Immune System Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Autoimmune Diseases

Infertility

Infertility, Male

Genital Diseases

Urogenital Diseases

Genital Diseases, Male

Male Urogenital Diseases

Stem cell transplantation Testicular tissue grafting

Spermatogonial stem cell transplant and testicular tissue grafting is performed to produce sperm.

Spermatogonial Stem Cell Transplant and Testicular Tissue Grafting

Rachel Neelley

Kyle E Orwig, PhD

Spermatogonial stem cell transplantation through ultrasound guided rete testis injection and testicular tissue grafting will be performed for participants who have frozen testicular tissue prior to gonadotoxic therapy. The purpose of this study is to test the safety and feasibility of these transplant technologies and restore fertility for these participants.

Azoospermia (no sperm in ejaculated semen) impacts 1% of men in the general population and 15% of infertile men, which translates to 645,000 males between the ages of 20 and 50 (prime reproductive years) in the United States. Spermatogenesis arises from a population of spermatogonial stem cells in the testes that maintain continuous sperm production throughout a man's post-pubertal life. Diseases or medical treatments that compromise the stem cell pool and/or prevent the stem cells from differentiating can cause infertility. Adult men have the option to cryopreserve a semen sample prior to therapy but this is not an option for prepubertal patients who are not yet producing sperm. This study will test the safety and feasibility of two approaches to restore sperm production using previously cryopreserved testicular tissues, which contain spermatogonial stem cells.

The first approach is autologous transplantation of testicular cells, including spermatogonial stem cells, into the testis using ultrasound-guided rete testis injection. The second approach is autologous grafting of intact pieces of testicular tissue under the skin in the scrotum.

Spermatogonial Stem Cell (SSC) Transplant and Testicular Tissue Grafting

The investigators will publish individual participant data, after deidentification. The investigators will also report each individual participants data back to them. Participants will be identified with unique ID numbers. No identifiable information will be shared.

Rate of participants where sperm was found in semen analysis or testicular tissue analysis

Rate of participants diagnosed with cancer recurrence

Rate of infection, hospital readmission, re-operation occurs

University of Pittsburgh

Professor

Gland and Hormone Related Diseases

Premature Birth

Primary Ovarian Insufficiency

Menopause, Premature

Menopause

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Reproductive Control Agents

Hormones

Epinephrine

Racepinephrine

Epinephryl borate

Contraceptive Agents

Contraceptives, Oral

Alkylating Agents

* 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).

* 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).

Clarisa R Gracia, MD, MSCE

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.

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

Assessing Fertility Potential in Female Cancer Survivors

Data will be shared with Dr. Jill Ginsberg, a co-investigator of the study.

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).

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.

Children's Hospital of Philadelphia

University of Pennsylvania

Testicular biopsy is performed to obtain testicular tissue for cryopreservation

Testicular biopsy

Kyle Orwig, PhD

Testicular tissue cryopreservation is an experimental procedure where a young boy's testicular tissue is retrieved and frozen. This technique is reserved for young male patients who are not yet producing mature sperm, with the ultimate goal that their tissue may be used in the future to restore fertility when experimental techniques emerge from the research pipeline.

Fertility status has an important impact on the post-treatment quality of life for cancer survivors and other patients that receive gonadotoxic therapies (e.g., prior to bone marrow transplantation). Semen cryopreservation is an established fertility preserving therapy, but is not accessible or appropriate for all men. Currently there are no therapies to preserve the future fertility of preadolescent boys. However, new reproductive therapies are under development and may one day offer "fertile hope" to those survivors that do not currently have access to fertility preserving therapies. Clinical management of fertility threatening diseases and treatments must have foresight of the gonadotoxic side effects and the potential for infertility. When no established fertility sparing options are available, it is reasonable to offer harvesting and cryopreservation of testicular tissue as a possible means of fertility preservation.

This study will harvest testicular tissue from eligible patients. Separate portions of the harvested tissue and/or cells will be 1) designated for research and 2) cryopreserved and maintained for participating patients as a resource for future elective procedures to attempt fertility restoration.

Testicular Tissue Cryopreservation for Fertility Preservation

Testicular Tissue Cryopreservation for Fertility Preservation in Patients Facing Infertility-causing Diseases or Treatment Regimens

The investigators will publish individual participant data. The investigators will also report each individual participants data back to them. Participants will be identified with unique ID numbers. No identifiable information will be shared.

A segment of testicular specimen (\~5%) will be removed and assessed for presence of spermatogonial stem cells by immunofluorescence and hematoxylin staining

Children's National Research Institute

Children's Hospital of Orange County

Children's Hospital Medical Center, Cincinnati

Ann & Robert H Lurie Children's Hospital of Chicago

Medical College of Wisconsin

Connecticut Children's Medical Center

Nationwide Children's Hospital

Washington University School of Medicine

Alfred I. duPont Hospital for Children

University of Miami

University of Chicago

Cook Children's Medical Center

Helen DeVos Children's Hospital

Seattle Children's Hospital

University of Texas

Oregon Health and Science University

Hackensack Meridian Health

Indiana University Health

Otherwise healthy, mid-reproductive aged women between the ages of 20 and 35 years previously exposed to high dose alkylating agent therapy (or have an alkylator score of 1 or more), and at least 1 year from cancer treatment.

Healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy.

Reproductive aged women between the ages of 43-50 who have not been exposed to cancer therapy, nor have a history of infertility

Women of late to mid reproductive age may participate in a study using novel methodology to identify subtle changes in the reproductive endocrine axis via daily urine hormone analysis, which may have important implications for reproduction and may signal reproductive senescence.

Women with a reduced follicular pool either from natural aging or previous chemotherapy, may not have any clinical signs or symptoms and traditional measures of ovarian reserve, such as basal Follicle Stimulating Hormone may be within the normal range. However, there may be alterations in the luteal or follicular phases(shortened follicular phase and luteal insufficiency) due to compromised follicle competency and alterations in the H-P-O axis. Therefore this aim uses novel methodology to identify subtle changes in the reproductive endocrine axis which may have important implications for reproduction and may signal reproductive senescence. Compared to yearly follicular measures of reproductive hormones, daily urine hormone analysis provides a more integrative assessment.

Three groups of subjects will be recruited:

Group 1: Otherwise healthy, mid-reproductive aged women between the ages of 20 and 35 years previously exposed to high dose alkylating agent therapy (or have an alkylator score of 1 or more), and at least 1 year from cancer treatment.

Group 2: healthy, mid-reproductive aged women between the ages of 20 to 35 who have not been exposed to cancer therapy.

Group 3: healthy, late reproductive aged women between the ages of 43-50 who have not been exposed to cancer therapy, nor have a history of infertility.

Subjects in all groups must have regular menstrual cycles every 21-35 days, and have a uterus and both ovaries. Each participant will complete daily urinary collections for 2 menstrual cycles to assess reproductive hormones. The ultimate goal of this work is to better estimate the reproductive window, or time to menopause.

daily urinary collections for 2 menstrual cycles

Assessing Urinary Hormones in Female Cancer Survivors

Follicular and Luteal Dysfunction in Cancer Survivors

Integrated urinary follicular-phase Follicle Stimulating Hormone (FSH) in urine samples collected daily for 2 menstrual cycles will be measured in mIU/mL by means of two-site chemiluminescent immunoassay with the use of two monoclonal antibodies.

Integrated urinary follicular-phase Luteinizing Hormone (LH) in urine samples collected daily for 2 menstrual cycles will be measured in mIU/mL by means of two-site chemiluminescent immunoassay with the use of two monoclonal antibodies.

Estrone Conjugate (E1C) in urine samples collected daily for 2 menstrual cycles will be measured in ug/dL by means of E1C immunoassay.

Pregnanediol-glucuronide (PDG) in urine samples collected daily for 2 menstrual cycles will be measured in ug/mL by means of PDG immunoassay.

Urinary Creatinine in urine samples collected daily for 2 menstrual cycles will be measured in mg/mL by means of spectrophotometric assay.

Participants will be provided with calendars on which to record detailed menstrual cycle information during the study. The total menstrual cycle length will be defined as the number of days from day 1 of menses to the day before the next menses. The Kassam method will be used to determine evidence of luteal activity, presumably ovulation. Follicular phase will be defined as the number of days from day 1 of menses up to the day of luteal transition and the luteal phase length will be defined as the number of days beginning from the day after the day of luteal transition to the day before the next menses.

Neoplasms

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Nurses in the control group accepted the other non-fertility (standard) nursing training for the intervention, whereas those in the experimental group accepted the oncofertility training. Based on research ethics and design, a standard education course was held for the control group after completing data collection in the nursing experimental group. We began to recruit patients into the patient experimental group after all nurses completed their educational courses.

We designed the education program according to Klein's NDM model, which explored the reasoning mechanism behind decision-making (Klein, 1993). It depends on the on-the-job training date in each unit. The education program consisted of the following: (1) Information accumulation: explanations of common cancer therapies related to subsequent infertility, psychological and mental change in cancer survivors with infertility, the necessity and method of early determination of fertility intention, and type of fertility preservation. (2) Sense-making: situational case sharing, emphasis on the guidance interaction between experienced and novice nurses to understand the patient's situation. (3) Decision-making: how to provide support, how to correspond, and attitudes toward people with strong fertility intention.

Naturalistic Decision-Making Model-based Oncofertility Care Education

Sheng-Miauh Huang, PhD

his study examined the effects of an oncofertility education program on decisional conflict in nurses caring for breast cancer patients and patients with breast cancer. Other predictors of decisional conflict were also examined.

Background: Nurses play an essential role in transferring knowledge to patients. However, several factors cause nurses to adopt a negative attitude toward providing oncofertility care.

Objective: This study examined the effects of an oncofertility education program on decisional conflict in nurses caring for breast cancer patients and patients with breast cancer. Other predictors of decisional conflict were also examined.

Design: Randomized, controlled experimental research. Settings and Participants: Patients (61) with breast cancer and nurses (79) were recruited from a hospital in Taipei, Taiwan.

Methods: The nursing participants were randomly assigned to receive oncofertility education (experimental group) or usual education (control group). Data from female patients in the control and experimental groups were collected before and after the nurses' educational training, respectively. The oncofertility education consisted of one face-to-face educational session and reading one educational booklet based on the Naturalistic Decision-Making (NDM) Model. The decisional conﬂict was measured using the Chinese version of the decisional conﬂict scale.

This study examined the effects of an oncofertility education program on decisional conflict in nurses caring for breast cancer patients and patients with breast cancer.

Effects of Naturalistic Decision-Making Model-based Oncofertility Care Education

Effects of Naturalistic Decision-Making Model-based Oncofertility Care Education for Nurses and Patients With Breast Cancer

The decisional conﬂict was measured using the Chinese version of the decisional conﬂict scale. Each item was rated on a five-point Likert scale, ranging from zero to 4. The score was calculated by averaging the sum of individual item scores, then multiplying the product by 25. Hence, the scores range from 0 to 100. A higher score indicates higher decisional conﬂict. Both nursing and patient participants were asked to fill out the questionnaire.

An Oncofertility Barrier Scale was developed to assess nurses' perceptions of comprehensive barriers regarding oncofertility care. The responses to each item were provided using a five-point Likert scale. A higher scale score meant the nurses perceived that it was more difficult to provide oncofertility care.

We used the Infertility Knowledge Questionnaire to measure both of nurses' and patients' knowledge of infertility in patients with breast cancer. Total scores for the 11 items ranged from zero to 11. Centimeters were used to show the ratio of correct answers visually. A higher score meant a greater level of knowledge about infertility. Both nursing and patient participants were asked to fill out the questionnaire.

The Fertility Intention Scale with 15 items was used to measure patients' fertility intentions. The standardized scale ranged from 1 to 5 points on a five-point Likert scale. Higher scores indicated a greater degree of fertility intention.

Mackay Medical College

the Office of Research and Development

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Gonadal Disorders

Endocrine System Diseases

Females ages 11-35 to be exposed to alkylating agent chemotherapy

Women of reproductive age who will receive treatment for cancer that includes chemotherapy may participate in a study measuring ovarian function over time. Eligible women are asked to complete a questionnaire, a menstrual diary, a brief physical examination, an ultrasound, and a blood test before, during and after cancer treatment.

A total of 7 study visits will be completed at 3 month intervals including 1 visit prior to treatment, and at least 2 visits after completion of treatment. Duration of study participation is 18-30 months, depending on length of treatment.

Review and Documentation of Cancer Therapy will be abstracted from the clinical oncology chart by the oncology offices caring for the patient. Treatment will be summarized in terms of chemotherapeutic type, duration and cumulative dose; total radiation dose and location; history and type of bone marrow transplantation; and any surgery. Any attempts at fertility preservation or use of gonadotropin releasing hormone agonist treatment during cancer therapy will be captured as well.

Ovarian Reserve After Cancer: Longitudinal Effects

Ovarian Reserve After Cancer: Longitudinal Effects A Multicenter Prospective Cohort Study by the Oncofertility Consortium

Subjects are asked to document menstrual bleeding in a diary, noting duration of each menstrual period in days, bleeding intensity (spotting, light, moderate, heavy, flooding, none), and intervals between periods.

The validated "Menopausal Symptom List" (MSL) will be used at each study visit to assess the presence or absence of menopausal symptoms during the past month, the frequency and severity of each symptom. Symptoms captured include: hot flashes, vaginal dryness, concentration/memory problems, irritability, mood swings, feeling sad, feeling anxious, trouble sleeping, aches, joint pain, headaches.

Ovaries will be measured in three dimensions. Uterine size and endometrial thickness will also be performed. The transvaginal approach is preferred, but transabdominal ultrasound will be performed in girls who do not feel comfortable with the transvaginal procedure.

20 mls blood will be obtained at stated timepoints for determining levels of Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Inhibin B, and Anti-mullerian Hormone (AMH). In menstruating girls and young women hormone measures will be obtained during the early follicular phase of the menstrual cycle (days 1-4). In women with irregular cycles the testing will be done spontaneously without regard for the bleeding pattern.

After the intervention implementation, all breast cancer patients presenting to oncology clinical visits that meet eligibility criteria will receive the multi-component oncofertility care intervention.

Prior to the intervention implementation, all breast cancer patients presenting to oncology clinical visits that meet eligibility criteria will receive usual care.

The intervention includes:

1. Young breast cancer patients presenting to oncology visits will complete a clinic-based oncofertility needs screen with a member of the clinical team. This needs screen assesses i) desire to have a child in the future, ii) need for contraception, and iii) sexual health/menopause symptoms.
2. A women's health survivorship care plan (SCP) in Spanish and English encompasses content on screening and management strategies for a) fertility concerns/pregnancy health; b) contraception; c) hot flashes and d) sexual health.
3. Oncofertility navigation consists of one telehealth or in-person session with a social worker to: i) assess the patient's oncofertility needs, ii) review the women's health SCP, iii) provide support with the goal of engaging in oncofertility care.
4. Oncofertility consultation as indicated via telehealth or in person will occur between the patient and reproductive specialist. Each consultation is estimated to be 1 hour.

Multi-component oncofertility care intervention

Sally Romero, PhD, MPH

H. Irene Su, MD, MSCE

The purpose of this study is to evaluate the effectiveness of a multi-component intervention to improve young breast cancer survivors' engagement in goal-concordant oncofertility care, concurrently with observing and gathering information on how the intervention is implemented. The investigators hypothesize that implementation of the intervention will result in increased young breast cancer survivors' engagement in goal-concordant oncofertility care.

Intervening on Women's Health for Rural Young Breast Cancer Survivors

Deidentified individual participant data generated during the study will be available from the principal investigator (H. Irene Su) upon reasonable request.

Study staff will be trained to abstract the primary outcome of engagement in goal-concordant oncofertility care from the patient's medical records using standardized case report forms. Engagement in goal-concordant oncofertility care will be assigned to young breast cancer survivors who undergo: 1) oncofertility needs screen, complete a navigation session, receive the women's health survivorship care plan (SCP), and thereafter have no oncofertility needs; OR 2) oncofertility needs screen, complete a navigation session, receive the SCP, have an oncofertility need, undergo telehealth oncofertility consultation, and thereafter have no oncofertility services needs; OR 3) oncofertility needs screen, complete a navigation session, receive the SCP, have an oncofertility need, undergo telehealth oncofertility consultation, have an oncofertility services need, and thereafter uptake appropriate services.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Spermatogonial Stem Cell (SSC) Transplant and Testicular Tissue Grafting	NCT04452305	Infertility, Ma... Cancer Autoimmune Diso...	Spermatogonial ...	-	University of Pittsburgh
Assessing Fertility Potential in Female Cancer Survivors	NCT01143844	Effects of Chem...		11 Years - 50 Years	University of Pennsylvania
Testicular Tissue Cryopreservation for Fertility Preservation	NCT02972801	Cancer Autoimmune Diso...	Testicular biop...	-	University of Pittsburgh
Assessing Urinary Hormones in Female Cancer Survivors	NCT03197532	Effects of Chem...		20 Years - 50 Years	University of Pennsylvania
Assessing Fertility Potential in Female Cancer Survivors	NCT01143844	Effects of Chem...		11 Years - 50 Years	University of Pennsylvania
Spermatogonial Stem Cell (SSC) Transplant and Testicular Tissue Grafting	NCT04452305	Infertility, Ma... Cancer Autoimmune Diso...	Spermatogonial ...	-	University of Pittsburgh
Effects of Naturalistic Decision-Making Model-based Oncofertility Care Education	NCT04600869	Fertility Issue... Breast Cancer Education	Naturalistic De...	22 Years - 65 Years	Mackay Medical College
Effects of Naturalistic Decision-Making Model-based Oncofertility Care Education	NCT04600869	Fertility Issue... Breast Cancer Education	Naturalistic De...	22 Years - 65 Years	Mackay Medical College
Ovarian Reserve After Cancer: Longitudinal Effects	NCT02467231	Effects of Chem... Premature Ovari...		11 Years - 35 Years	University of Pennsylvania
Intervening on Women's Health for Rural Young Breast Cancer Survivors	NCT05414812	Breast Cancer Fertility Contraception Menopausal Symp...	Multi-component...	18 Years - 50 Years	University of California, San Diego
Testicular Tissue Cryopreservation for Fertility Preservation	NCT02972801	Cancer Autoimmune Diso...	Testicular biop...	-	University of Pittsburgh
Effects of Naturalistic Decision-Making Model-based Oncofertility Care Education	NCT04600869	Fertility Issue... Breast Cancer Education	Naturalistic De...	22 Years - 65 Years	Mackay Medical College

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