in pediatric and adolescent gynecology have been linked to specific genes and such knowledge may allow deeper understanding of tumor development in the future  (J Pediatr Adolesc Gynecol. 2017 Aug;30(4):495-498). Other rare conditions which can cause differences in sex development are often associated with single gene defects. Study of the effects of these gene abnormalities in general health of affected individuals will allow us to better care for them as well as elucidate possible mechanisms of disease in other populations. The NICHD and Children's National program have partnered with the NIH funded Disorders of Sex Development-Translational Research Network. This unique collaboration will allow for cutting edge research in these rare conditions.

Gynecologic Care in Women with rare conditions

Often rare genetic conditions are well studied in childhood and little is known about long term implications of these. We have to date conducted research with other NIH investigators regarding gynecologic outcomes in women with McCune Albright Syndrome (Orphanet J Rare Dis. 2019 Apr 29;14(1):90.) and congenital adrenal hyperplasia. Such research will allow us to counsel and provide better care for these individuals.

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