Ovarian Tissue Cryopreservation for Female Infertility

(OTC Trial)

Overseen By Briana Fodor

Age: < 65

Sex: Female

Trial Phase: Academic

Sponsor: Phoenix Children's Hospital

Disqualifiers: Pregnancy, Breastfeeding, High surgical risk, 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: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ovarian tissue freezing (also known as ovarian tissue cryopreservation) to preserve fertility for girls who might lose the ability to have children due to certain medical treatments. It focuses on those recently diagnosed with or experiencing recurring cancer who will undergo treatments like radiation or chemotherapy that could harm their ovaries. Girls needing one or both ovaries removed due to a health condition are also considered. Those with a medical condition likely to be impacted by their treatment, such as requiring pelvic radiation, might be suitable candidates. As an unphased trial, this study offers participants a unique opportunity to contribute to groundbreaking research in fertility preservation.

Will I have to stop taking my current medications?

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 ovarian tissue cryopreservation is safe for fertility preservation?

Research shows that freezing and storing ovarian tissue, known as ovarian tissue cryopreservation (OTC), is generally safe and well-tolerated. Studies have found it promising for restoring fertility and normal ovary function. Some small studies report successful births after this procedure. Specifically, a review of 568 cases found that 37% of women became pregnant after their ovarian tissue was re-implanted. This suggests OTC can be a good option for girls who need treatments that might harm their fertility. No major reports of problems related to OTC exist, making it a reasonable choice for preserving fertility. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Ovarian Tissue Cryopreservation is unique because it offers a way to preserve fertility in young females who are facing treatments that could lead to infertility, such as certain cancer therapies. Unlike traditional methods like egg or embryo freezing, this technique involves freezing ovarian tissue before the patient undergoes potentially damaging treatments. Researchers are excited because this method allows for the preservation of a larger number of immature eggs, which can be reimplanted later to restore fertility. This approach is particularly promising for girls and young women who may not be able to undergo egg retrieval due to age or treatment urgency.

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

Studies have shown that freezing ovarian tissue can effectively preserve fertility. In one study, 71% of women who attempted pregnancy after this procedure succeeded without needing additional interventions like ovarian transplants or egg donations. This method is particularly beneficial for young girls who have not yet started menstruating and are undergoing treatments that might harm fertility. Success rates for pregnancies using frozen ovarian tissue are comparable to other methods, such as freezing eggs or embryos. This suggests that freezing ovarian tissue is a promising option for those needing to preserve fertility due to medical treatments or conditions. Participants in this trial will undergo ovarian tissue cryopreservation to assess its effectiveness in preserving fertility for girls facing potential infertility due to medical treatments. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for girls who may lose their fertility due to medical treatments like high-dose chemotherapy or pelvic irradiation, and those needing ovary removal due to health conditions. They must be healthy enough for laparoscopic surgery as determined by an anesthesiologist.

Inclusion Criteria

My treatment plan includes high-dose chemotherapy or a bone marrow transplant.

My cancer treatment includes whole abdomen, pelvic, or total body irradiation.

I need surgery to remove one or both ovaries and am healthy enough for surgery.

Exclusion Criteria

Patients who are eligible for and agree to oocyte preservation

Pregnancy or a patient who is currently breastfeeding

I am considered high risk for surgery or anesthesia complications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ovarian Tissue Cryopreservation

Participants undergo ovarian tissue cryopreservation for fertility preservation

2-3 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after ovarian tissue cryopreservation

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Ovarian Tissue Cryopreservation

Trial Overview The study involves the laparoscopic removal of ovarian tissue before starting a treatment that could cause infertility. The removed tissue is then frozen for potential future use in restoring fertility.

How Is the Trial Designed?

Group I: girls facing possible infertility Experimental Treatment 1 Intervention

Newly diagnosed female or relapsed malignancy who is 1-25 years of age with proposed treatment regimen containing at least ONE (1) of the following: whole abdomen or pelvic irradiation total body irradiation Proposed treatment regimen to include any of the following: cyclophosphamide equivalent dose (CED, see Green et al 2014) ≥7.5 g/m2 any treatment regimen containing procarbazine bone marrow transplant conditioning regimen containing alkylator OR health condition or malignancy that requires removal of one or both ovaries

Ovarian Tissue Cryopreservation is already approved in European Union, United States for the following indications:

Approved in European Union as Ovarian Tissue Cryopreservation for:

• Fertility preservation in individuals facing fertility-threatening medical diagnoses or treatments
• Premature ovarian failure prevention

Approved in United States as Ovarian Tissue Cryopreservation for:

• Fertility preservation in individuals facing fertility-threatening medical diagnoses or treatments
• Premature ovarian failure prevention

Who Is Running the Clinical Trial?

Phoenix Children's Hospital

Lead Sponsor

Trials

78

Recruited

5,014,000+

Published Research Related to This Trial

In a study involving 24 nude mice implanted with human ovarian tissues, treatment with Setarud significantly increased vascular density in the transplanted ovarian tissue by day 7 post-transplantation, suggesting enhanced angiogenesis.

Setarud treatment resulted in lower levels of Angiopoietin-1 and higher levels of Angiopoietin-2 and Vascular Endothelial Growth Factor, indicating a potential mechanism for its angiogenic effects in preserving ovarian tissue after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of Setarud (IMOD(TM)) on angiogenesis in transplanted human ovarian tissue to nude mice. Hormozi, M., Talebi, S., Khorram Khorshid, HR., 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]

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 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]

The study found that adding vanadium to the vitrification medium significantly improved the number of healthy-looking follicles in cryopreserved mouse ovaries, indicating better preservation during freezing.

Follicles from ovaries treated with 100 μM vanadium showed higher growth and viability rates compared to those without vanadium, suggesting that vanadium enhances the effectiveness of ovarian cryopreservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation of Vitrification Medium with Vanadium: Evaluation of Histological Change and Follicle Growth. [2019]

Cryopreservation and autotransplantation of ovarian tissue successfully restored menstrual cycles in all six women studied within 14-20 weeks after the procedure, indicating effective ovarian activity post-transplant.

Four out of six women conceived following the procedure, with two delivering healthy children, demonstrating the potential of this technique to preserve fertility even when ovarian tissue is transported prior to freezing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two successful pregnancies following autotransplantation of frozen/thawed ovarian tissue. Andersen, CY., Rosendahl, M., Byskov, AG., 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]

This study demonstrated that immature oocytes can be successfully retrieved from ovarian tissue with minimal preparation before being sent to a cryobank, allowing for effective fertility preservation in women undergoing gonadotoxic therapies.

Out of 12 patients, the maturation rate of the retrieved oocytes was 38.9%, and fertilization rates were promising, indicating that this method can increase the number of viable oocytes available for future fertility treatments without the need for controlled ovarian stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro maturation of immature oocytes from ovarian tissue prior to shipment to a cryobank. Dietrich, JE., Jauckus, J., Hoffmann, S., et al.[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]

A new method for isolating pre-antral follicles from the discarded ovarian medulla has been developed, allowing for the collection of viable follicles from 40 girls and women aged 3-35 years undergoing fertility preservation.

The study found that the medulla contains a significant number of pre-antral follicles, particularly in younger patients, with a total of 3607 follicles isolated, which could enhance fertility preservation techniques and provide opportunities for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of pre-antral follicles from human ovarian medulla tissue. Kristensen, SG., Rasmussen, A., Byskov, AG., et al.[2013]

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]

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]

Citations

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

Ovarian tissue cryopreservation: a narrative review on ... OTC has shown promising results in restoring fertility and the endocrine function of ovaries. Slow freezing and vitrification are two well- ...

2. rbej.biomedcentral.com rbej.biomedcentral.com/articles/10.1186/s12958-025-01388-x

Ovarian tissue cryopreservation for fertility preservation Ovarian tissue cryopreservation (OTC) is the only fertility preservation option for premenarcheal girls before gonadotoxic treatment.

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

To improve outcome after ovarian tissue cryopreservation and ... Ovarian tissue cryopreservation (OTC) has been developed to preserve fertility for women with planned gonadotoxic treatment. It has the ...

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

Efficacy of ovarian tissue cryopreservation for fertility ... In our questionnaire study, 71% of women who tried to conceive succeeded without the need for ovarian transplantation, oocyte donation or cryopreserved embryos.

5. fertstert.org fertstert.org/article/S0015-0282(22)00188-1/fulltext

A comparison of fertility preservation outcomes in patients ... The clinical pregnancy rates were 34.9%, 49.0%, and 43.8% for oocyte, embryo, and ovarian tissue cryopreservation, respectively. No significant ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02678910

Ovarian Tissue Freezing For Fertility Preservation In ... The purpose of this research is to obtain ovarian tissue from female participants who will receive therapy which is expected to result in a loss or impairment ...

7. academic.oup.com academic.oup.com/hropen/article/2017/1/hox001/3092402

Ovarian tissue cryopreservation for fertility preservation Small case series have reported successful live births after ovarian tissue cryopreservation and orthotopic transplantation, ...

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

Practice guideline on ovarian tissue cryopreservation and ... A meta-analysis of 568 cases of post-OTCT fertility assessment showed a 37 % pregnancy rate after cryopreserved ovarian tissue transplantation [19]. However, ...