Cancer in children and future reproduction

In 2010, approximately 10,500 boys and girls in the US and 160,000 worldwide are expected to be diagnosed with cancer before the age of 15. In addition hundreds of thousands of adolescents are treated for cancer yearly between the ages of 15 to 19.

Getting beyond cancer treatment involves a focus on wellness and ways to improve quality of life. Discover ways to maintain a healthy lifestyle, signs to look for, potential risks and ways to celebrate the life of a child with cancer.

The specific type of cancer varies with age and geographical distribution.  In the US the most common (American Cancer Society)  are                  Leukemias (31%)
Brain and nervous system (21.3%)
Neuroblastoma (7.1%)
Wilm’s tumor (5.2%)
Non-Hodgkin Lymphoma (4.3%)
Rhabdomyosarcoma (3.3%)
Retinoblastoma (2.6%)
Osteosarcoma (2.5%)
Ewing sarcoma (1.6%)
Others e.g ovarian germ cell tumors, Hodgkin lymphoma, liver cancer

With improvement in survival (80% in the US), Current priorities for childhood cancer management aim at improvement of quality of life of the growing number of childhood cancer survivors. Specific to reproduction, preservation of fertility aims at enabling children and adolescents to make reproductive choices that cannot be delayed till they reach maturity.

Effect of treatment of childhood cancer on fertility. It is very important for children and their families are informed about the effects of cancer treatment before shortly after diagnosis and certainly before they start treatment.

Children treated for childhood cancer are at risk for delay or failure of puberty. They are less likely to be biological parents in adulthood. Two large studies (The Childhood Survival Study in the US and The Norwegian Radium Hospital study) indicated that children treated for cancer are 50% less likely to become parents when compared to those not exposed to cancer treatment. Modern cancer treatment include surgery, multi-drug chemotherapy, radiation, biological agents and sometimes hematopoietic stem cell transplantation (bone marrow transplantation). Some cancers especially in boys can impair fertility independent of treatment e.g Hodgkin lymphoma and testicular cancer.

Chemotherapy especially alkylating agents cause accelerated loss of germ cells (oocytes or sperm producing cells).

Radiation of the ovary or testes can lead to partial or complete loss of germ cells depending on the total dose and fraction used. Also radiation of the head can affect hormone production from the master gland in the brain and impair ovulation or sperm production.

Bone marrow transplantation requires pre-treatment with high dose chemotherapy and total body radiation and is associated with loss of fertility in the vast majority of boys and girls.

Surgery to remove the ovary or testes is sometimes required  for cancer treatment e.g. germ cell tumors of the ovary or testes.

Methods of fertility preservation in girls. Modification of treatment plan is sometimes possible to prevent damage to reproductive tissue. For example, girls diagnosed with germ cell tumors of the ovary, its possible to preserve one ovary and the uterus. Freezing of ovarian tissue or eggs are available options for preservation of fertility in girls. After puberty, ovarian stimulation is possible, followed by egg retrieval and freezing. This require about 2 to 3 weeks to accomplish. This method require ovarian stimulation.  Estrogen produced during stimulation may lead to advancement of secondary sex characters e.g. breast development. Ovarian tissue freezing is possible for girls before and after puberty. It can be performed in one day and does not delay cancer treatment. It is considered when cancer treatment is expected to be associated with very high risk for ovarian failure. One ovary is harvested using minimally access surgery. Visible follicles in the ovary are aspirated using a needle and any eggs obtained are frozen. The ovary is the cut into thin slices and frozen. The ovary can be transplanted later for the purpose of initiation of puberty and reproduction. Unfortunately, transplantation is not suitable for certain cancers that carry high risk for contaminating the graft e.g. leukemias.

Methods of fertility preservation in boys. The standard for fertility preservation in men is sperm freezing. In boys, ethical and physical consideration issues may interfere with sperm collection from young boys. In studies done two decades ago, most boys start to emit sperms at ages 9 to 11 years, even in the absence of pubic hair. Practically this can be assisted by a vibratory stimulation device. Sometimes, for social or religious reasons its difficult to ask young boys to produce sperm samples. The other available option is a simple surgical procedure to retrieve sperm from the testes, testicular sperm aspiration or extraction (TESE). Tissue from the testes is then frozen for later use at maturity, using ICSI (direct injection of sperm into an egg). There are options for young boys e.g. testicular stem cell freezing, but they are experimental and not ready for general use.

Genetic issues and preservation of fertility in children. Some children develop cancer because they carry a faulty gene e.g. retinoblastoma. Children can be tested for this gene. If the abnormal gene is detected, embryos or eggs produced by these children can also be tested – preimplantation genetic diagnosis (PGD) and only healthy ones are used. This will prevent the gene from being transferred to their future children.

Ethical considerations. Fertility preservation in children is a complicated issue for parents and children alike. Ethicist advised that fertility preservation procedures should be offered to children when there is high risk for loss of fertility. If the proposed method entails delay in cancer treatment, this delay should not affect treatment outcome. Informed consent should be obtained from parents and ASSENT should be obtained from the child. Minors who are sufficiently mature to achieve a developmentally appropriate awareness of their condition and the risks and benefits of the available treatment alternatives should give their approval to the use of such treatment. Every measure should be taken to assure that the child will control the fate of sperm, eggs or reproductive tissue when they reach maturity. Nobody will have custody over reproductive cells or tissue except the person who produced them.

Recent psychological research from UK indicated that (Crawshaw & Sloper 2010)

For some young men and women treated for childhood cancer, fertility concerns dominates cancer legacy. Professional and social networks provided few opportunities to ask questions, receive information, process feelings or develop handling strategies. Beliefs about the extent of fertility damage did not necessarily relate to information received. For some, fertility matters affected identity, well-being and life planning as well as reproductive function. This was not restricted to particular ages, life stages, gender or time since treatment ended and was heightened by associated stigma and silence. Opportunities for dialogue should be offered regularly across health and social work disciplines given fertility’s psychological and social as well as medical significance.

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