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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a method to help women regain fertility after cancer treatments such as chemotherapy or radiation. The focus is on transplanting previously frozen and stored ovarian tissue, known as ovarian tissue transplantation, to determine if this method can safely restore the ability to conceive. Suitable candidates are women who have stored their ovarian tissue, face difficulties conceiving after cancer treatment, and have tried to conceive for at least six months without success. As an unphased trial, this study provides a unique opportunity for women to explore innovative fertility restoration methods.

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

Research has shown that ovarian tissue transplantation is generally well-tolerated. In one study of 568 cases, 37% of women became pregnant after the procedure, indicating its effectiveness for many. Another study found pregnancy rates as high as 81.3% with certain methods, demonstrating success in restoring fertility.

Regarding safety, the technique shows promise for preserving ovarian function. Although these studies do not detail specific side effects, the consistent use and success rates suggest that serious problems are rare. The treatment's success in restoring fertility offers hope for those facing infertility after cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ovarian tissue transplantation for female infertility because it offers a novel approach by using cryopreserved ovarian tissue. Unlike traditional treatments like hormone therapy or in vitro fertilization, this method involves surgically transplanting ovarian tissue that was collected and frozen earlier. This unique approach has the potential to restore natural hormone function and fertility, possibly offering a more holistic and long-term solution for women who have undergone treatments that affect fertility, such as chemotherapy. This method could be particularly beneficial for women who wish to conceive naturally or those who have had their fertility compromised due to medical treatments.

What evidence suggests that ovarian tissue transplantation is effective for female infertility?

Research has shown that freezing and then transplanting ovarian tissue can help women regain fertility after cancer treatments. Studies have found that many women who underwent this procedure became pregnant, with some groups reporting success rates as high as 81.3%. One study showed a 37% pregnancy rate using frozen ovarian tissue. These findings suggest that the procedure can help restore fertility. In this trial, participants will save ovarian tissue before cancer treatment and have it transplanted back afterward to help the ovaries function again. ^{1 2 5 6 7}

Who Is on the Research Team?

Clarisa Gracia

Principal Investigator

Abramson Cancer Center at Penn Medicine

Are You a Good Fit for This Trial?

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

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

Current pregnancy

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

Citations

1. 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 ...

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/PMC9239173/

A Systematic Review of Ovarian Tissue Transplantation ... All participants had ovarian tissue cryopreserved by slow freezing. The pregnancy rate was 81.3%, 45.5%, 66.7% in the strips, squares, fragment groups, ...

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

To improve outcome after ovarian tissue cryopreservation and ... Determinants of transplantation success with cryopreserved ovarian tissue: data from 196 women of the FertiPROTEKT network. Hum Reprod. 2022 ...

5. academic.oup.com academic.oup.com/humupd/article/28/3/400/6535334

Fresh and cryopreserved ovarian tissue transplantation for ... The pregnancy rate for frozen transplants was 37% (95% CI: 32–43%) and for fresh transplants was 52% (95% CI: 28–96%). Some women achieved more than ...

6. 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 ...

7. 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, ...