Clinical trial NCT02395341: The Longitudinal Ovarian Reserve Study
Official title: The Effects of Cancer Treatment on Ovarian Function: A Longitudinal Study by the Oncofertility Consortium
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Effects of Chemotherapy
Keywords: reproductive hormones
cancer survivors
endocrine function
antral follicle counts
female infertility due to diminished ovarian reserve
perimenopause
premature menopause
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Philadelphia
First posted: 2015-03-23
Enrollment: 20
Sex: FEMALE
Minimum age (years): 15
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be referred for this study by their primary oncologists. Eligible reproductive-aged girls and women newly diagnosed with cancer or another condition requiring chemotherapeutic intervention will be enrolled

Brief summary: Postmenarchal female cancer patients scheduled to undergo cancer therapy may enroll in this study to assess changes in existing and novel surrogate measures of fertility potential before, during and after chemotherapy. Measures of fertility potential to be tested include ultrasound imaging for antral follicle counts and ovarian volumes, endocrine evaluation, and assessment of oxidative stress.

Detailed description: Eligible women are asked to complete a structured interview, questionnaires, a monthly menstrual diary, a brief physical examination, a blood test, and an abdominal or pelvic ultrasound at baseline and at 3 month intervals following start of chemotherapy through 6 months post end of treatment.

Within subject changes in continuous variables (hormones, urinary isoprostane levels, ovarian volume, AFC) will be compared using paired t-tests (nonparametric tests as appropriate). Non-Gaussian-distributed variables will be logarithmically transformed prior to analysis. In general, changes from baseline to every 3 month assessment will be compared individually as well as changes from baseline to post treatment. In addition, regression models for repeated measures will be used to describe the pattern of change in these outcomes over time. Additional models will be constructed to adjust for potential confounding variables including age, chemotherapy type, dose and duration of treatment, radiation treatment, gonadotropin releasing hormone agonist use, and hormone use. Finally, regression models will be used to evaluate the association between changes in urinary isoprostane levels over the study with changes in endocrine measures.

Eligibility criteria: Inclusion Criteria:

* Females with the diagnosis of cancer schedules to be treated with chemotherapy and or radiation therapy.
* Age between 15-45 years.
* Post-menarchal.
* Presence of a uterus and both ovaries.
* Ability and willingness to comply with study protocol.
* Have given written informed concent (or assent with parental consent in minors), prior to any study-related procedure, not part of normal medical care, with the understanding that consent may be withdrawn byt he patient at any time without prejudice to their future medical care.

Exclusion Criteria:

* Current pregnancy.
* Lactation within the previous 3 months.
* Any medical condition other than cancer, with in the judgment of the investigator is known to be associated with premature ovarian failure (such as Turner's Syndrome or Fragile X) or ovulatory dysfunction (such as thyroid disease, adrenal dysfunction, Cushing's syndrome, hyperprolactinemia, and polycystic ovarian syndrome).

Primary outcomes:
measure: Change from baseline in reproductive hormone measures, during and after chemotherapy.
timeFrame: 18-24 months: pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
Secondary outcomes:
measure: Change from baseline in ovarian volume during and after chemotherapy.
timeFrame: 18-24 months: Pelvic ultrasound will be performed at Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
measure: Change from baseline in antral follicle counts during and after chemotherapy.
timeFrame: 18-24 months: Pelvic ultrasound will be performed at Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
measure: Change in urinary isoprostane levels from baseline to 6 months after end of chemotherapy
timeFrame: 18-24 months: 24 hour urine collection will be performed at Pre-chemotherapy baseline and at the final study visit.
measure: Change from baseline in menstrual characteristics
timeFrame: 18-24 months: Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
measure: Change from baseline in menopausal symptoms
timeFrame: 18-24 months: Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
measure: Change from baseline in quality of life measures
timeFrame: 18-24 months: Pre-chemotherapy baseline and at 3 month intervals from start of chemotherapy through 6 months after end of chemotherapy.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Penn Reproductive Research Unit, 3701 Market Street, Suite 810
state: Pennsylvania
city: Radnor
country: United States
facility: Penn Medicine at Radnor, 250 King of Prussia Road
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Clarisa R Gracia, MD, MSCE
role: PRINCIPAL_INVESTIGATOR
References: