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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on helping individuals at risk of premature ovarian failure, where the ovaries stop functioning earlier than usual. It examines ovarian tissue cryopreservation, a treatment that involves freezing ovarian tissue to potentially aid future conception. This trial suits premenopausal women undergoing treatments, such as high-dose chemotherapy, that could lead to premature menopause. Participants should be unable or unwilling to use other fertility preservation methods, like freezing eggs or embryos. As an unphased trial, it provides a unique opportunity to explore innovative fertility preservation methods.

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 prior data suggests that ovarian tissue cryopreservation is safe for use in individuals at risk for premature ovarian failure?

Research has shown that freezing ovarian tissue can help develop healthy follicles, which are important for fertility. Studies have found that patients generally tolerate this process well. For instance, one study found that about 31.5% of patients who had their ovarian tissue frozen experienced premature ovarian failure, where the ovaries stop working before age 40. This indicates that nearly 68.5% did not face this issue, suggesting the procedure might be safe for many.

Research has not commonly reported any serious side effects related to this treatment. However, like any medical procedure, some risks may still exist. It is important to discuss any concerns with healthcare professionals and consider the potential benefits and risks before deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ovarian tissue cryopreservation for premature ovarian failure because it offers a groundbreaking way to preserve fertility. Unlike standard treatments that may involve hormone therapies or egg donation, this method involves freezing ovarian tissue before high-dose chemotherapy. This allows for the possibility of restoring natural ovarian function and fertility after treatment, providing a unique opportunity for women who face infertility due to cancer therapies. The potential to retain the body's natural reproductive abilities post-treatment is what sets this approach apart and drives the enthusiasm in the research community.

What evidence suggests that ovarian tissue cryopreservation is effective for premature ovarian failure?

Research has shown that freezing and storing ovarian tissue provides about a 30% chance of pregnancy after reimplantation. This method benefits women who might lose fertility due to treatments like chemotherapy. While assessing its full effectiveness can be challenging, this option remains available for those at risk of early ovarian function loss. It allows women to maintain the possibility of having a genetically related child in the future. This technique ranks among the best for preserving fertility when other options, such as egg freezing, are not feasible. Participants in this trial will undergo ovarian tissue cryopreservation to evaluate its effectiveness in preserving fertility for those undergoing high-dose chemotherapy. ^{2 4 6 7 8}

Who Is on the Research Team?

Glenn Schattman, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28333228/

Efficacy of ovarian tissue cryopreservation for fertility ... Our findings confirm a 30% pregnancy rate after ovarian cortex autotransplantation but also stress the difficulties of evaluating the real efficacy of OTC.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0378512224000173

Practice guideline on ovarian tissue cryopreservation and ... Ovarian tissue cryopreservation and transplantation are the most promising methods to preserve the ovarian function and fertility for women who cannot delay ...

3. mdpi.com mdpi.com/2075-1729/14/3/393

Ovarian Tissue Cryopreservation versus Other Fertility ... This systematic review aims to improve understanding of gonadotoxic effects of chemoradiation therapy in cancer patients.

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

To improve outcome after ovarian tissue cryopreservation and ... Moderate-high (>50%) risk for development premature ovarian insufficiency; No possibility for oocyte/embryo cryopreservation; Minimal risk for ...

5. jpagonline.org jpagonline.org/article/S1083-3188(22)00353-9/abstract

Effects of Ovarian Tissue Cryopreservation on Primary ... To determine if removing an ovary for ovarian tissue cryopreservation (OTC) increased rates of primary ovarian insufficiency (POI) in girls ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12130658/

Ovarian tissue cryopreservation: a narrative review on ... Herein, we describe the most recent reported clinical results related to the efficacy and safety of OTC in developing functional follicles, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01558544?term=fertility

NCT01558544 | Cryopreservation of Ovarian Tissue Treatment plan that will likely result in premature menopause or premature ovarian failure; This includes patients receiving: Cancer treatment with abdominal ...

8. academic.oup.com academic.oup.com/humrep/article/32/5/1046/3058833

Efficacy of ovarian tissue cryopreservation for fertility ... In our cohort of patients who underwent OTC, premature ovarian failure (POF) rates, return rates and pregnancy rates after autotransplantation were 31.5, 4.4 ...