Female Fertility and Cancer Treatment
The article may be useful for people born with ovaries and a uterus.
Fertility is the ability to get pregnant and have a child. When you are born, your ovaries hold hundreds of thousands of eggs. From the end of puberty until menopause, about 15-20 immature eggs (oocytes) are released each month. One of these will fully develop and become a mature oocyte. This mature oocyte is released into the fallopian tube. The egg is then either fertilized by sperm, which leads to pregnancy, or you will get your period (menstruate).
Over a lifetime, about 400 to 500 mature oocytes are released into the fallopian tubes. The undeveloped oocytes or the follicles needed to develop them can be damaged by cancer treatment. This can cause your period to change or stop. This can lead to infertility (being unable to get pregnant). Damage to the uterus or cervix by radiation or surgery can affect your ability to carry a pregnancy to term.
Chemotherapy and Fertility
Chemotherapy works by killing quickly-dividing cells. Many cells in our bodies divide quickly, like those lining the gut, hair follicles, and germ cells (including sperm and oocytes/eggs). Both cancerous and non-cancerous cells can be affected by chemotherapy. When these cells are damaged by chemotherapy, it causes side effects. These include diarrhea, mouth sores, hair loss, and being unable to have children (infertility).
There is no way of knowing who will become infertile with cancer treatment. The risk is based on:
- The medication(s) used: receiving more than one medication makes predicting fertility even harder.
- How long it is given for and what doses are given: higher doses and longer treatments increase the risk of fertility.
- Your age at the time you had chemotherapy: The older you are at the time of the treatment, the more likely it is that your periods will stop and/or you will become infertile.
- The size of the follicle pool (or the number of oocytes) before chemotherapy. Since this number lowers with age, the older you are, the higher your risk of infertility becomes because there are fewer oocytes to begin with.
Many studies look at when your menstrual cycle restarts as a predictor of fertility. Pregnancy cannot happen if your period doesn't return, but the return of periods does not always mean you can get pregnant. If you get your period back after therapy, you are also at risk of starting menopause earlier than those who did not have chemotherapy or radiation.
The group of chemotherapy agents called alkylating agents poses the greatest risk of causing infertility. These include:
Bevacizumab, a type of targeted therapy, has been found to cause ovarian failure that is sometimes permanent. Little is known about other targeted therapies. Thalidomide and lenalidomide are examples of medications that can cause birth defects, so you will be asked to use two forms of birth control while on these. Ask your provider about the possible risks for birth defects related to the medications you are receiving.
Treatments used to prepare for stem cell and bone marrow transplants are likely to cause infertility. Transplant regimens using busulfan and/or cyclophosphamide are more toxic to fertility than those using melphalan.
There is not enough research on newer medications to know how they will affect fertility. If you are getting or have received chemotherapy, it is important to speak to your provider about when it is safe for you to try to get pregnant. Each therapy can affect you differently, so it is important to talk openly with your provider about your plans for having children in the future.
Radiation Therapy and Fertility
The effect of radiation therapy on fertility depends on:
- The dose received.
- The part of the body treated.
- Your age at the time of treatment: As with chemotherapy, the size of the follicle pool before treatment is linked to the number of oocytes remaining after therapy. Younger people are more likely to have a larger pool and are less likely to enter permanent menopause at the time of therapy.
Younger people whose periods start again after radiation therapy are at risk of starting menopause earlier than those who did not have radiation or chemotherapy. Predicting when this menopause will happen is hard, putting pressure on younger people who wish to have a natural pregnancy. If you restart your period after treatment, you are not always able to get pregnant.
Total body irradiation (TBI) is used for stem cell and bone marrow transplants. The whole body gets radiation. TBI has a great effect on fertility, often leading to permanent ovarian failure. If you received TBI before puberty, you are more likely to get back ovarian function than those who received it after puberty.
Radiation therapy to the belly or pelvis can cause harm to the uterus and/or cervix. This can make it hard to carry a pregnancy to term. Radiation can also cause changes to the muscles, blood flow, and size of the uterus. This may keep an embryo from implanting. If you have received radiation to the uterus, you are at higher risk for miscarriage, preterm labor, and low birth weight babies. Despite these risks, the risk of birth defects is not increased, so long as radiation is not given during pregnancy.
The pituitary gland (in the brain) makes hormones (LH and FSH) that stimulate the ovary to make and release a mature female oocyte. Radiation therapy to the brain can harm the pituitary gland, affecting the ovulation cycle. This can lead to a shorter time for fertilization after ovulation. This can often be fixed by taking supplemental hormones.
Surgery and Fertility
Surgery that removes both ovaries or the uterus, cervix, and/or fallopian tubes will affect fertility. Depending on how advanced the cancer is, you may be eligible for fertility-preserving surgeries and should talk about these choices with your surgeon.
Hormone Therapy
Tamoxifen can temporarily stop or change menstruation, but this does not happen to everyone. It is possible to become pregnant while on tamoxifen. You should use two forms of birth control to prevent pregnancy. If you become pregnant while on tamoxifen, the medicine should be stopped right away due to the risk to the fetus. Also, tamoxifen can affect estradiol and FSH levels, making it hard to test ovarian function if you are taking this medicine (see assessment of ovarian function below).
Assessment of Ovarian Function after Therapy
The return of your period is not a good predictor of fertility. There are a few tests that can help check fertility. Follicle-stimulating hormone (FSH) and estradiol (E 2) are hormone levels that can be checked by a blood test on the 3rd day of menstruation. These levels are used to assess ovarian follicle reserve (number of eggs remaining in the ovary) and fertility.
These levels cannot predict exactly how many follicles are left or how long before infertility will start. One hormone, anti-Mullerian hormone (AMH), is made by early follicles and is a good predictor of the follicle reserve. Using ultrasound to count the number of antral follicles (those oocytes that are growing) on the 3rd day of the menstrual cycle can also be a good marker of follicle reserve. The number of follicles maturing is linked to the number that remains. While tamoxifen affects the levels of FSH and E2, it does not affect the antral follicle count, so this test may be useful in predicting future fertility if you are taking tamoxifen.
If I still ovulate, is there any danger or risk of becoming pregnant after therapy?
Studies have found no increase in birth defects in the children of cancer survivors, nor do these children have higher rates of cancer themselves (this does not apply to families with genetic cancer syndromes).
The DNA of oocytes can be harmed by cancer therapies, but this damage can repair itself in the months after treatment (the exact time needed for repair is unknown). Your provider may suggest that you wait a certain amount of time after treatment before trying to get pregnant. It is important to talk about your case with your provider. You may also want to talk with a fertility expert who works with cancer patients.
For breast cancer survivors, there has always been concern that pregnancy after treatment could increase the risk of recurrence, especially in estrogen receptor-positive tumors. However, studies have found that pregnancy does not appear to increase the risk of recurrence. It is not clear if getting pregnant after fertility preservation or using assisted reproductive technologies like IVF, intrauterine insemination (IUI), frozen embryo transfer, or egg/embryo freezing is safe for breast cancer survivors. It can be affected by the type of breast cancer, treatments received, and hormone receptor status.
You can also learn more about fertility preservation options and find links to resources for more information.