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TODAY’S RESEARCH FOR TOMORROW’S TREATMENTS:
Preserving fertility in women who survive cancer
For additional information on fertility preservation visit
Fertility Preservation for Women or Fertility Preservation for Men .
What are the side effects of oncology treatments?
Premature ovarian failure and infertility is a common side effect of chemotherapy, radiation therapy or ovarian surgery to treat cancer. All these cytotoxic (cell-killing) treatments are non-specific to the cancer and also kill normally dividing cells in other tissues of the body. For example, in preparation for donor bone marrow transplantation, large doses of radiation are given to destroy the patient’s own malignant bone marrow. Other non-bone marrow tissues are also destroyed, including ovarian tissue and the eggs within. Genetic mutations can be introduced into the germ cells as a consequence of cytotoxic therapies and so even if reproduction is possible with these cytotoxin-exposed gametes, it is not recommended.
Why be concerned about fertility preservation when facing cancer?
As the treatment of childhood cancers becomes more effective (90% cure rate with bone marrow transplantation, for instance), quality of life issues such as the ability to reproduce become more pressing. Previously, patients rarely survived to adulthood to be concerned with issues of infertility.
Why are highly successful fertilized egg (embryo freezing) not always an option for cancer patients?
Although cryopreservation (long term freezing) of fertilized eggs and embryos is common and very successful in IVF clinics, these options are often not feasible for single women or children for two reasons. First, in vitro fertilization (IVF) requires several weeks of ovarian stimulation before the IVF procedure which delays cancer treatment. Secondly, a male partner is required to fertilize the recovered eggs before freezing.
Freezing of unfertilized eggs would be the obvious solution but technically, the unfertilized egg is more difficult to cryopreserve.
What are some of the limitiations of current techniques for unfertilized egg freezing?
Cryopreservation of unfertilized eggs remains a research protocol at this time with a very low birth rate. Although babies have been born from previously frozen unfertilized eggs that are thawed and inseminated, the "take-home" baby rate is well below that achievable with fresh eggs. Furthermore, because oocyte cryopreservation is a relatively new area, no data exists regarding long-term effects to the children produced from these previously cryopreserved unfertilized eggs. Studies on oocyte cryopreservation are ongoing at Center for Reproductive Biology of Indiana, LLC. and other infertility centers and may eventually become the standard of care but current techniques are still considered experimental. Patients with other options for reproduction (standard IVF with cryopreservation of fertilized eggs and embryos) should use these proven therapies first. For the oncology patient, special circumstances (type of cancer, absence of a partner, short timeframe before beginning treatment) may make it impossible to use standard treatments. In these situations, oocyte cryopreservation may represent a viable option. Please consult your physician to decide whether more experimental therapies should be considered in your situation.
What about freezing ovarian tissue?
Ovarian tissue freezing and transplantation is under investigation for the preservation of animal species that are faced with extinction or to preserve rare genetically important lab animal strains. Research with animals has shown limited success with recovery of fertility after autotransplantation of ovarian tissue and birth of live offspring in mice and sheep. In contrast, VERY LITTLE data is available in humans. See case report below. Ovarian tissue freezing is being offered under an IRB-approved research protocol at CRBI.
How successful is Ovarian Tissue Cryopreservation and Auto Transplantation in humans?
CASE REPORT:
A 36 year old woman consented to removal of the right ovary and removal of a strip of ovarian tissue from the left ovary before undergoing treatment with high dose chemotherapy to treat a third recurrence of Hodgkin’s lymphoma. The ovarian tissue was cryopreserved and stored for her future use. The patient experienced remission of the cancer but experienced premature menopause. The ovarian tissue was thawed and transplanted back to the patient. Seven months after the transplant, estradiol was detected in her blood, indicating that the ovarian tissue was functional and producing steroid hormone. She experienced a menstrual cycle. Unfortunately, within 9 months, her cycles stopped and steroid production ceased, returning her to a post-menopausal state. However, this initial study demonstrated that it was possible to restore steroid function after cyropreservation and transplantation of ovarian tissue. Obviously, much research is needed to develop medical procedures that are able to fully restore reproductive function in humans. Encouragingly, animal studies on ovarian transplantion have resulted in live births in rats and sheep.
Case report described in full in the medical journal Lancet 2001 Apr 14; 357 (9263):1172-5.
How safe is ovarian transplantation in cancer survivors?
Animal studies have shown that malignant cells present in the untreated rat ovary before transplantation are able to survive cryopreservation and transplantation. These “seed cells” for ovarian cancer were able to grow and spread in the transplant recipient. Obviously this would be catastrophic for a cancer survivor. Research is underway to develop markers of ovarian cancer to detect malignant cells in ovarian tissue before transplantation.
Are there any non-transplant options for cryopreserved tissue?
To avoid the problem of transplantation of malignant cells along with ovarian tissue, research is ongoing to be able to mature eggs in vitro recovered from cryopreserved follicular tissue. Eggs can be recovered from follicles without contamination of other cells, especially possibly malignant ovarian cells and then matured in vitro. Alternatively, whole follicle culture is another experimental method to recover mature eggs that can be used for in vitro fertilization (IVF). See Ongoing Research at CRBI.
Another approach to safeguard reproductive function is directed at prevention of ovarian damage through the use of gonadotropin releasing hormone (GnRH) –analogs to temporarily “shut down” the ovaries during oncology treatment. This therapy is based on the observation that mature women appear to be more sensitive to the cytotoxic effect of chemotherapy compared to pre-pubertal girls. These therapies are experimental and although some success has been demonstrated in animal studies, clinical applications are still experimental. Temporary surgical relocation of the ovaries behind the uterus to afford some physical protection from radiotherapy has also been tried with some success.
Patients should discuss with their physicians the following concerns for their particular circumstances.
- Patient’s risk of sterility from the oncology treatment plan
- Overall prognosis of patient
- Risks due to delaying treatment of cancer for preservation therapies
- Impact of future pregnancy on relapse of cancer
- Effect of hormonal stimulations on the tumor’s growth and malignancy
- Possibility of malignant cells contaminating the removed cryopreserved ovarian tissue
Source of Issues: Seymour, JF. Ovarian tissue cryopreservation for cancer patients: who is appropriate? Reprod Fertil Dev 2001;13(1):81-89.
In some cases, it may not be worth the risk to the patient to pursue reproductive preservation therapies, especially in light of the fact that many of these therapies are experimental. With more research and increasing data on pregnancy outcomes, these decisions may be easier to make for each patient
CRBI participates in the Sharing Hope Program read more about this at their website.
