Causes of Female Infertility – Cancer

The impact of cancer on fertility depends not only on the type of cancer, with those affecting the reproductive organs likely to have a more detrimental effect on future fertility, but also on the treatment options selected and the age of the patient.

Dealing with a cancer diagnosis can be traumatic enough. There will be many factors to consider and decisions to make, all in a short time period. Maintaining close relationships with your spouse, your family and your friends is fundamental. One thing that may need to be considered when thinking about treatment options is fertility status and the likelihood of having or expanding a family in the future.

Chemotherapy

Chemotherapy works by killing cells in the body that divide quickly. The immature eggs (oocytes) in the ovaries tend to divide quickly, so are often affected by chemotherapy. Chemotherapy can cause temporary or permanent infertility when the drugs that are given, stop the ovaries from releasing eggs.

With temporary infertility, periods may become irregular or stop during treatment. It can take from 6 months to 2 years for the menstrual cycles to return to normal. Even if a woman is menstruating regularly after cancer treatment, she may still experience difficulties conceiving and may want to consult a specialist for advice.

The risk of permanent infertility depends on the female’s age, menstrual history, hormone levels and type of cancer; as well as the specific drugs she is given and how strong a dose she receives. With all these factors to consider, it can be difficult to predict if a woman is likely to be permanently infertile after chemotherapy. Women who are nearer to the menopause are more likely to experience permanent infertility, usually because their ovarian supply is already diminished. Chemotherapy can cause Primary Ovarian Insufficiency. It can also induce the menopause, with women typically experiencing it 5 to 10 years earlier than would normally be expected.

Chemotherapy can also cause a reduction in libido and reduced cervical secretions, making intercourse uncomfortable, difficult and/or painful.

Radiotherapy

Radiotherapy is a cancer treatment that uses high-energy rays to destroy cancer cells and shrink tumours. The impact of radiotherapy on fertility depends on the part of the body that is being treated. The types of radiotherapy that may affect fertility include:

• Radiotherapy to the pelvis. The pelvis is the lower part of the torso, located between the stomach and the legs. It contains the bladder and reproductive organs. If the ovaries or uterus are irradiated it will usually cause permanent infertility. The risk of infertility depends on the dose of radiation, age (the risk is higher the older you are), and if chemotherapy is combined with the radiotherapy. Targeting other organs in the pelvic area, also increases the risk of irreparable damage to the reproductive system. If the uterus is damaged by localised radiation, there is an increased risk of miscarriage during future pregnancies.
• Radiotherapy to the brain. This can also affect fertility if the pituitary gland is damaged. The pituitary gland normally releases gonadotropin hormones (LH and FSH), which stimulate the ovaries to release eggs. Damage to the gland can prevent normal egg release, meaning ovulation does not occur.
• Total body irradiation. This is usually given before bone marrow or stem cell transplant and will normally also cause permanent infertility.

Surgery

Surgery is used in cancer treatment to remove tumours and sometimes the surrounding tissues. It is fairly common for women with cancers of the uterus, fallopian tubes, ovaries, vagina and cervix to undergo surgery to remove the reproductive structures (hysterectomy, oophorectomy). Whilst this surgery can be lifesaving, it usually leads to complete infertility, which can be traumatic for younger women.

Where possible, for example, if the cancer is only affecting one ovary or fallopian tube, a surgeon may attempt ‘fertility conserving’ surgery. This would involve removing the affected ovary or fallopian tube, and leaving the other ovary, fallopian tube and the uterus. The remaining ovary will continue to function, releasing eggs and hormones, so there is still a chance of pregnancy.

A trachelectomy is a technique used to remove most of the cervix in cases of cervical cancer. Pregnancy is still possible, but the risk of miscarriage during subsequent pregnancies is increased.

The pituitary gland is vulnerable to damage following brain surgery. If there is a tumour in the surrounding area, the surgeon will usually endeavor to save the pituitary gland, but if damaged it will cause similar effects to those seen following radiation therapy.

Hormone Therapy

Some cancers are stimulated by, and grow rapidly in the presence of hormones. This is particularly common in some breast cancer cases, such as those that are oestrogen receptor positive (ER positive). When this happens, doctors will often prescribe drugs to reduce or suppress hormone production, examples include Goserelin and Tamoxifen. These drugs often cause periods to stop or become irregular. They also cause menopausal symptoms, such as hot flushes, difficulty sleeping, vaginal dryness and mood fluctuations.

Falling pregnant during hormone therapy is unlikely, but not impossible. As the drugs can be harmful to developing babies, it is recommended that additional contraception is used for the duration of the treatment. Unless the patient goes through the natural menopause whilst undergoing treatment, normal fertility is usually restored once drug treatment ceases. However, the duration of hormone therapy treatment may interfere with childbearing, as some women need to take hormone therapy drugs for up to 10 years.

Preserving fertility

In terms of cancer, even if the recommended treatment options are likely to cause infertility, there are options available to try and preserve fertility, including:

• Freezing embryos for In Vitro Fertilisation (IVF).
• Freezing eggs.
• Freezing ovarian tissue.

These must be done before starting treatment.

With IVF a woman gets fertility drugs to stimulate her ovaries to produce eggs. The doctors then collect the eggs and fertilise them using sperm (either belonging to her husband/partner or a donor) in a laboratory, creating embryos. The embryos are frozen until required, at which point they are transferred to the womb to grow and develop. It is a complicated process and does not always succeed.

Women can also freeze their unfertilised eggs if they do not currently have a partner, but this has a lower pregnancy rate than IVF.

Freezing ovarian tissue is another option. This involves removing ovarian tissue and freezing it before chemotherapy starts. The theory is that, once treatment is complete, the stored ovarian tissue can be transplanted back into the female’s body, restoring fertility. Freezing ovarian tissue is a relatively novel procedure that still requires optimisation.

In the case of radiotherapy to the pelvic area, it may be possible to move the ovaries out of the treatment area before radiotherapy begins. This is called ovarian transposition. Ovarian transposition can be used to prevent an early menopause and is one way of maintaining the viability of the ovarian eggs so that pregnancy after radiotherapy is possible.

These techniques are not always successful in preserving fertility, but can provide relief and hope at a time when it is most needed.