Endocrine Female Infertility, Infertility, Female, Menopause Ovarian Failure, Menopause, Premature, Ovarian Failure, Ovarian Insufficiency
Conditions
Keywords
Primary ovarian insufficiency, Ovarian tissue transplantation, Immunosuppression, Premature menopause, Ovarian failure, Ovary transplant
Brief summary
Premature ovarian failure, also known as primary ovarian insufficiency (POI), or premature menopause, affects 1-2% of women under 40. The diagnosis is typically made based on high levels of follicle stimulating hormone (FSH) and absent or irregular menstrual periods. It leads to infertility and menopause-like effects (hot flashes and thin bones) due to low estrogen levels. POI can result from various factors such as genetic conditions, autoimmune diseases, or previous medical treatments like chemotherapy. Treatment of POI usually involves hormone replacement therapy and, if pregnancy is desired, assisted reproductive technologies such as in vitro fertilization (IVF) using an egg donor. However, IVF may not be an option for everyone due to personal, religious, ethical or financial reasons. Recent advances in medicine have identified ovarian tissue transplantation (OTT) as a potential solution. OTT involves transplanting either fresh or frozen ovarian tissue into the pelvic area, where it can begin functioning again. Studies in animals and humans have shown success in restoring hormonal function and even achieving pregnancies in some cases. Initial human trials of ovarian tissue transplants from another individual began with identical twins and have since expanded to include non-identical siblings with compatible tissue matches using immunosuppression. Success rates of OTT have been promising, with multiple live births reported between identical twins. Long-term studies indicate that transplanted tissue can remain functional for up to eight years. Ovarian tissue transplantation offers a promising avenue for women with POI to help restore fertility and hormonal function. Continued research and refinement of tissue techniques are essential to improve outcomes and expand access to this innovative treatment option. This study will enroll 10 participants who will undergo ovarian tissue transplantation donated by a non-identical sister using an immunosuppression protocol at University Hospitals.
Interventions
PROCEDUREOvarian tissue allo-transplantation
Participants will receive donor ovarian tissue with immunosuppression
Sponsors
University Hospitals Cleveland Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
(Donor): * Must meet criteria for ovarian sufficiency: Menstruating; Premenopausal serum hormone (FSH, LH, estradiol, AMH) levels * Must be between the ages of 21-35 years old. * Must be genetic sister to recipient participant, which will be assessed by patient report. * Must have history of at least one healthy live birth. * Must have more than one ovary (i.e. must have both the left and right ovary). * Must be willing to undergo a donor transplant evaluation including serologies and nucleic acid testing (NAT, which is essentially rapid PCR) for infectious conditions. * Must have normal female karyotype (46,XX). * Must have negative testing for HIV type 1 and 2, Hepatitis B, Hepatitis C, syphilis, West Nile Virus, gonorrhea and chlamydia. * Must be willing to undergo general anesthesia, minimally invasive gynecologic surgery, and loss of unilateral ovary. * If patient is a smoker, 3 months cessation is required prior to enrollment and must pass a nicotine test. * Must be willing and able to sign informed consent and follow all outlined procedures and recommendations in the protocol. * Donors (with their marital partners, when applicable) must be willing to seek independent legal advice from attorneys with specific expertise in third-party reproduction to determine their legal rights and duties in entering into a donor reproductive tissue arrangements. Inclusion Criteria (Recipient): * Must meet criteria for primary ovarian insufficiency: Amenorrheic x12 months; Serum hormone (FSH, LH, estradiol, AMH) levels consistent with menopause * Must be between the ages of 21-40 years old. * Must be in a committed relationship with a male partner. * Must be willing to attempt natural conception within 4 months following transplant. * Must be willing to undergo a pre-transplant evaluation. * Must be willing to undergo Maternal Fetal Medicine consultation and evaluation for safety of pregnancy, particularly patients at risk of complications in pregnancy (e.g. Turner syndrome patients). * Must be willing to undergo general anesthesia, minimally invasive gynecologic surgery, pregnancy with potential high risk complications, and surgery to remove the graft * Must be willing and able to receive potent immunosuppressive medications and must be able to follow standard infection prophylaxis protocols * Must have been offered and declined donor oocyte IVF as a first line treatment option * Must be willing to receive standard vaccinations such as influenza, Hepatitis B. If age and circumstances indicate, be willing to receive vaccines against pneumococcus, HPV and Hepatitis A. * If patient is a smoker, 3 months cessation is required prior to enrollment and must pass a nicotine test. * Must be willing and able to sign informed consent and follow all outlined procedures and recommendations in the protocol, including assent for monitoring neonatal outcomes for the first year after birth. * Intended parents (meaning, the recipient and partner) must be willing to seek independent legal advice from attorneys with specific expertise in third-party reproduction to determine their legal rights and duties in entering into a donor reproductive tissue arrangements. Inclusion Criteria (Recipient Male Partner) * Must be age 18 years or older (and a combined age not greater than 110 years). * Must have a normal semen analysis. * Must be willing and able to sign informed consent. * Intended parents (meaning, the recipient and partner) must be willing to seek independent legal advice from attorneys with specific expertise in third-party reproduction to determine their legal rights and duties in entering into a donor reproductive tissue arrangements.
Exclusion criteria
(Donor) (to be verified by history and review of the medical chart by the study team) * History of hypertension, diabetes, or significant heart, liver, kidney or central nervous system disease. * Any medical diagnosis placing the subject at high risk of surgical complications based on the team's review of medical history. * Current smoker (smoking cessation must have occurred 3 months prior to enrollment). * History of prior malignancy except for cervical cancer in stage 1a or 1b after 3 years. * History of human immunodeficiency virus (HIV), mycobacteria, hepatitis C. * Hepatitis B infection (Hepatitis B risk is for those with HepB surface antigen and/or HBV DNA positive. Those that are HepB core antibody true-positive are at minimal risk of reactivation. Those with vaccine-induced HepB surface antibody are not at risk). * Presence of active documented systemic infection or recent systemic infection within the past three months: Positive for syphilis (T. pallidum), chlamydia (C. trachomatis) or gonorrhea (N. gonorrhea). * BMI greater than 35 kg/m2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time (days) from transplantation to resumption of menses as measured by patient report | Up to 6 months |
| Number of live births as measured by medical record report/patient report | Up to 3 years |
Secondary
| Measure | Time frame |
|---|---|
| Time (days) from transplantation to pregnancy as measured by medical record/patient report | Up to 2 years |
Countries
United States
Contacts
CONTACTMegan Tribout, RN
PRINCIPAL_INVESTIGATORRebecca Flyckt, MD
University Hospitals Cleveland Medical Center
PRINCIPAL_INVESTIGATORKathryn Coyne, MD
University Hospitals Cleveland Medical Center
Outcome results
None listed