PORF awarded this grant to Hanna Valli, Ph.D. and Kyle Orwig, Ph.D. to expand the study of male cryopreserved testicular tissue. The following report identifies the results of this research to date.
An oocyte-derived biomaterial provides a “sperm safe” to preserve mammalian spermatozoa
Cancer treatments such as radiation, chemotherapy, and surgery, while life preserving, can threaten fertility. Fertility preservation in males with conditions of extremely low numbers of germ cells is difficult (e.g. cryptozoopsermia or testicular/epididymal biopsy samples). Fortunately, with intracytoplasmic sperm injection (ICSI), fertility can be restored with technically only a single sperm. Despite the success of ICSI, a significant challenge is the lack of robust and reliable methods to store and recover small numbers of sperm. Through the generous support of the Pediatric Oncofertility Research Foundation and the Daniel J. Manella Research Grant, Dr. Francesca Duncan, PhD in collaboration with Dr. Hoi Chang Lee, PhD (Northwestern University) engineered an oocyte-derived biomaterial – the zona pellucida (ZP) – to function as a “sperm safe” for storing sperm, and we validated the efficiency and efficacy of this method for cryopreservation, storage, and recovery. The ZP is a coating that surrounds the mammalian oocyte. Dr. Duncan and Dr. Lee used a decellularization process to remove cellular material from the ZP, leaving behind a purified scaffold. Decellularization is an established method in biomedical engineering for generation of artificial organs and tissue regeneration purposes. The application of decellularization of the zona pellucida has not been described and represents a major advance in the ability to apply this technology clinically to store small numbers of sperm. This discovery could have significant impact on Assisted Reproduction Technologies in the fertility preservation setting and beyond.
Image of three mouse sperm heads stored in a purified ZP
The attached video was presented at the opening meeting of the International Oncofertility Consortium Conference at Northwestern University, Chicago. This video speaks to the critical role hormone/fertility preservation plays in the quality of life for children treated for cancer. Dr. Woodruff’s powerful statement about the availability of hormone/fertility options for all individuals treated for cancer could not have been made ten years ago. Hormone/fertility preservation for cancer survivors is no longer simply a “hope.” It is a reality. For this reason, PORF strongly believes that a fertility consultation must be the standard of care for all children diagnosed with cancer, regardless of age.
3-D Ovary Research Brief
When I first heard the term “artificial ovary,” I became more than a little wary of the idea. The first images to enter my mind were test tubes with embryos growing outside a human body. As a Christian with very clear beliefs about life from inception to death, I immediately wondered what our organization was potentially supporting. After a quick review, I not only calmed, but became wildly enthusiastic about the promise of this research.
The research is complicated. However, the essence is easily grasped and potentially hopeful. In this brief, PORF will give parents the rudiments of the research and share its potential ramifications for fertility preservation in children treated for cancer.
First of all, the 3-D Ovary is not an artificial monstrosity that creates babies in some contraption disconnected from natural embryo development. Rather, it is a “scaffold” that allows for the introduction of previously removed ovarian tissue to be naturally restored in the female body. This “prosthetic ovary” is designed to allow cryo-preserved ovarian tissue to be used naturally by the donor patient. Think of it as a tiny structure that holds the tissue in place so that it can naturally perform the function for which it was intended.
It is important to note at this juncture that the preservation of ovarian tissue is important for far more than enabling childbirth. Natural hormones for general health for puberty and beyond are contained in ovarian tissue. Once this tissue has been preserved, it has the potential for significantly influencing the health of the patient throughout her life. The 3-D ovary has the potential for enabling this potential in a safe, long-term manner. For this reason, it is important to think of both fertility and hormone preservation when considering ovarian tissue preservation for the cancer patient.
Second, the 3-D Ovary has the potential to benefit those girls whose cancer was systemic in nature. While malignant cells from contained, solid tumor cancers are not present in the cryo-preserved ovarian tissue, there is much less certainty in systemic cancer types. For example, Leukemia patients may well have malignant cells in their ovarian tissue at the time it is removed. This creates a particular issue for the use of that tissue after treatment. The 3-D Ovary holds hope for using only healthy follicles (follicles are the main functional units of the ovary; one follicle contains one potential egg cell surrounded by several hormone-producing cells) from the preserved tissue. Follicles could be removed from the rest of the tissue, thus cleansing it of cancer cells before introducing it into the patient.
Third, the 3-D Ovary has the potential to extend the life of the tissue being introduced into the treated patient. At this time, there is a limit to the time replaced ovarian tissue is functional. With the synthetic ovary, there is hope that the time frame can be significantly extended. This would be especially important to the young girl who needs to use hormone preservation to initiate natural puberty; to stop premature menopause, or to support general health throughout her lifetime.
Fourth, the 3-D ovary is not a device that will cause rejection in the recipient. Unlike some transplants, the 3-D Ovary may not require anti-rejections drugs to be taken by the recipient. Surely, any need to use such drugs complicates the decision to use a transplant. The goal of any hormone/fertility preservation is the natural use of preserved tissue. Therefore, having a device that does not cause additional drugs is a major benefit.
Throughout this brief, I have used tentative terms in speaking of the “potential” of the 3-D Ovary. This is important for parents and patients to appreciate. The prosthetic ovary remains in research development. It has been successful in mice and will soon be tried in other mammals. Human trials are a few years in the future. This means that for those girls who will be ready to use their preserved tissue within the next few years, direct implant is the best solution. Surgeons have been successful using this tissue for hormone restoration and for pregnancy. It is a fine solution for young women who are experiencing compromised hormone development, or inability to become pregnant as a result of cancer treatment.
That being said, the 3-D Ovary may prove to be a better option in time. 3-D Ovary recipients may be able to make extended use of their preserved tissue. They may be able to use follicles extracted from that tissue, instead of the whole tissue. They may be able to have a more natural use of the tissue over a lifetime.
In short, my knee jerk negative reaction to the idea of an artificial ovary has been completely allayed. This research development is significant and worthy of significant funding. PORF will do whatever possible to support this research in the hope of making hormone and fertility preservation the expectation of every young girl treated for cancer.
“Drug could prevent infertility in cancer patients”
This article speaks to a potential treatment for male fertility in cancer patients. While found by accident, this early study may well be an alternative to currently used methods for male fertility preservation. PORF is interested in the potential for such drug treatment to benefit boys, especially pre-pubertal boys. Obviously, it is too early to expect an answer to the question: will this drug allow pre-pubertal boys to retain fertility after cancer treatment?
PORF will follow this research and keep readers informed about its progress.
Daniel J. Manella, Jr. Research Grant
As indicated above, PORF is seeking research proposals that are focused on the best uses of cryo-preserved ovarian and testicular tissue from pre-pubertal children. Additionally, those researchers who are seeking ways to remove malignant cells from preserved tissue are also encouraged to make application.
- Applications should be prepared on official letterhead, indicating the institution that will be sponsoring the research study.
- For ongoing research, applicants should present a copy of the original research proposal, including the approved IRB proposal, and demonstrate the degree to which the study has been completed.
- For new research, applicants should present a copy of the IRB application and a projected timeline for IRB approval. Grant payout will not begin until IRB approval has been granted.
- Applicants should provide a statement of how this grant will further their research agenda.
- Applicants should provide a detailed statement indicating how their institution will promote the work of the Pediatric Oncofertility Research Foundation.
- Applicants should provide a curriculum vita, which includes publications and presentations. Contact information, including a direct phone number, should be included.
Application must be presented in hard copy, or electronically to one of the following address no later than March 1, 2017:
1000 North East Avenue
Oak Park, IL 60302
The Daniel Manella Research Grant will be announced on March 10, 2017. All applicants will receive official notice in advance of the public grant announcement.
All applications for the Daniel J. Manella, Jr. Research Grant will be reviewed by the PORF Review Board. Members of the review board can be found on the Pediatric Oncofertility Research Foundation Website, www.porf.org.
Applicants should feel free to contact Timothy F. Brown, Ed.D. for additional information:
Pediatric Oncofertility Research Foundation
The Daniel J. Manella, Jr. Research Grant
The Pediatric Oncofertility Research Foundation (PORF) is requesting proposals for its first $10,000 Research Grant. The Daniel J. Manella, Jr. Research Grant will be awarded to a researcher who is searching for ways to best use cryo-preserved ovarian, or testicular tissue from pre-pubertal children. The recent report of a child born as a result of cryo-preserved ovarian tissue gives great hope to patients and parents of pediatric cancer patients. However, research is far from complete. Such research questions as: when is the best time to replant preserved tissue; what is the most efficient and efficacious way to replant preserved tissue; can preserved tissue be implanted to maintain hormone levels into adulthood, will require further study. Also, ways to remove cancer cells from preserved ovarian and testicular tissue will be required before cryo-preservation becomes a widespread solution to hormone and fertility preservation in all children with cancer.
Application requirements for the Daniel J. Manella, Jr. Research Grant are posted on www.porf.org. Grant applications must be received by March 1, 2017. Awards will be announced on March 10, 2017.
While the Daniel J. Manella, Jr. Research Grant will be the first to be awarded by PORF in March, another grant will be announced shortly thereafter. Applicants for the Daniel J. Manella, Jr. Grant will also be eligible for the second grant to be awarded in early summer, 2017.
PORF is grateful to the many individuals who have made these research grants possible. No donation amount is too small to make a difference. Be assured that all PORF administrative costs are borne by the founding family. Every dollar donated to PORF by non-family members goes entirely to research.
Please find attached a link to a short, albeit important article that appeared this week in the Chicago Tribune. For some time, researchers have been able to extract and preserve sperm from post-pubertal boys, even those who have just reach puberty. However, the use of undeveloped cells from pre-pubertal boys has been far more of a conundrum. Even though the harvesting of these cells is being completed at several hospitals in the United States, no pathway to using the cells has been determined. From this article, I gather that the pathway may be a work in progress, finally blessed with a patent that will allow its inventors to make it worth their while to extend the research.
Clearly, the term “Pediatric Oncofertility,” does not appear in this article. However, this finding holds hope for pre-pubertal cancer patients who need so desperately to be included in fertility preservation research.
Be assured that PORF will be investigating the work being done in the French lab in cooperation with the French government. If we discover more information, we will share it with you in a timely fashion.