Ovarian Tissue Allo-transplantation

Ovarian Tissue Allo-Transplantation in the Setting of Primary Ovarian Insufficiency Between Non-Genetically Identical Siblings With Use of Immunosuppression

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Menopause, Premature; Infertility, Female; Ovarian Failure; Ovarian Insufficiency; Menopause Ovarian Failure; Endocrine Female Infertility
• Intervention / Treatment: Procedure: Ovarian tissue allo-transplantation

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Megan Tribout, RN; Phone Number: 216-286-0763; Email: Megan.Tribout@UHhospitals.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
      • Contact: Kylie Phillips; Phone Number: 216-286-0765; Email: kylie.phillips@uhhospitals.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Exclusion Criteria (Recipient)

• History of hypertension, diabetes, or significant heart, liver, kidney or central nervous system disease. Serum creatinine level >1.0 mg/dL.
• 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).
• Active HPV infection.
• 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.
• Significant mental illness or substance abuse.
• BMI greater than 30 kg/m2
• Prior organ transplant with rejection, infection, or graft thrombosis.

Exclusion Criteria (Recipient Male Partner )

• Inability to complete regular intercourse.
• History of incarceration.
• Significant mental illness or substance abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ovarian tissue recipient; Any recipient that receives ovarian tissue transplantation	Procedure: Ovarian tissue allo-transplantation; Participants will receive donor ovarian tissue with immunosuppression

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Time (days) from transplantation to pregnancy as measured by medical record/patient report	Up to 2 years

Collaborators and Investigators

• Sponsor: Rebecca Flyckt
• Investigators: Principal Investigator: Rebecca Flyckt, MD, University Hospitals Cleveland Medical Center; Principal Investigator: Kathryn Coyne, MD, University Hospitals Cleveland Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): May 30, 2030
• Study Completion (Estimated): May 30, 2030

Study Registration Dates

• First Submitted: November 1, 2024
• First Submitted That Met QC Criteria: November 1, 2024
• First Posted (Actual): November 4, 2024

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunosuppression; Ovarian tissue transplantation; Premature menopause; Primary ovarian insufficiency; Ovarian failure; Ovary transplant
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genital Diseases, Female; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Infertility; Infertility, Female; Menopause, Premature; Primary Ovarian Insufficiency
• Other Study ID Numbers: STUDY20241094

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No