Autologous Ovarian Tissue Transplant for Infertility

Overseen By Jennifer Anglin

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help women who became infertile after cancer treatments like chemotherapy or radiation. It involves transplanting previously frozen ovarian tissue back into the body to determine if it can restore fertility. Known as an autologous ovarian tissue transplant, the goal is to assess the safety and effectiveness of this approach for women with primary ovarian insufficiency (when the ovaries stop working properly before age 40) following cancer treatments. Women who have already had their ovarian tissue frozen and are in good health may be suitable candidates, especially if they wish to become pregnant. As an unphased trial, this study provides a unique opportunity for women to explore innovative fertility restoration methods.

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.

What prior data suggests that this protocol is safe for ovarian tissue transplantation?

Research shows that ovarian tissue transplants are generally safe for humans. Studies have found that this procedure can help women maintain ovarian function after chemotherapy or radiation. One study examined the safety and effectiveness of these transplants and found that about 51% of women became pregnant, and around 33% had a live birth, indicating positive results.

While some studies haven't listed specific side effects, these trials primarily aim to ensure safety and effectiveness. Researchers closely monitor any serious side effects. The fact that many studies are investigating this procedure indicates confidence in its potential safety. Overall, evidence suggests that ovarian tissue transplants are a promising option for women wanting to preserve fertility after cancer treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike other treatments for infertility, which often involve hormone therapy or IVF, ovarian tissue transplant is unique because it uses a patient's own previously frozen ovarian tissue. This approach is particularly exciting because it directly restores ovarian function by reintroducing healthy tissue into the abdomen, potentially leading to natural hormone production and ovulation. Researchers are enthusiastic about this treatment as it offers a more personalized and potentially less invasive alternative to traditional infertility treatments.

What evidence suggests that ovarian tissue transplant might be an effective treatment for infertility?

Research shows that ovarian tissue transplants, the treatment under study in this trial, can help women regain fertility after chemotherapy or radiation. More than 130 babies have been born to women who underwent this procedure. Studies indicate that women who freeze and then transplant their ovarian tissue have similar chances of getting pregnant as those who do not undergo this process. Additionally, ovarian tissue transplants might help restore reproductive hormones. Women under 36 with a healthy number of eggs before freezing their tissue have the best chance of becoming pregnant. ^{1 3 6 7 8}

Who Is on the Research Team?

Kyle Orwig, PhD

Principal Investigator

University of Pittsburgh/University of Pittsburgh Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9239173/

A Systematic Review of Ovarian Tissue Transplantation ... Reported in 2017, ovarian tissue transplantation (OTT) has resulted in over 130 births (11). A recent meta-analysis of three centers has stated a pregnancy rate ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0002937825000869

Pregnancy outcomes following ovarian tissue ... Most women had reported pregnancies by 15 years after ovarian tissue cryopreservation, with transplant cases having a similar overall pregnancy rate.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9733829/

Fresh and cryopreserved ovarian tissue transplantation for ... Ovarian tissue cryopreservation and transplantation may not only be effective in restoring fertility but also the return of reproductive endocrine function.

4. obgyn.onlinelibrary.wiley.com obgyn.onlinelibrary.wiley.com/doi/10.1111/jog.70080

To improve outcome after ovarian tissue cryopreservation and ... Our findings suggest pregnancy chances after OTT are highest in patients <36 years of age, with normal ovarian reserve at the time of OTC, who ...

5. rbej.biomedcentral.com rbej.biomedcentral.com/articles/10.1186/s12958-023-01167-6

Assessing the impact of transplant site on ovarian tissue ... Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11–36, I2: 0.00%, fixed effect).

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39173181/

Utility and Outcomes of Ovarian Tissue Cryopreservation and ... Our results suggest that ovarian tissue cryopreservation and autologous transplantation are feasible options for preserving ovarian function in women with ...

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT01870752

NCT01870752 | Ovarian Tissue Transplantation The primary objective of this study is to determine the efficacy and safety of autologous transplantation of previously cryopreserved ovarian ...

8. sciencedirect.com sciencedirect.com/org/science/article/pii/S0204804323000489

Safety and efficacy of ovarian tissue autotransplantation Ovarian transplantation was associated with a pregnancy rate of 50.7% and a live birth rate of 32.7% per patient. Growing follicles are the most vulnerable to ...