Ovarian Tissue Transplantation for Premature Ovarian Failure

Overseen By Kylie Phillips

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Rebecca Flyckt

Must be taking: Immunosuppressive medications

Disqualifiers: Hypertension, Diabetes, Heart disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be willing to take immunosuppressive medications and follow infection prevention protocols.

Is ovarian tissue transplantation safe for humans?

Ovarian tissue transplantation generally has a low risk of complications, similar to standard laparoscopy (a type of minimally invasive surgery). In a study of 1373 procedures, only three surgical complications were reported, and many women resumed menstruation and hormonal activity after the procedure. ^{1 2 3 4 5}

How is ovarian tissue allo-transplantation different from other treatments for premature ovarian failure?

Ovarian tissue allo-transplantation is unique because it involves transplanting ovarian tissue from a donor to restore ovarian function, potentially offering an alternative to oocyte (egg) donation. This approach may use immunomodulators like preimplantation factor (PIF) to help the body accept the transplanted tissue without the need for extensive immune suppression. ^{1 2 6 7 8}

What data supports the effectiveness of the treatment Ovarian Tissue Allo-transplantation for Premature Ovarian Failure?

Research shows that ovarian tissue transplantation has led to successful restoration of ovarian function and even live births in some cases, such as the first live birth in China after this procedure. Additionally, studies in animals like olive baboons have shown that allogeneic ovarian transplantation can restore ovarian function, suggesting potential effectiveness in humans. ^{1 2 3 9 10}

Who Is on the Research Team?

Kathryn Coyne, MD

Principal Investigator

University Hospitals Cleveland Medical Center

Rebecca Flyckt, MD

Principal Investigator

University Hospitals Cleveland Medical Center

Are You a Good Fit for This Trial?

This trial is for women under 40 with premature ovarian failure, leading to infertility and menopause-like symptoms. Participants should have high FSH levels and irregular periods. They must have a non-identical sister willing to donate ovarian tissue and agree to use immunosuppression.

Inclusion Criteria

I am willing to try for a natural pregnancy within 4 months after my transplant.

I am willing to undergo surgery and anesthesia, including for high-risk pregnancy.

If patient is a smoker, 3 months cessation is required prior to enrollment and must pass a nicotine test

Exclusion Criteria

I have a history of high blood pressure, diabetes, or major organ disease. My creatinine level is above 1.0 mg/dL.

I have a history of HIV, mycobacteria, or hepatitis C.

Any medical diagnosis placing the subject at high risk of surgical complications based on the team's review of medical history

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants undergo ovarian tissue transplantation donated by a non-identical sister using an immunosuppression protocol

1 week

1 visit (in-person)

Immunosuppression

Participants receive immunosuppression treatment to prevent rejection of the transplanted tissue

6 months

Follow-up

Participants are monitored for safety and effectiveness after transplantation

12 months

Quarterly visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Ovarian Tissue Allo-transplantation

Trial Overview The study tests ovarian tissue transplantation in women with premature ovarian insufficiency. It involves transplanting tissue from a compatible sister into the patient's pelvic area, aiming to restore hormonal function and fertility.

How Is the Trial Designed?

Group I: Ovarian tissue recipient Experimental Treatment 1 Intervention

Any recipient that receives ovarian tissue transplantation

Who Is Running the Clinical Trial?

Rebecca Flyckt

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

Laparoscopic removal and transplantation of ovarian tissue for fertility preservation in cancer patients have a very low complication rate, with only three complications reported out of 1373 procedures (0.2%).

After transplantation, 81% of women resumed menstruation, and 16 pregnancies were achieved in 14 patients, indicating that this method is effective for restoring fertility post-cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue. Beckmann, MW., Dittrich, R., Lotz, L., et al.[2018]

Ovarian tissue transplantation (OTT) has been performed successfully in 318 women across 21 countries, with 95% reporting renewed ovarian function and half of the children born after the procedure resulting from natural conception.

There is no evidence that OTT causes cancer recurrence, as malignancies diagnosed post-transplant were not linked to the procedure, suggesting it is a safe option for fertility preservation in women undergoing gonadotoxic treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort. Gellert, SE., Pors, SE., Kristensen, SG., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Reproductive outcome after transplantation of ovarian tissue: a systematic review. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Determinants of transplantation success with cryopreserved ovarian tissue: data from 196 women of the FertiPROTEKT network. [2022]

4. England pubmed.ncbi.nlm.nih.gov

First live birth in China after cryopreserved ovarian tissue transplantation to prevent premature ovarian insufficiency. [2022]

5. Czech Republic pubmed.ncbi.nlm.nih.gov

[Successful ovarian tissue transplantation in woman with premature ovarian failure after gonadotoxic treatment]. [2018]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue. [2018]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Transplantation of frozen-thawed ovarian tissue: an update on worldwide activity published in peer-reviewed papers and on the Danish cohort. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Influence of graft size, histocompatibility,and cryopreservation on reproductive outcome following ovary transplantation in mice. [2020]

9. Denmark pubmed.ncbi.nlm.nih.gov

Survival of ovarian allografts in an experimental animal model. [2007]

10. England pubmed.ncbi.nlm.nih.gov

Ovarian function and reproductive outcome after ovarian tissue transplantation: a systematic review. [2020]