Ovarian Tissue Transplantation for Female Infertility

Overseen By Clarisa Gracia, MD

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Abramson Cancer Center of the University of Pennsylvania

Disqualifiers: BRCA mutation, Leukemia, Ovarian cancer, 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

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Ovarian Tissue Transplantation for Female Infertility?

Research shows that ovarian tissue transplantation, which involves using previously frozen ovarian tissue, has resulted in the birth of six babies worldwide. Additionally, over 170 births have been reported following similar procedures in women who underwent cancer treatments, indicating its potential effectiveness in restoring fertility. ^{1 2 3 4 5}

Is ovarian tissue transplantation safe for humans?

Ovarian tissue transplantation has been performed in many cases with a low risk of complications, similar to standard laparoscopy (a type of minimally invasive surgery). Out of 1373 procedures, only three had complications, and the procedure has led to successful pregnancies and births, indicating it is generally safe. ^{2 3 5 6 7}

How is ovarian tissue transplantation different from other treatments for female infertility?

Ovarian tissue transplantation is unique because it involves transplanting a woman's own previously frozen ovarian tissue to restore fertility, which is particularly useful for women who have undergone cancer treatments that affect fertility. Unlike other fertility treatments, this method can also restore natural hormone production and has resulted in successful pregnancies and births. ^{1 2 3 4 5}

What is the purpose of this trial?

Chemotherapy and radiation therapy for the treatment of cancer can compromise fertility. Ovarian tissue cryopreservation is an experimental strategy offered at The University of Pennsylvania to preserve future fertility (protocol 806062). The primary objective of this study is to determine the efficacy and safety of autologous transplantation of previously cryopreserved ovarian cortical tissue in patients who experience infertility or ovarian insufficiency after cancer treatments.

Research Team

Clarisa Gracia

Principal Investigator

Abramson Cancer Center at Penn Medicine

Eligibility Criteria

This trial is for women aged 18-45 who have become infertile or have ovarian insufficiency due to cancer treatments. They must have their own frozen ovarian tissue, be in good health, and unable to conceive naturally after trying for 6 months. Women with high surgical risk, current pregnancy, BRCA mutation, certain cancers or mental conditions affecting consent are excluded.

Inclusion Criteria

Ovarian insufficiency defined as an elevated FSH over 10

Inability to conceive after 6 months of unprotected intercourse with male

Reasonably good health

Exclusion Criteria

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

Women with psychological, psychiatric, or other conditions which prevent giving fully informed consent

Current pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Surgical transplantation of previously collected cryopreserved ovarian cortical tissue

1 week

1 visit (in-person)

Follow-up

Participants are monitored for surgical complications and effectiveness of transplantation

5 years

Regular visits as per protocol

Treatment Details

Interventions

• Transplantation of previously cryopreserved ovarian tissue

Trial Overview The study tests the safety and effectiveness of transplanting a woman's own previously frozen ovarian tissue back into her body. This aims to restore fertility in those affected by infertility or ovarian failure post-cancer treatment.

Participant Groups

Group I: Transplantation of previously cryopreserved ovarian tissue Experimental Treatment 1 Intervention

Surgical transplantation of previously collected cryopreserved ovarian cortical tissue.

Transplantation of previously cryopreserved ovarian tissue is already approved in United States, European Union for the following indications:

Approved in United States as Ovarian Tissue Transplantation for:

• Infertility due to cancer treatments
• Ovarian insufficiency due to cancer treatments

Approved in European Union as Ovarian Tissue Transplantation for:

• Fertility preservation in cancer patients
• Restoration of ovarian function after chemotherapy or radiation therapy

Who Is Running the Clinical Trial?

Abramson Cancer Center of the University of Pennsylvania

Lead Sponsor

Trials

360

Recruited

108,000+

Abramson Cancer Center at Penn Medicine

Lead Sponsor

Trials

425

Recruited

464,000+

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]

Ovarian tissue transplantation is currently the only clinical method to restore fertility using cryopreserved tissue, with six successful births reported worldwide, highlighting its potential efficacy.

Factors such as the patient's age and the site of transplantation significantly affect follicular survival, and while various treatments like antioxidants and growth factors have been explored to enhance this, their effectiveness in promoting fertility is still uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orthotopic and heterotopic ovarian tissue transplantation. Demeestere, I., Simon, P., Emiliani, S., 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]

This case marks the first successful retransplantation of cryopreserved ovarian tissue in a cervical cancer patient in Austria, demonstrating the potential for restoring hormone production and fertility after cancer treatment.

The retransplanted ovarian tissue showed proper function within three months, evidenced by hormonal levels and the presence of vital follicles, highlighting the efficacy of this method for fertility preservation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Case Report: Heterotopic Retransplantation of Cryopreserved Ovarian Tissue after Adenocarcinoma of the Uterine Cervix]. Lipovac, M., Herzog, J., Imhof, M.[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]

Laparoscopic removal and transplantation of ovarian tissue for fertility preservation in cancer patients have a very low complication rate, with only three complications reported out of 1373 procedures (0.2%).

After transplantation, 81% of women resumed menstruation, and 16 pregnancies were achieved in 14 patients, indicating that this method is effective for restoring fertility post-cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue. Beckmann, MW., Dittrich, R., Lotz, L., et al.[2018]

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. England pubmed.ncbi.nlm.nih.gov

Orthotopic and heterotopic ovarian tissue transplantation. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. Austria pubmed.ncbi.nlm.nih.gov

[Case Report: Heterotopic Retransplantation of Cryopreserved Ovarian Tissue after Adenocarcinoma of the Uterine Cervix]. [2022]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Fertility protection: complications of surgery and results of removal and transplantation of ovarian tissue. [2018]