Assessing Fertility Potential in Female Cancer Survivors

April 12, 2021 updated by: University of Pennsylvania

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.

Study Overview

Status

Completed

Conditions

Effects of Chemotherapy

Detailed Description

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

Study Type

Observational

Enrollment (Actual)

391

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

United States
- Pennsylvania
  - Philadelphia, Pennsylvania, United States, 19104
    - Penn Reproductive Research Unit, 3701 Market Street, Suite 810
  - Radnor, Pennsylvania, United States, 19087
    - Penn Medicine at Radnor, 250 King of Prussia Road

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years to 50 years (ADULT, CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Subjects with a history of cancer, or other conditions treated by chemotherapy, will be identified through local survivorship programs or self-referral. In addition, two groups of regularly menstruating unexposed subjects will be recruited through local advertising: a group of similar-age subjects and another group in the late reproductive years. Exposed and unexposed controls will be frequency matched with respect to age (within 2 years) at enrollment. In addition,subjects will be balanced with respect to self reported race/ethnicity. Enrollment is purposefully targeted and stratified for this study to reflect the population in the pediatric and adult oncology practices.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Exposed females, ages 11-40 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 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 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?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reproductive hormones Time Frame: Annually for 3-5 years	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 Time Frame: Annually for 3-5 years	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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

Children's Hospital of Philadelphia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Gracia CR, Sammel MD, Freeman E, Prewitt M, Carlson C, Ray A, Vance A, Ginsberg JP. Impact of cancer therapies on ovarian reserve. Fertil Steril. 2012 Jan;97(1):134-40.e1. doi: 10.1016/j.fertnstert.2011.10.040. Epub 2011 Dec 2.

Helpful Links

Select "Clinical Trials" for Current Studies at Penn's Women's Health Clinical Research Center.For more information about participating in one of Penn Fertility Care's research studies please call 1-800-789-PENN.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 1, 2006

Primary Completion (ACTUAL)

March 30, 2020

Study Completion (ACTUAL)

March 30, 2020

Study Registration Dates

First Submitted

June 11, 2010

First Submitted That Met QC Criteria