Assessing Fertility Potential in Female Cancer Survivors

Study Overview
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Brief Summary
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Hypothesis: Girls and women exposed to chemotherapy and/or radiation therapy experience endocrine changes more similar to women in their late reproductive years than to same-age peers. These changes will be more dramatic in women who receive high dose therapy compared to women who receive low dose therapy. At annual visits over 3-5 years, a combination of physical exam, medical history, menstrual diary keeping, pelvic ultrasound and blood hormones tests will be used to measure ovarian reserve , that is the number and quality of the eggs that remain in the ovaries. The study will also try to learn if those who received higher doses of certain chemotherapies are more likely to have changes in these tests sooner than those women who received smaller doses of these same drugs. Additionally a DNA (deoxyribonucleic acid) sample will be collected to look for gene variations that may predict susceptibility to ovarian damage from cancer treatments. Information learned from this study may help researchers to develop guidelines to identify problems with a female cancer survivor's ovaries before irregular menses or other symptoms of ovarian failure occur.

Detailed Description
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Up to 400 females will participate in this study in one of three cohorts: 150 females ages 11-35, with history of exposure to alkylating agent chemotherapy and/or radiation therapy 150 Unexposed peers, ages 11-35, never exposed to chemotherapy or radiation therapy 100 Unexposed females, ages 40-50 never exposed to chemotherapy or radiation therapy

Official Title
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Assessing Fertility Potential in Female Cancer Survivors

Conditions
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Effects of Chemotherapy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for cancer survivors: Previous treatment with chemotherapy and/or radiation therapy for either cancer or another illness. Age between 11-35 years. Post-menarchal. Presence of a uterus and at least one ovary. Ability and willingness to comply with study protocol. Have given written informed consent, prior to any study-related procedure, not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. Inclusion Criteria for controls: Healthy females who have never been treated for cancer. Age between 11-35 and 40-50 years. Post-menarchal with regular cyclic menses (every 21-35 days) Presence of a uterus and at least 1 ovary. Ability and willingness to comply with study protocol. Have given written informed concent, prior to any study-related procedure, not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. Exclusion Criteria: Current pregnancy. Use of hormonal contraception or use of hormone replacement therapy within the previous 4 weeks. Lactation within the previous 3 months. Chronic illness that would limit ability of participant to comply with study protocol. Any known medical condition, other than cancer, which in the judgement 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). For controls, a history of infertility.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposed females, ages 11-40<br>Prior exposure to alkylating agent chemotherapy and/or radiation therapy At least 1 year from completion of chemotherapy and/or radiation therapy Uterus and at least one ovary are present Not pregnant or breastfeeding in the past 3 months Not taking any hormones or oral contraceptives for at least 4 weeks prior to study visits No medical condition (other than cancer) known to be associated with premature ovarian failure (such as Turner's Syndrome or Fragile X) or ovulatory dysfunction (such as thyroid disease, congenital adrenal hyperplasia, Cushing's syndrome, hyperprolactinemia, and polycystic ovary syndrome). | |
| Unexposed females, ages 40-50<br>Never exposed to chemotherapy or radiation therapy Regular menstrual cycle (every 21-35 days) Uterus and at least one ovary are present Not pregnant or breastfeeding in the past 3 months Not taking any hormones or oral contraceptives for at least 4 weeks prior to study visits No medical condition known to be associated with premature ovarian failure (such as Turner's Syndrome or Fragile X) or ovulatory dysfunction (such as thyroid disease, congenital adrenal hyperplasia, Cushing's syndrome, hyperprolactinemia, and polycystic ovary syndrome). | |
| Unexposed females, ages 11-35<br>Never exposed to chemotherapy or radiation therapy Regular menstrual cycle (every 21-35 days) Uterus and at least one ovary are present Not pregnant or breastfeeding in the past 3 months Not taking any hormones or oral contraceptives for at least 4 weeks prior to study visits No medical condition known to be associated with premature ovarian failure (such as Turner's Syndrome or Fragile X) or ovulatory dysfunction (such as thyroid disease, congenital adrenal hyperplasia, Cushing's syndrome, hyperprolactinemia, and polycystic ovary syndrome). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reproductive hormones | Primary Outcomes for this study will include mean and changes in reproductive hormone measures obtained during the early follicular phase of the menstrual cycle (days 1-4). | Annually for 3-5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antral Follicle Counts | All ovarian follicles and cysts will be measured by transvaginal or transabdominal ultrasound. Follicles will be measured in millimeters and grouped according to size: 2-5 mm, 6-9 mm, and >10 mm in diameter. | Annually for 3-5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oncofertility, Fertility, Late effects, cancer, chemotherapy, radiation therapy, survivor, ovarian reserve, premature ovarian failure, early menopause, healthy volunteers, perimenopause, middle age, pediatric survivors, healthy women