Site:  University of Pennsylvania

Principal Investigator:  Clarisa Gracia, MD

Rationale

There are currently over 250,000 survivors of childhood cancer in the U.S.  While recent advances in therapeutic technologies have led to an increase in cancer survivorship, these powerful therapies may also lead to impaired fertility and premature ovarian insufficiency.  While reduced reproductive potential is well documented in adolescents and young adults with cancer, little is known about these patients’ hypothalamic-pituitary-gonadal function prior to, during, and after treatment.  And though serum hormone and ultrasound measures are routinely used as surrogate markers of fertility in adult women prior to and after treatment, they have yet to be validated in pediatric cancer patients.  

This project aims to develop means for early detection of decreased fertility potential in order to identify individuals who would benefit from application of existing assisted reproductive technologies and/or emerging novel fertility preserving methods such as ovarian tissue cryopreservation.  The results from this project will serve as preliminary data for the establishment of a long-term cohort study of pediatric cancer survivors to examine the association between ovarian function measures, pregnancy rates, pregnancy outcomes, and the occurrence of premature menopause.

The objectives of this project are to:

  • Determine whether existing and novel surrogate measures of infertility potential differ between female pediatric cancer patients and healthy controls.
  • Determine whether a relationship exists between surrogate measures of fertility potential and the dose of alkylating agents received by female pediatric cancer survivors.
  • Assess changes in existing and novel surrogate measures of fertility potential during and after chemotherapy in pediatric cancer patients.

Key Experiments

  • After recruiting and interviewing a prospective cohort of pediatric cancer survivors and age-matched healthy controls, a comparison of ovarian function as a whole and based on dose of alkylating agent will be conducted.  Various markers of ovarian function will be measured in order to establish their prognostic value for predicting impaired fertility and improving counseling methods on fertility preserving techniques
  • In pediatric patients, evaluate endocrine changes in the hypothalamic-pituitary-gonadal axis before and after chemotherapy with alkylating agents using various markers of ovarian function

Consortium Support and Impact

In order to recruit the appropriate number of patients for these studies and to take advantage of oncofertility mentorship, there must be close collaboration with the National Physicians Cooperative.  No study to date has conducted such a comprehensive evaluation of fertility potential in pediatric and young adult cancer survivors; therefore, this project provides an opportunity for close collaboration with social science researchers to determine the biosocial perspective of these patients.  The impact of pediatric cancer treatments on fertility potential will be directly informative to those studying the impact of treatments in the adult female and vice versaEducation of patients and physicians and training of oncofertility specialists will also be necessary to ensure an understanding of the impact of infertility in pediatric patients and that appropriate technology is translated into bedside care.

Publications

Gracia, C R. Reproductive Health After Cancer. Cancer and Treatment Research. 2010; 156: 3-9. PMID: 20811821.

Su HI, Sammel MD, Green J, Velders L, Stankiewicz C, Matro J, Freeman EW, Gracia CR, Demichele A. Antimullerian hormone and inhibin B are hormone measures of ovarian function in late reproductive-aged breast cancer survivors. Cancer. 2009 Nov 13.

 

This research was supported by the Oncofertility Consortium®, funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant UL1DE19587 and KL1CA133839.