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Fertility Preservation for Cancer Patients (Cryopreservation): FAQ
For any young person, a cancer diagnosis can be very traumatizing. Often, treatments that can be lifesaving can also be threatening to fertility. At the Johns Hopkins Fertility Center, we are available to counsel patients with a new cancer diagnosis regarding the risk their cancer treatments may pose to their fertility. Our policy is to see patients within one to two days of their cancer diagnosis as we understand the time-sensitive nature of their situation.
Below, our experts answer commonly asked questions about the impact specific treatments have on fertility and the fertility preservation options we offer, which include embryo, oocyte, ovarian tissue and embryo cryopreservation.
What is the risk of infertility after treatment with chemotherapy and/or radiation therapy?
Both chemotherapy and radiation therapy are toxic to the gonads: ovaries in females and testes in males. Females are born with a limited number of eggs, which are stored in the ovaries. In females, damage to the ovaries depletes this egg supply and results in premature ovarian insufficiency (premature ovarian failure or menopause). This can cause infertility and symptoms related to low estrogen levels, such as hot flashes, night sweats and mood changes. In males, damage to the testes is likely to result in diminished sperm production, but hormone production is less likely to be impaired. Therefore, sexual function may continue normally in spite of decreased or absent sperm production.
The effects of treatment depend on the specific chemotherapy used, the total dose and the age at the time of treatment.
What effect does age have on fertility after cancer treatment?
In general, the gonads of boys and girls are less sensitive to the effects of chemotherapy before the onset of puberty. Both boys and girls may go through a normal puberty and have normal reproductive function for a while, in spite of treatment during childhood or early adolescence. In girls, there is a risk of early menopause in the 20s or 30s. Radiation therapy to the pelvis or abdomen in boys or girls may cause enough damage to the gonads that puberty does not occur normally.
After puberty, sperm production is very sensitive to chemotherapy and radiation. Radiation to the pelvis or directly to the testicles will stop sperm production. Radiation to the upper leg or upper abdomen may cause some damage to the testicles, but sperm production may recover in these cases. Radiation therapy related to bone marrow transplantation usually causes infertility, but this has been reversible in a few cases, with recovery of sperm production up to seven years later.
In girls, the ovaries are very sensitive to chemotherapy and radiation after puberty and even more so as they get older. Women are born with all the eggs they will ever have. Women who are younger than 25 years old may have some eggs remaining after chemotherapy because their ovaries contain more eggs than older women. Even if their reproductive function seems to be intact after treatment (periods continue normally), they often have a risk of early menopause.
What are the effects of dose and type of chemotherapy on fertility?
Some types of chemotherapy are known to be particularly toxic to the gonads. Alkylating agents, for example Cytoxan (cyclophosphamide), is particularly damaging to both ovaries and testicles. Even low-dose Cytoxan given over a long period of time (e.g., for treatment of systemic lupus, rheumatoid arthritis or kidney disorders) can have a detrimental effect. Others, such as methotrexate, seem to be relatively safer. Current cancer treatment protocols often contain many medications given in overlapping or alternating regimens. Very little is known about the long-term effects of these newer regimens, but they are likely to cause damage to the gonads.
Is it safe to have a baby after cancer treatment?
First we must consider if there is an increased risk of birth defects, miscarriage or cancer in the offspring of people who have been treated for cancer. Second we will consider if it is safer to carry a baby after treatment for cancer.
Is there an increased risk of birth defects, miscarriage or stillbirths after treatment for cancer?
Treatment of cancer during pregnancy can pose a serious risk to the developing fetus. But for men and women who have completed their cancer treatment some time before pregnancy, there does not seem to be an increased risk of birth defects, miscarriages or stillbirths as a result of their treatment. Some cancers are known to run in families, and it is likely that the offspring of these cancer patients could be at increased risk of developing the cancer also. You should discuss your particular risk factor with your oncologist. Other than those cancers known to run in families, the risk of cancer in the offspring of cancer patients does not seem to be increased.
Is it safe to carry a baby after treatment for cancer?
Generally, yes. Women with cancers that are responsive to hormones, particularly breast and uterine cancer, may be an exception to this rule. Although breast cancer is believed to be stimulated by estrogen and there are high levels of estrogen in pregnancy, there is currently no evidence that pregnancy after breast cancer increases the risk of recurrence or spread. This is still a controversial area, and women with breast cancer should consider their options very carefully. Before considering pregnancy, it is advised women wait some years after cancer treatment to be certain the cancer is not one that will recur quickly. Women with early uterine cancers may still be candidates for pregnancy if the cancer can be controlled without a hysterectomy. Uterine cancer is responsive to estrogen but also inhibited by progesterone, and progesterone levels are extremely high in pregnancy.
Women who have had radiation to the pelvis or lower abdomen require special consideration with regard to pregnancy. If the uterus has been exposed to high doses of radiation, the endometrium (or inner lining of the uterus) may be destroyed. In this case, periods will have stopped and it will not be possible for the uterus to support a pregnancy. In addition, women who have had radiation to the uterus have a higher risk of miscarriage, early delivery, fetal growth restriction and other complications because the blood supply to the uterus is compromised and may not be able to increase as much as is necessary to support a pregnancy.
Women who have received high doses of adriamycin and/or radiation to the chest may also experience complications during pregnancy. In pregnancy, the heart has to work considerably harder to pump an increased volume of blood to the baby. If the heart muscle has been damaged, it may not be apparent until an increased stress (such as pregnancy) is placed on the heart and then heart failure can develop. Women who have had adriamycin treatment and/or radiation to the chest require careful evaluation by a cardiologist and careful follow-up in pregnancy to avoid serious complications.
Options for Women Before Treatment
Treatment for early cervical cancer or endometrial cancer generally includes hysterectomy. In a few select cases, this may not be necessary. In very early endometrial cancer, it is sometimes possible to treat the cancer hormonally without removing the uterus.
In very early cervical cancer, for example, removal of just the cervix (called trachelectomy) may be possible in order to retain childbearing potential.
If radiation to the pelvis is required, the ovaries can sometimes be moved out of the area expected to receive the most radiation. This procedure (called ovarian transposition) can at least partially protect the ovaries from the effects of radiation.
While ovarian cancer is frequently treated by hysterectomy and removal of both ovaries, early stages can sometimes be safely treated by removal of the affected ovary only.
These possibilities should be discussed with a gynecologic oncologist.
In-vitro fertilization followed by cryopreservation (freezing) of the fertilized eggs can provide an opportunity to have a pregnancy after treatment for cancer is completed. This procedure involves treatment with injectable fertility medications to stimulate development of multiple eggs. The eggs are retrieved in a procedure performed under anesthesia, called an oocyte retrieval, and fertilized with the partner’s (or donor) sperm and then frozen. The whole process generally requires two to four weeks.
IVF with cryopreservation of embryos has been used extensively for infertility treatment since the early 1980s and is considered a safe and routine procedure. The embryos can be stored for a number of years until cancer treatment is completed. Even if the cancer treatment results in ovarian failure, the woman can be given hormones to mimic a normal ovulation cycle and have the embryos transferred back to the uterus by a simple outpatient procedure. The chance of pregnancy is about 30 to 50 percent each time one to two embryos are returned to the hormonally prepared uterus (pregnancy rate is dependent on maternal age at the time the embryos were created). If several high grade embryos can be produced and stored, that should give the couple a reasonably good chance of achieving a pregnancy at a later date. Sometimes this is not possible because of the need to start cancer treatment quickly. An IVF cycle takes about two weeks to complete, and we can often start controlled ovarian hyperstimulation to harvest eggs on a random day during a woman’s cycle.
Cryopreservation of Unfertilized Eggs (Oocyte Cryopreservation)
Women who do not have a partner can still go through an IVF cycle and freeze unfertilized eggs. Unfortunately, freezing unfertilized eggs is still relatively new and has a much lower chance of pregnancy per frozen egg compared with a frozen embryo. Oocyte cryopreservation was considered experimental until 2013, when the experimental label was lifted due to a new method of freezing these eggs, vitrification, which increased oocyte survival. The current success rate is about 3 to 5 percent per egg, but recent research shows higher rates of pregnancy per egg are likely. This is an active area of research, and it is hoped that this success rate will improve in the future.
Cryopreservation of Ovarian Tissue
Ovarian tissue cryopreservation is an emerging option for fertility preservation. It involves harvesting ovarian tissue and freezing the tissue for future use. Harvesting this tissue does require a surgical procedure, usually a laparoscopy. One benefit of this option is it can be done immediately and therefore will not delay cancer treatment. It is also the only fertility preservation option available to prepubertal girls. A piece of ovary in a young woman contains thousands of eggs. Once cryopreserved, the ovarian tissue pieces can be transplanted back into the patient for future pregnancy. Because this is a new technique, it is considered experimental and is therefore generally not covered by insurance. To date, about 130 babies have been born after transplantation of cryopreserved ovarian tissue.
Medical Suppression of the Ovaries
Girls who have not yet gone through puberty are relatively protected from the effects of chemotherapy. However, even these girls can experience an early menopause years after the treatment has been completed.
Because girls who have not yet entered puberty are relatively protected from the effects of chemotherapy, it may be helpful to use a medication to inactivate or suppress the ovaries. This medication is called Depo-Lupron and is given as a monthly injection. It should be given at least 10 days before the start of chemotherapy to have maximum effect. This medication also has the effect of stopping menstrual periods. This can be useful because chemotherapy often lowers the platelet count, increasing the risk of heavy or prolonged bleeding during menstrual periods.
Options for Women After Treatment
What are the options for women after treatment?
It is important to assess the residual ovarian function after treatment for cancer. If the periods have stopped and especially if menopausal symptoms are present (e.g., hot flashes and night sweats), the ovaries have been damaged. Generally a blood test for FSH (follicle stimulating hormone) and estrogen will indicate whether the ovaries are still functioning. If the blood tests indicate the ovaries are not functioning, the ovaries may or may not recover. Sometimes periods start up again several months after the completion of treatment. Even irregular periods indicate the potential for conception. The challenge in the case of intermittent ovarian function is to identify the time of ovulation so that intercourse can be timed optimally. In this way, women who have had cancer treatment are like perimenopausal women. However, unlike perimenopausal women in their late 40s or 50s, cancer survivors with eggs still present in their bodies have a better potential for becoming pregnant. Monitoring ovarian function with blood test and ultrasounds is the best way to identify the time of ovulation.
For women in whom there seems to be no residual ovarian function, it is possible to get pregnant and carry a pregnancy using donated eggs (oocytes). In some cases, the donor is known to the recipient (such as a sister or friend), but more commonly, women use anonymous donors. The donor is treated with fertility drugs so that she will produce a large number of eggs. After egg retrieval, the eggs are fertilized with the recipient’s partner’s sperm. The fertilized eggs are placed into the uterus of the recipient after priming with hormones so that the uterus is prepared to accept the pregnancy. Most in-vitro fertilization programs have a donor oocyte program and accept patients up to the age of 50. The success rate using anonymous donors is about 50 percent per attempt.
Options for Men Before Treatment
The best way for men to preserve their reproductive potential at this point is to cryopreserve (freeze) and store sperm. In the past, this was not always a good option because many men with cancer have sperm counts that are less than normal. However, now with in-vitro fertilization and ICSI (intracytoplasmic sperm injection), even very small numbers of sperm can be used to establish a pregnancy.
In order to cryopreserve sperm, the man must be able to produce a semen sample, generally by masturbation. Fairly young men/teenagers should be able to produce a specimen suitable for cryopreservation, but in younger men, the subject can be difficult to bring up or discuss. The semen needs to be delivered promptly to a lab capable of freezing it properly. Ideally the semen sample would be collected right there in the lab. Most labs have a small private room available for this purpose.
If possible and if time permits, several semen specimens should be cryopreserved at intervals of two to three days. Most men can delay treatment for several days or a week for this purpose.
Shielding the Testicles from Radiation
If radiation to the pelvis is part of the treatment plan, a patient and his physician may want to discuss the possibility of shielding the testicles from radiation. Cure of the cancer is, of course, the most important consideration, so sometimes it will not be possible to shield the testicles and adequately treat the cancer.
In some experimental settings, pieces of testicular tissue from young boys have been cryopreserved in the hope that the tissue might produce sperm in a laboratory culture one day or that the tissue can somehow be returned to the testicle and function.