Autologous Ovarian Tissue Transplant for Infertility

Overseen By Rachel Neelley

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: University of Pittsburgh

Disqualifiers: High surgical risk, BRCA mutations, Leukemia, Ovarian cancer, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

5 Participants Needed

Trial Summary

What is the purpose of this trial?

Chemotherapy and radiation for cancer and other conditions can cause infertility. Several centers around the world are cryopreserving ovarian tissue from these patients though an experimental protocol, including the Fertility Preservation Program in Pittsburgh (protocol PRO08050491). The objective of this study is to study the efficacy and safety of autologous tissue transplantation in patients diagnosed with primary ovarian insufficiency after chemotherapy and/or radiation treatments.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is autologous ovarian tissue transplantation safe for humans?

Research shows that autologous ovarian tissue transplantation, which involves freezing and later transplanting ovarian tissue, is generally considered safe for humans. Studies have been conducted on women with various conditions, and the procedure has been used to restore fertility and delay menopause, with no major safety concerns reported. ^{1 2 3 4 5}

How is the treatment of autologous ovarian tissue transplant for infertility unique compared to other treatments?

Autologous ovarian tissue transplant is unique because it involves transplanting a woman's own previously frozen ovarian tissue back into her body, which can restore fertility after treatments like chemotherapy that may damage the ovaries. This method is particularly promising for preserving fertility in young girls and women who cannot delay cancer treatment, as it is the only option available for prepubertal girls. ^{5 6 7 8 9}

What data supports the effectiveness of the treatment Autologous Ovarian Tissue Transplant for Infertility?

Research shows that autologous ovarian tissue transplantation, where a woman's own ovarian tissue is frozen and later transplanted back, is a promising method for preserving fertility, especially in cancer patients. Studies indicate that this treatment can help restore fertility, although outcomes can vary depending on individual factors. ^{1 5 6 10 11}

Research Team

Kyle Orwig, PhD

Principal Investigator

University of Pittsburgh/University of Pittsburgh Medical Center

Eligibility Criteria

This trial is for women who have lost their fertility due to cancer treatments like chemotherapy or radiation and had previously frozen ovarian tissue. They must be in good health, cleared by an oncologist, and either have primary ovarian insufficiency or wish to become pregnant. Women at high surgical risk, with pregnancy contraindications, BRCA mutations, certain cancers, psychological issues preventing consent, or current pregnancy cannot join.

Inclusion Criteria

You are unable to have children or are planning to become pregnant.

Oncologist's clearance

I have my ovarian tissue frozen.

Exclusion Criteria

I have a history of leukemia, ovarian cancer, or a cancer that affected my ovaries.

I am at high risk for complications if I undergo surgery.

I am a woman who cannot become pregnant due to health reasons.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-operative

Eligible subjects complete infectious disease testing and quality of life survey before ovarian tissue thawing and transplantation

1 week

1 visit (in-person)

Transplantation

Ovarian tissue thawing and transplantation performed via laparoscopy or minilaparotomy

1 day

1 visit (in-person)

Post-operative Assessment

Assessment within six weeks post-transplant to ensure recovery and emotional well-being

6 weeks

1 visit (in-person)

Follow-up

Series of follow-up assessments to monitor reproductive hormone levels, menstrual function, and complications

24 months

5 visits (in-person)

Long-term Follow-up

Annual survey starting year 3 post-transplantation to collect data on menstrual/pregnancy history and other outcomes

Up to 15 years

Treatment Details

Interventions

• Ovarian tissue transplant

Trial Overview The study tests the effectiveness and safety of transplanting a woman's own previously frozen ovarian tissue back into her body. This procedure aims to restore fertility in women who became infertile after receiving cancer treatment.

Participant Groups

Group I: Ovarian tissue transplant Experimental Treatment 1 Intervention

Transplantation of ovarian tissue into the abdomen. Only for patients who have previously frozen ovarian tissue

Ovarian tissue transplant is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Autologous Ovarian Tissue Transplantation for:

• Primary ovarian insufficiency after chemotherapy and/or radiation treatments

Approved in United States as Autologous Ovarian Tissue Transplantation for:

• Primary ovarian insufficiency after chemotherapy and/or radiation treatments

Approved in Canada as Autologous Ovarian Tissue Transplantation for:

• Primary ovarian insufficiency after chemotherapy and/or radiation treatments

Who Is Running the Clinical Trial?

University of Pittsburgh

Lead Sponsor

Trials

1,820

Recruited

16,360,000+

Findings from Research

The study established an optimal osmotic balance duration for vitrifying ovarian cortex tissue, finding that durations of 7, 11, and 19 minutes yielded the best follicle and stromal cell morphology for different tissue sizes.

A new formula (T=(S+15)/5) was developed to calculate the ideal osmotic balance time based on the size of the ovarian cortex, which can enhance the success of fertility preservation techniques like auto-transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appropriate Osmotic Balance Duration for Different Volumes of Ovarian Tissue in Vitrification Solution: a Study of Ovary Tissue Vitrification and Transplantation in Sheep. Dang, L., Zheng, X., Chang, Q., et al.[2018]

Transplanting ovarian tissue into the kidney capsule of mice resulted in significantly higher follicle counts and better outcomes for in vitro maturation (IVM) of oocytes compared to transplants in muscle sites.

The study suggests that the kidney capsule is the most effective site for ovarian tissue auto grafting, enhancing both follicular survival and the ability to mature oocytes, which is crucial for fertility preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of ovarian tissues autografted to various body sites followed by IVM in mouse. Khalili, MA., Dehghan, M., Nazari, S., et al.[2021]

In a study of 11 women who underwent ovarian tissue transplantation followed by assisted reproductive technology, the overall pregnancy rate was low at 7.4% per embryo transfer, indicating poor reproductive outcomes for IVF in this context.

Women without infertility factors had a higher chance of natural conception, with five patients achieving nine pregnancies and four live births spontaneously, while those with infertility factors experienced significantly lower reproductive success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of assisted reproductive technology after ovarian tissue transplantation in a cohort of 11 patients with or without associated infertility factors. Vatel, M., Torre, A., Paillusson, B., et al.[2022]

Transplanted cryopreserved ovarian tissue can remain functional for up to 10 years, with a successful pregnancy rate of about 31% among women wishing to conceive, based on a study of 41 women who underwent 53 transplantations.

The procedure has shown a low relapse rate in cancer survivors, indicating that the transplantation is generally safe, although some relapses occurred that were unlikely linked to the transplanted tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark. Jensen, AK., Kristensen, SG., Macklon, KT., et al.[2022]

Autotransplantation of cryopreserved ovarian tissue is a promising method for fertility preservation, with 30 successful births reported and restoration of ovarian activity occurring within 3.5 to 6.5 months after transplantation.

This technique offers unique advantages, such as not delaying cancer treatment, being safer for hormone-dependent cancers, and being the only option available for prepubertal girls, while also restoring both fertility and hormonal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autotransplantation of cryopreserved ovarian tissue--effective method of fertility preservation in cancer patients. Gamzatova, Z., Komlichenko, E., Kostareva, A., et al.[2014]

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]

Ovarian tissue cryopreservation and autotransplantation have been recognized as effective methods for restoring ovarian function and fertility, transitioning from experimental to accepted fertility preservation procedures by the American Society of Reproductive Medicine.

The review discusses the potential benefits and risks of using ovarian cryopreservation in healthy women for fertility preservation and menopause delay, highlighting the need for careful assessment and further research to optimize this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delaying Reproductive Aging by Ovarian Tissue Cryopreservation and Transplantation: Is it Prime Time? Oktay, KH., Marin, L., Petrikovsky, B., et al.[2022]

In a study involving 11 patients with borderline ovarian tumors (BOTs), cryopreserved ovarian tissue transplantation was found to potentially reintroduce BOT cells, as they were detected in 1 out of 11 patients after xenografting.

The study highlights the importance of preimplantation analysis of cryopreserved ovarian tissue, as it cannot be guaranteed that all fragments are free of malignant cells, emphasizing the need for caution in such procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of ovarian tissue transplantation in patients with borderline ovarian tumors. Masciangelo, R., Bosisio, C., Donnez, J., et al.[2022]

The establishment of human ovarian tissue banks is growing, but there is a lack of clear strategies for effectively utilizing cryopreserved ovarian tissue, particularly in cancer patients.

The paper suggests that cryopreserving an intact ovary with its vascular pedicle could be a promising alternative to current methods, highlighting the need for further research into both cryopreservation techniques and surgical methods for autotransplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian tissue banking for cancer patients: reduction of post-transplantation ischaemic injury: intact ovary freezing and transplantation. Bedaiwy, MA., Falcone, T.[2022]

Ovarian tissue preservation and transplantation can help women undergoing aggressive cancer treatments, with the first successful live birth from this procedure occurring in 2002, highlighting its potential efficacy.

While the procedure carries risks, such as the possible reimplantation of cancer cells, these risks can be reduced through careful biopsies and testing, emphasizing the need for improved safety protocols and standardization in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian tissue preservation, present and clinical perspectives. Jakimiuk, AJ., Grzybowski, W.[2016]

Cryopreservation of ovarian tissue is a promising method for preserving fertility in patients at risk of ovarian failure due to cancer treatments, allowing for future autotransplantation without delaying chemotherapy.

This technique is particularly important for prepubertal girls who have not yet reached sexual maturity, as it is currently their only option for fertility preservation, highlighting the need for collaboration between oncologists and reproductive specialists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ovarian cryopreservation. Jeong, K., Aslan, E., Ozkaya, E., et al.[2021]

References

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

Appropriate Osmotic Balance Duration for Different Volumes of Ovarian Tissue in Vitrification Solution: a Study of Ovary Tissue Vitrification and Transplantation in Sheep. [2018]

2. Iran pubmed.ncbi.nlm.nih.gov

Assessment of ovarian tissues autografted to various body sites followed by IVM in mouse. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of assisted reproductive technology after ovarian tissue transplantation in a cohort of 11 patients with or without associated infertility factors. [2022]

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

Outcomes of transplantations of cryopreserved ovarian tissue to 41 women in Denmark. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Autotransplantation of cryopreserved ovarian tissue--effective method of fertility preservation in cancer patients. [2014]

6. 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]

7. England pubmed.ncbi.nlm.nih.gov

Delaying Reproductive Aging by Ovarian Tissue Cryopreservation and Transplantation: Is it Prime Time? [2022]

8. England pubmed.ncbi.nlm.nih.gov

Safety of ovarian tissue transplantation in patients with borderline ovarian tumors. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Ovarian tissue banking for cancer patients: reduction of post-transplantation ischaemic injury: intact ovary freezing and transplantation. [2022]

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

Ovarian tissue preservation, present and clinical perspectives. [2016]

11. Italy pubmed.ncbi.nlm.nih.gov

Ovarian cryopreservation. [2021]