by: Aimee Seungdamrong M.D. Director of Fertility Preservation University Reproductive Associates
At University Reproductive Associates, we work closely with oncologists to offer patients, who have been recently diagnosed with cancer, information about the ways cancer therapy may alter their fertility. We counsel them about their options for fertility preservation prior to cancer therapy as well as childbearing afterwards.
These days, more people are surviving cancer due to earlier diagnosis and better cancer therapies. The healthier cancer survivors are, the more likely they are to be able to consider starting or growing their families after treatment. Another improvement in cancer therapy is that many cancer treatments used today are less damaging to one’s fertility. However, for some women, the best treatment for their malignancy involves chemotherapy, radiation therapy, or surgery that will permanently damage their reproductive systems. In addition, many women with a cancer diagnosis will be asked to wait several years after treatment before they are deemed healthy enough and disease free long enough by their oncologists to be able to carry a pregnancy. In these instances, cancer patients and survivors often worry that menopause or decreased fertility may occur before they are ready to become pregnant.
The primary concern after completing chemotherapy or radiation is whether the ovaries and uterus are working enough to achieve and carry a pregnancy. Achieving pregnancy naturally requires fertilization of an egg from a functioning ovary by a single sperm after which the resulting embryo develops in the uterus until delivery. Chemotherapy may damage the ovaries and eggs resulting in permanent loss of the eggs and premature infertility or menopause. Once eggs are destroyed, the ovaries cannot make new ones. Radiation therapy to the pelvis can alter the uterus making it much more difficult or even impossible to implant an embryo or carry a pregnancy to full term. Surgical management of some uterine, cervical, or ovarian cancers requires removal of the uterus and/or ovaries resulting in sterility. In males, chemotherapy, radiation therapy, or surgery can damage sperm production.
Before cancer treatment begins, there are several options for preserving fertility. The most effective technique for fertility preservation is freezing embryos. This is achieved by growing several eggs in a woman’s ovaries during a one to two week course of injectable fertility medications. The eggs are removed from the ovaries during a procedure under anesthesia called an oocyte (egg) retrieval. The eggs are then fertilized with in a laboratory with her male partner’s sperm (or donor sperm) to form embryos that are cryopreserved (frozen) for future use. This process is known as in-vitro fertilization, or IVF.
For women without a male partner, the eggs can be frozen without being fertilized. This process is known as oocyte cryopreservation. When a woman is deemed healthy enough by her oncologist to proceed with a pregnancy, the eggs are thawed and fertilized with her partner’s sperm or a donor’s sperm. The resulting embryos are implanted in her uterus to achieve pregnancy.
Both embryo freezing and egg freezing are standard of care options for fertility preservation prior to cancer treatments. The pregnancy rates vary depending on the health of the eggs and embryos. In general, the older a woman is at the time of embryo or egg freezing, the less successful it is. However, the age at which a woman undergoes the embryo transfer and implantation does not impact pregnancy chances. Other general health concerns and problems with the uterine cavity can decrease the chance of implantation and these problems can be more frequent as a woman’s age increases.
An experimental option that avoids high doses of medications and high levels of estrogen is in-vitro maturation (IVM). Immature eggs are obtained from the ovary, matured in the laboratory, and are then frozen. Few medications are required for IVM and thus the estrogen levels remain low. Pregnancy rates are not as high with IVM as compared to growing the eggs in the ovary and then utilizing embryo freezing or oocyte freezing. Therefore this is an option that is possible but not often utilized.
Ovarian tissue freezing is another experimental option that is available prior to systemic chemotherapy or radiation to the pelvis. One or both ovaries are removed from a woman and frozen in small strips. When the woman is healthy enough to attempt pregnancy, these strips of ovarian tissue are re-implanted in her body in a second surgical procedure and can then recover the ability to produce eggs. More than twenty babies have been born worldwide through this therapy. While this is an encouraging option, it is very much still in the experimental phase. In comparison, hundreds of thousands of children have been born after in-vitro fertilization and oocyte cryopreservation. Furthermore, this procedure may not be appropriate for patients with leukemia as the ovarian tissue may contain cancerous cells that can resume growth in the bloodstream. This also may not be appropriate for BRCA gene mutation carriers due to their increased lifetime risk of ovarian cancer. Studies are currently being conducted to develop other ways of obtaining eggs from ovarian tissue without the need for re-implantation.
If a woman has not yet undergone chemotherapy and/or radiation treatment, these techniques are available in addition to other fertility conserving methods. Other options including shielding the ovary from radiation and surgically moving the ovaries out of the pelvic radiation field, both of which may decrease the risk of ovarian damage. Unfortunately, systemic chemotherapy does not allow for selective protection of the ovaries.
Barriers to fertility preservation with egg and embryo freezing are 1) the ovarian stimulation with fertility medications which is required for growth of the eggs and 2) the length of time required to obtain eggs (2-3 weeks), and 3) financial considerations. Firstly, during the ovarian stimulation, estrogen levels can rise to 2-10 times that of their natural levels. This is a concern because some women have estrogen sensitive tumors, such as breast or uterine cancer. To combat this risk, we use estrogen-lowering medications in conjunction with fertility medications during ovarian stimulation, which allow growth of eggs but decreased circulating estrogen levels during the cycle. Furthermore, women with these malignancies will need clearance from their oncologist prior to undergoing a fertility preservation procedure and prior to attempting pregnancy. Secondly, the time required to grow eggs and freeze them is sometimes a barrier to fertility preservation that we cannot surmount. Some patients who require immediate chemotherapy or surgery must forgo a fertility preservation procedure because we simply do not have the time to complete the process or procedure of fertility preservation. Lastly, the financial costs of completing an oocyte or embryo cryopreservation procedure are often not covered by standard health insurance and can range in the many thousands of dollars. We work closely with survivorship groups and pharmaceutical companies to offer patients deep cost savings in order to complete their fertility preservation procedures.
Women who have been recently diagnosed with cancer have a great many decisions to make regarding their health and fertility. By the time they have reached our consultation, they have been given a diagnosis that most of them never expected and which they must adjust to emotionally. They have completed several time sensitive diagnostic tests, some of which have required surgeries or biopsies. They have spent time trying to understand their diagnosis and decide which cancer therapies to complete and they have begun to adjust their lives and work schedules and families to arrange for support. At this point, we are here to help them understand the implications of all of their recommended treatments on their fertility and possibilities of growing a family. Some women are at the beginning of their reproductive lives and have not truly begun to think of childbearing. Some have been considering reproduction already but have not been successful and the diagnosis of fertility damaging cancer therapy is another setback that they didn’t expect. Others have already begun their families but would like the option of another child. Others are not sure if they would like to have children but would like to make the most informed choice that they can. For all women, it is important that we provide as much useful information as possible so that each can make a choice about her fertility that will be important for the rest of their life. Each woman and family will choose differently for different reasons. Some will proceed to a fertility preservation procedure. Some will not. There are no wrong choices as long as the choices are informed, with all of the necessary facts provided and questions answered.
After cancer treatment has been completed and a woman is allowed to consider pregnancy, the first step to building or growing her family is to evaluate her ovarian and uterine function. A hormonal evaluation can be done to determine if the ovaries are functioning and if eggs are likely to be available. If the ovaries have healthy eggs and the uterus is normal, without other barriers to conception, pregnancy can often be achieved without assistance.
However, if a woman’s ovaries are not working well enough to conceive, we then turn to the preserved eggs or embryos. If embryos have been preserved, the uterus is checked and prepared and the embryos are implanted. If oocytes have been preserved, they are thawed, fertilized, and then implanted into a normal and prepared uterus.
If fertility preservation has not been completed, there are other options to growing or starting a family. Eggs can be donated from a family member, friend, or found through an anonymous egg donation center. Eggs donated from an anonymous person are widely available and commonly used. Anonymous egg donors are often healthy young women who are rigorously screened for their health and fertility and who donate eggs after undergoing ovarian stimulation with injectable medications similar to the stimulation performed for an IVF procedure. The donated eggs are fertilized with her partner’s sperm or donor sperm to achieve pregnancy. With this technique, women with premature menopause but a functioning uterus are able to carry a pregnancy.
The uterus is an important part of childbearing. Women who have lost the ability to carry a pregnancy due to pelvic radiation, hysterectomy, or other condition affecting uterine health have the option of using a gestational carrier. A gestational carrier is a woman who will carry a pregnancy conceived using one’s own embryo or an embryo fertilized from a donor egg. Gestational carriers may be used at any time after embryos are cryopreserved. Some families have opted to use gestational carriers in the time after cancer therapy is completed but before a woman is allowed to carry a pregnancy herself. Adoption is also available for those who are unable to or choose not to utilize any of the above therapies prior to cancer treatment.
For males with a cancer diagnosis, treatment with chemotherapy and radiation may affect sperm counts and quality. For men who have yet to receive cancer treatment, sperm can be frozen for future use after ejaculation or by surgical sperm retrieval. In-vitro fertilization techniques allow for fertilization of an egg from a single sperm. Because of this, sperm from just one ejaculate or from a surgical retrieval may be enough for several IVF cycles. Lastly, in cases where sperm production has declined substantially, donor sperm, which is widely available, can be utilized with either natural conception techniques or with in-vitro fertilization.
In conclusion, fertility preservation options prior to cancer therapy as well as family building options after cancer therapy are available to both women and men. There are many considerations to be taken into account including the medical, emotional, financial, and practical aspects of making an informed and important choice about fertility. We applaud the oncology community for in the great advances they have made in saving thousands of lives touched by cancer. We hope to help as many patients as we can enjoy the benefits of their life-saving therapy including the possibility of having children.
