INTRODUCTION

Each year, cancer is estimated to occur in 113 per 100,000 women under age 50 in the United States. Treatment of cancer has improved dramatically over the past several years, and it is estimated that 77% of patients under 45 survive at least 5 years. The trend toward delaying childbearing means that many patients will not have had children when they are diagnosed. While there is recognition that cancer therapy can affect a patient’s fertility, less than 25% of oncologists inform their patients about their risks and options.

Chemotherapy or radiation therapy for malignant and nonmalignant diseases often results in premature ovarian failure and infertility. Examples of chemotherapy that may lead to infertility are listed in Table 1. Diseases that require chemotherapy, surgery or radiation and may cause infertility are listed in Table 2. Affected individuals, even children, can sometimes benefit from fertility preservation technologies. Such techniques can also be utilized when there is risk of damage to the ovarian reserve due to ovarian surgery.

METHODS TO PRESERVE FERTILITY IN WOMEN

Fertility preservation requires individualization. The optimal approach depends upon the type of cancer treatment (radiation versus chemotherapy), time available, patient's age, type of cancer, and whether the patient has a partner. Male cancer patients have long been able to preserve their fertility by freezing their sperm. Tour de France champion Lance Armstrong's three children were conceived with sperm he banked before chemotherapy.

Options for women have developed more slowly. In vitro fertilization and embryo freezing is a well-tested procedure that leads to high pregnancy rates (30-40% per frozen embryo). Hormonal stimulation is required, and may not be recommended for certain types of cancer. This also requires that the woman has a partner, or be mature enough to pick a sperm donor. If the patient doesn’t survive her cancer, than embryos are left behind.

Oocyte Freezing. Harvesting and freezing mature eggs, which later can be fertilized, avoids the problem of a patient having to have a partner or pick a sperm donor, and prevents “orphan” embryos. The first baby from a frozen egg was born in 1986, and there have since been more than 550 such babies worldwide. The first American baby conceived using frozen sperm and a frozen egg was born last year.

Freezing eggs is more complicated than freezing sperm or embryos: The water inside the egg can form ice crystals, which can damage the egg and its chromosomes. Depending on the age of the woman, as many as 15 or 20 eggs can be retrieved from the ovary after stimulation with fertility drugs. Pregnancy rates range from 3-5% per frozen egg, while 22 percent of the embryos developed from a frozen egg will result in a pregnancy.

Because the birth rate with frozen eggs is so low, the American Society for Reproductive Medicine considers the technology experimental. Still, it says it may be appropriate for cancer patients who have no viable alternative, as long as they are informed about the potential risks of fertility drugs and egg retrieval, the costs and the low success rates.

Oocyte donation. For the patient who cannot freeze eggs or embryos, an egg donor may be a viable option. Pregnancy rates with donor eggs that can be fertilized and transferred to the patient’s uterus are very high as long as the patient has a healthy uterus (50-60%).

Ovarian Tissue Freezing. There are no large randomized clinical trials to evaluate the interventions described above, and there are no long-term follow-up studies assessing the possible impact of fertility treatment on cancer survivors. For these reasons, many oncologists do not support the use of assisted reproductive technology (ART), which involves ovulation induction and high estrogen levels, in women with estrogen-dependent malignancies. For these women, ovarian tissue freezing may be an option. This does not require hormonal stimulation and may be used for pre-pubertal patients. Hundreds of thousands of immature eggs may be preserved this way, but extensive laboratory culture or surgery to replace the ovarian tissue (auto-grafting) is necessary. Auto-grafting has resulted in several pregnancies, but the technique is still in early development.

Patient concerns. One of the strongest predictors of emotional well being in cancer survivors, besides sexual function, appearance, and employability, is feeling healthy enough to be a good parent. Cancer survivors are often fearful that their history of cancer or its treatment will have an adverse impact on their offspring by placing them at risk for malignancy, congenital anomalies, or impaired growth and development. They are also concerned about the risks of cancer recurrence, infertility, miscarriage, and achieving a successful pregnancy outcome.

Despite these concerns, surveys have reported that fewer than 60 percent of respondents had received information about fertility after cancer treatment, and even fewer had received information about potential risks to offspring, according to Fertile Hope, a New York based non-profit group that provides information and support for cancer patients.

To date, research suggests that pregnancy after cancer does not trigger recurrence, even after breast cancer. While chemotherapy can damage growing eggs and sperm, and potentially increase miscarriage risk, this damage generally resolves within 6 months to 2 years. Pregnancy after cancer can have some increased risks, such as heart damage after certain types of chemotherapy, so careful monitoring during pregnancy is important.

Birth defect rates of children born to cancer survivors are noted to be no higher that the general public (2-3%), and no unusual risk for genetic diseases (Down syndrome, Turner syndrome) has been identified in the offspring of cancer survivors. While there are genetic cancer syndromes that may increase the risk of a specific cancer in offspring of cancer survivors, no unusual cancer risk has been identified in these children. Patients with inheritable diseases can have treatment with in vitro fertilization and preimplantation genetic diagnosis to select unaffected embryos for implantation (Table 3).