The Ethics Of Oncofertility

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Louise Brown, the first child born as a result of in vitro fertilization (Image John Loengrad-Time & Life Pictures, Getty Image)

Research and care for cancer have made great progress in the last decade. Many more people survive a once fatal illness, and look ahead to a hopeful future. But the treatment of cancer can have serious side effects, including the possible end of a person’s reproductive life. Most life-saving cancer regimens risk harming or destroying the sperm and eggs needed for normal reproduction. For men, the solution is straightforward—freezing sperm before treatment begins and using it later. But for women, clinical trials involving egg freezing have not been nearly as successful, and there are currently few other options to combat their resulting infertility.

Researchers led by Dr. Teresa Woodruff at Northwestern University and their national collaborators are currently pioneering a new field they’ve termed “oncofertility”—the interdisciplinary approach to preserving a woman’s fertility in the face of cancer. The cornerstone of Woodruff’s research is an experimental procedure in which a woman’s ovarian tissue, rather than her individual eggs, is removed prior to cancer treatments and frozen. It is the hypothesis of the research that when the woman is ready to have a child, the follicles, or immature eggs and their necessary support cells, could be thawed, removed from the tissue and matured, allowing the woman to use her own eggs for IVF. This procedure has already been successful in mouse models, and it may hold great promise for female cancer patients. You can read more about the science of oncofertility in the accompanying article.

However, it also raises a multitude of ethical issues that must be addressed as the research advances. Research on human subjects, particularly women and children, can be controversial, and artificial reproduction and the use of eggs in general raise moral questions. Woodruff’s research will mean careful reflection on very complex and serious problems. How can this research be conducted in a fair and effective way? If the procedure proves successful, should it be limited to cancer patients only, or offered to all women as a safeguard for their future fertility? It is the work of Northwestern University’s Center for Bioethics, Science and Society to study these questions, both about the procedure itself and its place in the broader field of reproductive technology.

While maturing follicles from ovarian tissue in a lab is surely a remarkable concept, non-traditional methods of conceiving and bearing children are not new. Among some of our oldest written histories, including the Hebrew Scripture, are accounts of surrogate mothers and of wet nurses, remarkable pregnancies in elderly women and the use of medications in the process.

Yet, while the path of this research has led logically from its beginnings in the first surrogate mother, this latest step will surely raise significant ethical inquiry. For, if these techniques are as successful in humans as it has now been shown for the mouse, then an unprecedented choice might be available to women and girls—it will be possible to selectively remove an ovary, store the tissue, and recover eggs at a later time for use in in vitro fertilization (IVF), with the ease currently applied to men using frozen sperm for the same purpose. Like men, women could do this long in advance of a relationship with a partner.

The Woodruff lab hopes to look toward clinical trials within the next couple of years, provided that additional animal research continues to yield positive results. Human ovarian tissue will be necessary to conduct this research, and the hope is that the donor may benefit someday from having her tissue stored. The process of acquiring this tissue and deciding how it will be used raises its own set of ethical issues. Many of these are practical questions that will need to be answered as clinical trials begin. For example, what percentage of the stored tissue should be kept for private use versus research to validate the procedure? Who owns the tissue? Who should profit, if anyone?

However, some of the questions are more abstract and less easy to answer definitively. How do we ensure that patients are not unfairly coerced into enrolling in the trial or offered false hope for either the fertility or the cancer therapy? How can vulnerable subjects be assured of continuing access to health care and support, after their tissue is retrieved? What is the nature and meaning of asking permission to do research for a procedure that hold great promise but great uncertainty and whose parameters can continually change as the technology itself is developed?

Deciding who would be eligible for the procedure raises another set of questions. If a physician could accurately predict the likelihood of the patient’s infertility, what percent chance of infertility would be the threshold for a patient to decide to participate in the study? How high would a patient’s infertility risk have to be for a physician to offer them experimental fertility preserving options at all? The difficulty in answering these questions is compounded by the difficulty in predicting infertility for any given cancer treatment regime. The goal of cancer treatment is to cure with the least amount of damage to the rest of the organs in the body—including the delicate structures of the gametes. It is a difficult goal to achieve. The variables of age, chemotherapy and radiation regime, and individual physiology can all influence both the primary outcome of curing cancer as well as secondary outcomes.

Also, the effect of harvesting the ovary or ovarian tissue from the patient must be considered. The procedure requires surgery, some risk, some pain, and a relatively short recovery time, although it does not involve the risk of massive hormonal use that would be needed to mature eggs in preparation for emergency IVF. Should the time and kinds of treatment for the cancer be altered by the harvest of the ovary? For whom is the risk of surgery justified? For whom is the risk of treatment delay justified?

All of these issues become even more complex when the patient in question is a child. For the family confronting cancer in their child, the crisis of survival would likely dominate the discussion. However, unlike many other pediatric interventions, this requires ones’ moral imagination to consider not only the best interests of the child at the present time, but also of the adult person that the child would (hopefully) become in the future. This is a doubled consideration, for in addition to anxiety that the child will not survive, there is the need to both hold and abandon the sense of innocence of children with the violation of surgery and the thought of the child’s future sexual preferences, plans and reproductive life.

Finally, the promise of oncofertility research also requires us to consider if, once the procedure has proven successful, it should be limited to cancer patients alone. This question calls to mind the assumption that a critical part of a human life is the ability to bear genetic children, and the loss of that ability is a medical problem with a medical solution. When does normal aging become a risk factor in the newly framed disease of infertility? The statistics are startling—by age 33, there is a 20-25% risk that all women will need reproductive assistance. Assuming in vitro follicle maturation would allow a woman to conceive by IVF in the future, there could be distinct advantages to storing ovarian tissue in her 20’s. The ovary could be removed when she is sexually mature and in her reproductive prime. Younger ovaries contain more follicles, and they are not yet resistant to the hormones that mature eggs each month. Also, younger eggs are less likely to have chromosomal abnormalities, lowering the risk of genetic errors that lead to genetic diseases. Given the low risk of surgery and an approximately 20-25% risk of infertility later, can she elect to have this surgery at age 25? Should limits be set for this technology’s use in cancer survivors alone? What about for other life-threatening events? If its uses are limited, how could this be done in the climate of IVF and assisted reproductive technology as it now exists, and how should such regulation be defined and maintained?

Now that the first mouse models show success, it is time for a wider consideration of these very real issues in advance of human clinical trials. The first priority must be to the families who will face the choice to pursue this experimental option, and the educational efforts that will be aimed at them. A thoughtful, community-wide education and dialogue should focus on the use of this technology in situations where women face the destruction of fertility.

This may prove difficult, however, for what begins as a therapy for cancer patients could be used quietly in other situations, which may be less desperate, be seen as less reasonable, and have more social implications. At issue will be our ability to set limits on technology in its first years, and how new technology creates meaning by redefining the possible path of any woman’s life—raising issues for some about the nature of limits themselves. Precisely because this research holds the possibility for such expansion, it is important to reflect on these questions long before it is available in the clinic. This research, in fact, has the potential to become one of the largest changes since the birth control pill in how women construct their lives.

An early articulation and expansion of these questions will allow our research in ethics to proceed along with, and not behind, the science as it emerges. I hope that this work will be understood as one more research direction that allows us to consider new human possibilities with thoughtfulness, compassion, and humility.

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