Female Fertility and Cancer Treatment | OncoLink Cancer Resources

How does cancer therapy effect fertility?

In a woman of reproductive age, one of the two ovaries begins to develop 15-20 immature eggs (oocytes) within follicles (cells which support its development) every month. Only one of these oocytes is permitted to fully develop and become a mature oocyte (the rest die), at which point it is released into the fallopian tube for possible fertilization in the uterus. A woman has a limited number of oocytes in her lifetime, with the highest number being present prior to birth (about 7 million at 7 months gestation). This number then slowly decreases from approximately 2 million at birth, to menopause, when approximately only 1,000 oocytes remain and stop maturing. Over a lifetime, approximately 400-500 mature oocytes are released into the fallopian tubes. If the immature oocytes stored within the ovary are damaged by cancer treatment, fertility is at risk. Damage can be to the undeveloped oocytes or to the follicles required to develop them. In addition, a woman needs to be able to carry a pregnancy to term. Damage to the uterus or cervix can compromise this ability.

It is important to understand that chemotherapy works by killing rapidly dividing cells. Chemotherapy is able to destroy large numbers of cancer cells because they are rapidly dividing and abnormally reproducing. Many other cells in our bodies are also constantly dividing, including those lining the gastrointestinal tract, hair follicles, and germ cells (including sperm and oocytes or eggs). Because these cells also become targets, we see side effects related to their destruction, such as diarrhea, mouth sores, hair loss, and infertility, respectively.

One other piece to the puzzle is the pituitary gland, located in the brain. This gland produces special hormones (LH and FSH), which in turn stimulate the ovary to develop and release a mature female oocyte. Radiation therapy to the brain can damage the pituitary gland, ultimately affecting the ovulation cycle, which may then result in a shorter luteal phase (days after ovulation during which fertilization occurs). This can usually be fixed with supplemental hormones.

Chemotherapy and fertility

Predicting the risk of infertility to each individual is often impossible. Risk is dependent on the drug(s) used, dosage received, duration of use, and the woman's age at the time of administration. Rarely does a person receive only one chemotherapy agent, and combining various agents makes predicting fertility a greater challenge. Higher doses and longer duration of treatment cause the highest risk of infertility. Older age at time of administration leads to a higher likelihood of infertility and amenorrhea (loss of menstruation). As age increases, smaller doses of chemotherapy are needed to result in infertility.

Fertility loss is also dependent on the size of the follicle pool (or number of oocytes) prior to chemotherapy. Given that this number decreases with age, the older the woman, the higher the risk of infertility becomes, because there are fewer oocytes at the outset. Unfortunately, there is no way to know for certain how many oocytes a woman has at any point in life, although some tests can estimate this number. Age can act as a guideline, but it is not an exact science. (See assessment of ovarian function below) For example, a study of amenorrhea in breast cancer survivors who received cyclophosphamide, methotrexate, and fluorouracil (CMF) found that 35-40% of women under age 40 did not regain menses, but as many as 80-95% of those over 40 did not. This means that somewhere between 5 and 20% of women over 40 DID regain menstruation, even though they were not expected to do so.

Many studies look at the resumption of the menstrual cycle as a predictor of fertility. Although pregnancy can not occur without resumption of menses, menstruation alone is not a guarantee of fertility. Some studies have reported pregnancy rates in survivors, but it is difficult to know how many were actually attempting to conceive. One must also consider other variables, including rates of intercourse, partner fertility issues, cancer therapies received, and time since therapy. Women who do regain menses after therapy are still at risk of entering menopause earlier than women who did not have chemotherapy or radiation.

With all of this in mind, we know that the group of chemotherapy agents called alkylating agents poses the greatest risk. These include cyclophosphamide, ifosfamide, BCNU, CCNU, chlorambucil, melphalan, and busulfan. Some agents known to have a low risk of infertility are vincristine, methotrexate, and fluorouracil (5-FU). There is not enough data on newer agents, including taxanes and targeted therapies, to address fertility after these agents. Therapies used in preparation for stem cell and bone marrow transplant are likely to cause infertility in women, although studies have found that pre-pubescent girls treated for childhood cancers have a good chance of regaining ovarian function. Transplant regimens utilizing busulfan and/or cyclophosphamide are more toxic to a woman's fertility than those utilizing melphalan.

Radiation Therapy and Fertility

Damage to fertility caused by radiation therapy is dependent on the dosage received, area of the body treated, and the woman's age at time of treatment. As with chemotherapy, the size of the follicle pool before treatment is directly related to the number of oocytes remaining after therapy. Younger women are more likely to have a larger pool and therefore are less likely to enter permanent menopause at the time of therapy. A dose of only 5 or 6 Gy can cause ovarian failure in a woman over 40, but larger doses (20Gy) are required to cause failure in women under 35. In women who received 20-30 Gy of radiation to the abdomen as children, 97% experienced ovarian failure or developed menopause earlier than normal (average age at menopause was 23 years in these survivors). As a reference, 50 Gy is typically recommended for the treatment of common gynecologic cancers.

Younger women who do regain menses after radiation therapy are not out of the woods. These women are at risk of entering menopause earlier than women who did not have radiation or chemotherapy. Predicting when this menopause will occur is difficult, putting pressure on younger women who wish to pursue a natural pregnancy. As with chemotherapy, women who resume menses have no guarantee of fertility.

Total body irradiation (TBI) is a technique used for preparation for stem cell and bone marrow transplants in which the entire body is irradiated. It is estimated that 85-90% of women who undergo TBI will have permanent ovarian failure, with only 10-14% regaining menses. Pregnancy rates in women who received TBI for transplant are reportedly around 2% (although as high as 12% in aplastic anemia survivors). Girls who have received TBI prior to puberty are more likely to regain ovarian function than those who received it post-puberty.

Radiation therapy to the abdomen or pelvis can cause damage to the uterus and/or cervix, leading to difficulty carrying a pregnancy to term. Studies have found that radiation can cause changes to the musculature, blood flow, and size of the uterus. This may prevent an embryo from implanting. Other complications that occur in higher rates in women who received radiation to the uterus include: miscarriage (38% vs. 12% in the general population), preterm labor (62% vs. 9%), and low birth weight babies (62% vs. 6%). Despite these risks, the risk of malformations of the fetus are not increased, so long as radiation is not given during pregnancy.

«Previous | 1 | 2 | 3 | 4 | 5 | 6 | Next »