Royal College of Physicians
Royal College of Radiologists
Royal College of Obstetricians and Gynaecologists
The Summary and Recommendations of this report are set out below. The complete report is available as a pdf:
Summary
Male and female gonadal toxicity are common complications of modern anti-cancer treatments. Although effective cancer therapy, and where possible cure, are of paramount importance, infertility and hypogonadism can be a source of considerable distress. The gonadotoxic effects of radiotherapy and the older chemotherapy regimens are well described. However, a profusion of new drugs and antibodies are now in routine use with poorly validated gonadal toxic effects.
It should be noted that chemotherapy drugs are also used in some non-malignant diseases. The comments in this report also apply to this group.
All patients with reproductive potential requiring anti-cancer treatment should be fully informed prior to treatment about the possible gonadal toxic consequences of any given treatment approach, and this discussion should be documented. These discussions should take place in private, should involve appropriate family or other individuals, and whenever possible should be conducted by experienced, preferably trained, staff.
Spermatogenesis is highly sensitive to the effects of chemotherapy and irradiation and male patients should, where relevant, routinely be offered sperm banking before treatment starts. Where sperm are absent from the ejaculate, testicular sperm extraction can sometimes be successful.
Testosterone deficiency in males is a less common complication of treatment but easily correctable with testosterone replacement.
The ovary is also sensitive to cancer treatments. When there is a possibility of gonadal damage, methods of preserving fertility should be discussed.
Where there is a partner and sufficient time, embryos can often be successfully generated and stored using in vitro fertilisation (IVF) techniques. Egg and ovarian tissue storage are also technically feasible; however, very few successful pregnancies have been reported. The latter techniques are not currently widely available and it is recommended that a service should be developed in the context of research studies.
Uterine function can be particularly damaged by irradiation and the late effects of this treatment may affect subsequent pregnancy.
Premature menopause is a common complication of anti-cancer treatment and, depending on the context, should be treated with hormone replacement.
This document seeks to describe the patient population who are at risk and current concepts in the preemptive management and management of gonadal toxicity. We also discuss developments that are likely in the next five to ten years.
Recommendations
- All patients with reproductive potential who require anti-cancer treatment either for cancer treatment or benign indications should be fully informed about potential gonadotoxic side effects at the time of diagnosis and prior to potentially gonadotoxic treatment. Alternative treatment strategies causing less gonadal damage should be discussed where relevant.
- Discussion and advice given about gonadal toxicity should be carefully documented in the patient’s notes. Written information should be provided about contraception, gonadal damage and techniques to preserve fertility. Specialist psychological support and counselling should be available to all these patients.
- Sperm banking must be considered for all males prior to treatment that carries a risk of long-term gonadal damage. Testicular sperm extraction is sometimes possible even when azoospermia is present. This technique is not currently widely funded.
- All females should be fully informed at diagnosis of the potential for gonadal or uterine damage caused by anti-cancer treatment, together with the possibility of early menopause.
- Embryo storage prior to treatment is possible for the minority of patients with a partner and sufficient time for IVF.
- Egg and ovarian storage are techniques in development which are not currently funded by the National Health Service. Very few live births have been reported after either technique worldwide. It is, however, anticipated that the results will improve. It is recommended that a researchbased egg and ovarian tissue storage facility be developed at a number of collaborating sites in the UK, which should be available for younger female patients likely to be sterilised by their cancer treatment.
- The literature in the field of gonadal toxicity is very limited, with few or no randomised trials. It is imperative that a research base/evidence base be developed in this field. Clinicians are encouraged to seek funding and research bodies to support further studies in this area. In particular the gonadal effects of new anti-cancer agents are very poorly validated.
- In 2004 the National Institute for Health and Clinical Excellence (NICE) issued a report, Fertility: assessment and treatment for people with fertility problems, which considered cryopreservation of gametes and embryos in patients undergoing gonadotoxic treatment. Universal access to sperm, egg and embryo storage was recommended. There is, however, currently no national policy for funding any of the techniques which aim to preserve fertility or treat the effects of gonadal damage, demand for which will always be very limited. The Working Party strongly recommends that an agreed national policy and funded nationwide equity of access to resources be available. Furthermore, we recommend an ongoing audit of the implementation of this recommendation.
- 9 Provision of sex hormone replacement, where required, should be brought into line with other long-term replacement therapies and be exempt from prescription charges.
Recommendations on funding
NHS funding bodies are strongly encouraged to develop equitable funding protocols for patients in this field, if necessary with national guidance. Access to fertility services is often urgently required when there is a need to proceed quickly with treatment for threatening cancer. The Working Party makes the following recommendations.
- Long-term sperm banking should be universally available and fully funded. This is a routine evidence-based technique and should be available at short notice to all males commencing treatment which carries any risk of future infertility.
- Testicular sperm extraction is an established technique for obtaining sperm for IVF in patients who are azoospermic either before or after treatment with chemotherapy. The Working Party recommends that this procedure be available nationwide to appropriately selected males.
- A small minority of females with cancer who require chemotherapy or irradiation likely to cause infertility are suitable for emergency IVF (implying egg harvesting and IVF using a partner’s sperm). It is strongly recommended that this service be provided at short notice for appropriate female patients likely to be sterilised by their treatment. It is accepted that this may give patients with cancer precedence over those seeking treatment for infertility in other circumstances.
- Egg and ovarian tissue storage techniques should currently be regarded as developmental. These are not at present widely available with NHS funding but are often provided in the private sector. National funding bodies (Cancer Research UK, the Medical Research Council and Department of Health) are strongly encouraged to fund development of a small network of research-based centres providing universal access to and further development of these techniques. It is anticipated that the technology in this field will rapidly improve in the next few years. An evidence-based approach to the management of the small minority of patients requiring these techniques is essential.
- There is no routine NHS provision for manipulation of stored gametes or embryos once cancer treatment has been completed. This is regarded as inappropriate and routine funding streams should be available for these patients.
- Male and female hormone replacement treatments are currently not exempt from prescription charges. This is anomalous given the national funding arrangements for other endocrine replacement treatments. It is recommended that these treatments be exempt from prescription charges.
- Psychosocial support independent of treating clinicians should be routinely available and funded for all patients described in this report.