Fertility Preservation for Women

Fact: Treatments for cancer and other diseases (eg. lupus, rheumatoid arthritis and Crohn’s disease) may result in subfertility or infertility.

Which cancer therapies can affect fertility?

Chemotherapy that is most likely to damage the ovaries are “alkylator” types such as Cyclophosphamide (Cytoxan), Ifososfamide, Lomustine (CCNU), nitrogen mustard (Mechlorethamine, busulfan, Carmustine (BCNU), Chlorambucil, melphalan, Procarbazine , Thiotepa. And Heavy metals (Carboplatin, Cisplatin), and non-classical alkylators (Decarbazide (DTIC) and Temozolomide)

Radiation can damage reproductive function in several ways:

1. Directly if the radiation is directed at the ovaries (primary failure) or
2. Indirectly if the radiation is aimed at the brain and damage occurs to the pituitary gland which regulates ovarian function (secondary failure) .
3. Pelvic radiation can also damage the vasculature of the uterus and make carrying a pregnancy difficult or impossible.

Surgery. Removal of both ovaries (bilateral oophorectomy) causes “surgical menopause” and infertility. Removal of one ovary can cause premature menopause and subfertility.

What are some common side effects from these therapies?

Chemotherapy, radiation and surgery to remove one or both ovaries can damage the ovaries by decreasing the number of eggs and/or damaging the ovaries’ ability to make the hormones it needs to function normally.

Specifically, side effects of these therapies include:

• In pre-pubertal girls, puberty can be delayed or fail to occur. Hormones may need to be prescribed to induce puberty.
• Failure to have menstrual cycles (can be temporary or permanent)
• Failure of the ovaries to make hormones needed for normal reproductive function; can be treated with hormonal medications.
• Infertility. Infertility is a complex disease and can be caused by other factors aside from cancer therapy. However, cancer therapy certainly increases the risk that a woman will not be able to have a family when she desires a family. In some cases, she may be subfertile, or if she has only one ovary, may experience an earlier menopause (and shorter reproductive window) than she would otherwise experience.
• Pregnancy risks: Even if pregnancy occurs, women who have had cancer therapies may be at increased risk of miscarriage, premature delivery or problems during labor.

When should I address these concerns with my oncologist?

The best time to discuss these concerns is before any cancer therapies are initiated! Once therapies are initiated, damage is done and fertility preservation is no longer an option. Programs like Sharing Hope, through Fertile Hope, provide financial assistance for fertility preservation but only to patients who have not initiated treatment for the cancer. The reason for this policy is that fertility preservation is not likely to be effective once the ovaries are damaged. The American Society of Clinical Oncology (ASCO) has published the following guidelines for oncologists:

“As part of education and informed consent prior to cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists. Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged. Sperm and embryo cryopreservation are considered standard practice and widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise.”

Source: American Society of Clinical Oncology Recommendations on Fertility Preservation in People Treated for Cancer. Guidelines were authored by Stephanie J. Lee, Leslie R. Schover, Ann H. Partridge, Pasquale Patrizio, W. Hamish Wallace, Karen Hagerty, Lindsay N. Beck, Lawrence V. Brennan, Kutluk Oktay

Our experience from patients seeking fertility preservation therapies is that often the patients must bring the topic up with their oncologists if future fertility is a concern to them. In some cases, the cancer may be advanced enough that your oncologist may not recommend a delay in treatment to accommodate fertility preservation, but you will have had the opportunity to discuss your options.

What fertility preservation procedures are available for women at CRBI and how effective are they?

Embryo Banking (also called Emergency IVF): The procedures used are, in most cases, identical to in vitro fertilization (IVF) procedures used for infertility patients. IVF has been performed for over two decades and is no longer considered an experimental procedure. A million babies have been born worldwide from IVF and current success rates exceed a 50% take home baby rate at CRBI. A period of several weeks is needed to undergo the hormonal stimulation necessary for recovery of mature eggs from the patients. In some cases, more immediate cancer therapy is required and fertility preservation by emergency IVF may not be possible, because cancer treatment can’t be delayed. The patient must be healthy enough to tolerate hormonal stimulation of the ovaries and recovery of eggs by transvaginal ultrasound guided egg retrieval. Because retrieved eggs are then fertilized with sperm, the patient must be an adult and have male partner or be willing to use donor sperm. The fertilized eggs are then frozen immediately or cultured to a later stage (blastocyst) and then frozen. Embryos stored in liquid nitrogen are viable for decades. When the patient is in remission, usually after 5 years, thawing of the embryos and transfer can be performed to try to initiate a pregnancy.

Oocyte Banking: This option is very similar to emergency IVF, in that the patient must be able to delay cancer treatment and tolerate hormonal stimulation of the ovaries and ultrasound guided egg retrieval. The main difference is that the recovered oocytes are immediately frozen as unfertilized eggs. In the future, when the patient is ready, the eggs would be thawed and in vitro fertilization would be required to produce embryos which can them be transferred to the patient to start a pregnancy. The disadvantage of this protocol is that the pregnancy rate for using thawed oocytes for IVF is lower than when fresh oocytes are used for IVF. Where you might anticipate a 50% pregnancy rate with thawed embryos, your pregnancy rate might be half that when oocytes are thawed and used for IVF. Rates are improving as clinics gain more experience with these protocols but compared to IVF, egg banking is experimental and ASRM recommends it be offered to patients under an IRB approved protocol.

Oocyte banking is performed at CRBI under an IRB approved protocol (IRB#05-013: Emergency Cryobanking and Future Reproductive Use of Oocytes from Cancer Patients).

Financial Aid through our Oocyte Banking Partnerships: For oncology patients who wish to bank oocytes, we are partnering with Fertile Hope. The Lance Armstrong Foundation and Serono in the Sharing Hope Program for Women The purpose of the Sharing Hope Program is to provide eligible patients with free ovarian stimulation drugs and reduced lab and physician fees to make oocyte banking financially easier for oncology patients. This program does not apply to tissue banking.

Ovarian Tissue Banking: Ovarian tissue banking is the most experimental of the banking options and only a few live births have been reported from banked samples and those few births have occurred from temporary restored menstrual cycling when ovarian tissue was transplanted back into the patient. Most of the births have been from fresh autologous grafts (twin to twin grafts) of fresh tissue. Given the highly experimental nature of ovarian tissue banking, it is the option of choice only for those patients who are not eligible for more effective treatments. Patients for whom ovarian tissue banking is the only banking option include pediatric patients and patients who can’t delay cancer treatment for several weeks but must begin oncotherapy within days. Because fertility preservation from tissue banking is really at the research stage, it is unlikely that older women will benefit. Pediatric patients who can afford to wait a decade or two before starting a family are most likely to see a benefit from tissue banking, because researchers expect to have more effective methods to use the ovaries in the future. For instance, some researchers are looking at using the banked tissue as a starting point for cultivation and maturation of the oocytes in the tissue for use in IVF. Younger patients, particularly pediatric patients, have more eggs stored in their tissue. The number of eggs in the tissue decreases steadily as women age which is another reason that tissue banking is most likely to be useful in the younger patient. Culturing ovarian tissue to mature eggs is called Infollicular Maturation or IFM and is one of the studies that the National Institutes of Health has funded through the Oncofertility Consortium. Recently, CRBI has been accepted as a member of the National Physician’s Cooperative (NPC), which is an organization of fertility doctors who are working with NIH funded researchers at the Oncofertility Consortium. Read more about this below.

The table below shows the three main banking options for women that are offered at CRBI and some of the pros and cons of each approach. Not every patient will have every option available. This table is meant as a starting point for discussions with your physicians, oncologists and fertility specialists as to the best option for your specific circumstances. Ask your oncologist and reproductive endocrinologist about other non-banking options such as surgically moving the ovaries out of the radiation field or use of Lupron to “shut down” the reproductive axis prior to treatment. These options have their own limitations and are controversial as to effectiveness but are mentioned as alternatives to banking options.

Fertility Preservations Available to Girls and Women

All of these banking options are offered through CRBI. CRBI will request that the patient sign an Agreement for Storage contract that contains advance directives for the future disposition of the stored oocytes or embryos. CRBI can not store a specimen unless we have a storage contract on file.

Please call Dr. Wegner at CRBI for more information about these options and to set up an appointment with one of our infertility doctors who will work with your oncologist to coordinate your cancer and fertility preservation treatments.

Exploring and expanding options for the reproductive future of cancer survivors.

New for 2009! CRBI has been accepted as a member of the National Physicians Cooperative (NPC) of the Oncofertility Consortium to provide the most advanced ovarian tissue banking protocols to our patients.

What is the Oncofertility Consortium?

The Oncofertility Consortium is a group of fertility preservation researchers working at four core institutions (Northwestern University/Children’s Memorial Hospital at Chicago, Illinois, University of California at San Diego , California, University of Missouri and University of Pennsylvania-Children’s Hospital of Philadelphia, PA.). This group was awarded a multi-million dollar NIH research grant specifically to translate fertility preservation research to the clinical bedside. The National Physician’s Cooperative is a national group of infertility physicians who are willing to work with the Oncofertility Consortium to provide fertility preservation treatments to oncology patients.

The NPC provides access to human ovarian tissue through patient enrollment in ovarian tissue research and a collaborative forum for the exchange of ideas, clinical research methods, and technologies in order to drive breakthroughs in basic reproductive physiology that will be translated directly to clinical medicine. The NPC is currently comprised of 4 core institutions and over 50 allied health care centers across the country.

The NPC is led by Jeffrey Chang, M.D., Director of the Division of Reproductive Endocrinology at the University of California, San Diego and Marybeth Gerrity, Ph.D., Executive Director of the Oncofertility Consortium.

NPC Membership

The NPC seeks member institutions that can cultivate strong working relationships between their oncology and reproductive endocrinology provider communities and that are committed to participation in NPC clinical research studies.

As a member of NPC, CRBI has agreed to

• Participate in NPC studies under the approval of our own institutional IRB
• Follow all NPC protocols and procedures precisely as described
• Share data with the NPC and abide by its guidelines for publication and commercialization
• Inform patients regarding their option to participate in the IRB-approved protocols for ovarian tissue banking through NPC.

How does CRBI membership with NPC benefit the patient?

For most patients, it will make absolutely no difference, because they will be able to use the more routine and effective options of embryo and oocyte banking. However, for our patients who choose ovarian tissue banking, we believe that our membership in NPC will provide our patients access to the best clinical practice available today.

Unlike embryo and egg banking, ovarian tissue banking for the purpose of fertility preservation is still highly experimental. In order to give our patient’s access to the most current banking methods and frontline research findings in this area, and therefore the best chance for benefiting from ovarian tissue banking, we decided to collaborate with the leaders in the field who are NIH-funded and most likely to produce the breakthroughs our patients need in the shortest time. Patients who wish to bank ovarian tissue can be enrolled in these ovarian tissue banking studies through the NPC under IRB 08-094. National Physicians Cooperative: Ovarian Tissue Cryopreservation as a Method of Fertility Preservation. In return for donating 20% of their ovarian tissue for research, (the remaining 80% is banked for the patient’s own use), some banking expenses are paid by the consortium. However, most costs will remain the patient’s responsibility if insurance will not cover the costs. Please call CRBI for additional information regarding this option.