Ovarian Tissue Cryopreservation for Premature Ovarian Failure

Overseen By Rodriq E. Stubbs, NP

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Menopause, No surgery clearance, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

300 Participants Needed

Trial Summary

What is the purpose of this trial?

The study hopes to contribute to the development of technologies of ovarian tissue freezing-thawing and in vitro maturation of immature eggs such that a person at risk for premature ovarian failure might be able to conceive a genetically related child.

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

The trial protocol 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 data supports the effectiveness of the treatment Cryopreservation of Ovarian Tissue for Premature Ovarian Failure?

Research shows that cryopreservation of ovarian tissue can successfully restore ovarian function, as demonstrated in a case where ovarian function was restored after transplantation of tissue that had been cryopreserved for 10 years. This suggests that the treatment can be effective in preserving ovarian function in patients at risk of premature ovarian failure. ^{1 2 3 4 5}

Is ovarian tissue cryopreservation safe for humans?

Ovarian tissue cryopreservation has been used for over two decades, with thousands of women undergoing the procedure worldwide. While fewer than 500 patients have had their tissue transplanted, nearly all of them regained ovarian function, suggesting the procedure is generally safe. However, there are still risks, such as low follicular survival after thawing and the potential reintroduction of disease. ^{1 6 7 8 9}

How does ovarian tissue cryopreservation differ from other treatments for premature ovarian failure?

Ovarian tissue cryopreservation is unique because it involves freezing ovarian tissue to preserve fertility, which can later be transplanted to restore ovarian function. Unlike other treatments that may focus on hormone replacement, this method directly preserves and potentially restores the natural ovarian function and fertility. ^{1 3 4 5 10}

Research Team

Glenn Schattman, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

This trial is for premenopausal females aged 0-45 who may lose their ovarian function due to cancer treatments or need their ovaries removed. It's also for those who can't or don't want to freeze eggs or embryos but are medically cleared for surgery.

Inclusion Criteria

My treatment may cause early menopause due to radiation, chemotherapy, or surgery.

I have had cancer treatment but my ovaries are still functioning.

I am not planning to freeze my eggs or embryos for future use.

Exclusion Criteria

I haven't been cleared by my doctor for surgery.

I have gone through menopause.

You do not meet the criteria mentioned earlier.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preoperative Assessment

Preoperative sonographic assessment of ovaries, blood sampling, and infectious disease testing

1-2 weeks

1 visit (in-person)

Surgery

Laparotomy or laparoscopy for removal and cryopreservation of ovarian tissue

1 day

1 visit (in-person)

Postoperative Care

Routine postoperative care following ovarian tissue removal

1-2 weeks

1 visit (in-person)

Follow-up

Hormone testing and evaluation of ovarian reserve 6 months to 1 year post-surgery

6-12 months

2-3 visits (in-person)

Treatment Details

Interventions

• Cryopreservation of Ovarian Tissue

Trial Overview The study tests the effectiveness of freezing and thawing ovarian tissue, as well as maturing immature eggs in a lab setting. This could help women at risk of early ovarian failure have genetically related children in the future.

Participant Groups

Group I: Use of high dose chemotherapy Experimental Treatment 1 Intervention

Use of chemotherapy without removal of the disease ovary.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Findings from Research

The addition of anti-apoptotic drugs, specifically sphingosine-1-phosphate (S1P) and Z-VAD-FMK, to the freezing media for ovarian tissue cryopreservation significantly improves the quality and survival of primordial follicles, which are crucial for fertility.

S1P showed immediate benefits in preserving normal and proliferative primordial follicles after 2 days of culture, while Z-VAD-FMK demonstrated similar effects after 6 days, indicating that both drugs can enhance the effectiveness of ovarian tissue preservation for future fertility restoration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival. Henry, L., Fransolet, M., Labied, S., et al.[2018]

In a study of ovarian tissue from 21 patients, researchers found that the density of primordial follicles significantly decreases with age, indicating that older patients may have a lower follicular reserve for fertility preservation.

The analysis revealed a wide variation in follicular density within individual ovarian cortex fragments, suggesting that the distribution of primordial follicles is uneven across the ovarian tissue, which could impact fertility outcomes after cryopreservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries. Schmidt, KL., Byskov, AG., Nyboe Andersen, A., et al.[2019]

Ovarian tissue cryopreservation is an effective method for preserving ovarian function in patients at high risk of premature ovarian failure, as demonstrated in a case involving an 18-year-old woman.

After 10 years, the transplantation of the cryopreserved ovarian tissue successfully restored ovarian function, indicating the long-term viability of this preservation technique.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First transplantation of cryopreserved ovarian tissue in Portugal, stored for 10 years: an unexpected indication. Póvoa, A., Xavier, P., Calejo, L., et al.[2022]

Transporting ovarian cortex cooled on ice for up to 4 hours before cryopreservation allows for the survival of primordial follicles, as demonstrated in a study involving four patients.

After transplantation into immunodeficient mice, surviving follicles were found in all samples, indicating that the method is effective for preserving fertility in patients undergoing treatments that may harm their ovaries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival of primordial follicles following prolonged transportation of ovarian tissue prior to cryopreservation. Schmidt, KL., Ernst, E., Byskov, AG., et al.[2022]

Cryopreserved ovarian cortex tissue can effectively improve or restore female fertility, making it a valuable option for cancer patients recovering from chemotherapy and for women wishing to delay pregnancy.

The chapter outlines the complete process for preparing, transporting, and cryopreserving ovarian tissue, as well as the methods for thawing and implanting it, ensuring the viability of the tissue for future use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreservation and Thawing of Human Ovarian Cortex Tissue Slices. Liebenthron, J., Montag, M.[2021]

Fertility preservation through ovarian stimulation and cryopreservation is generally safe and can be completed in about 2 weeks, without negatively impacting disease severity or long-term survival for patients with serious medical conditions.

Modern techniques allow for high oocyte yield and can be initiated at various points in the menstrual cycle, with over 25% of patients returning to use fertility services later, highlighting the effectiveness of these preservation methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oocyte and embryo cryopreservation before gonadotoxic treatments: Principles of safe ovarian stimulation, a systematic review. Ozcan, MC., Snegovskikh, V., Adamson, GD.[2022]

Ovarian cortex cryobanking has successfully led to the birth of about 20 children worldwide since its introduction in 2004, highlighting its potential as a fertility preservation technique.

Current research aims to improve the survival rate of ovarian follicles after thawing and transplantation, as well as to reduce the risk of disease reintroduction, making this technique more viable for a wider range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Ovarian cryopreservation: what future?]. Mirallié, S., Fréour, T., Barrière, P.[2012]

Ovarian tissue cryopreservation (OTC) has been successfully used for fertility preservation, with nearly 100% of women regaining ovarian function after transplantation of the preserved tissue, based on data from fewer than 500 patients.

OTC is being explored for additional benefits beyond fertility, such as preventing premature ovarian insufficiency and delaying menopause, but further clinical studies are needed to confirm these potential advantages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FERTILITY PRESERVATION: Freezing of ovarian tissue and clinical opportunities. Yding Andersen, C., Mamsen, LS., Kristensen, SG.[2020]

Ovarian tissue cryopreservation is an effective fertility preservation method, particularly for pre-pubertal patients and those with limited time before gonadotoxic treatment, but over 90% of patients experienced reduced ovarian reserve, with 30% developing premature ovarian failure within 5 years.

Despite the risks, including one severe adverse event during anesthesia, the procedure led to successful fertility outcomes, with 33 spontaneous pregnancies and 34 live births reported among post-pubertal patients, indicating its potential as a viable option for young patients facing fertility threats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis. Imbert, R., Moffa, F., Tsepelidis, S., et al.[2022]

Cryopreservation of ovarian tissue offers a promising option for preserving fertility in women at risk of premature ovarian failure, potentially complementing existing methods like embryo or oocyte freezing.

Initial studies have shown that grafts of frozen human ovarian tissue can develop normally in immunodeficient mice, indicating the potential for successful human applications in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cryopreservation of ovarian tissue. Potential "reproductive insurance" for women at risk of early ovarian failure. Wood, CE., Shaw, JM., Trounson, AO.[2007]

References

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

Supplementation of transport and freezing media with anti-apoptotic drugs improves ovarian cortex survival. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Density and distribution of primordial follicles in single pieces of cortex from 21 patients and in individual pieces of cortex from three entire human ovaries. [2019]

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

First transplantation of cryopreserved ovarian tissue in Portugal, stored for 10 years: an unexpected indication. [2022]

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

Survival of primordial follicles following prolonged transportation of ovarian tissue prior to cryopreservation. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Cryopreservation and Thawing of Human Ovarian Cortex Tissue Slices. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Oocyte and embryo cryopreservation before gonadotoxic treatments: Principles of safe ovarian stimulation, a systematic review. [2022]

7. France pubmed.ncbi.nlm.nih.gov

[Ovarian cryopreservation: what future?]. [2012]

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

FERTILITY PRESERVATION: Freezing of ovarian tissue and clinical opportunities. [2020]

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

Safety and usefulness of cryopreservation of ovarian tissue to preserve fertility: a 12-year retrospective analysis. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Cryopreservation of ovarian tissue. Potential "reproductive insurance" for women at risk of early ovarian failure. [2007]