Introduction
1-2% of cases of invasive cancer occur during reproductive age (between 25 and 39 years) (1).
Many forms of systemic anti-cancer therapy (SACT) involve the use of radiotherapy or chemotherapy agents that are associated with significant gonadal toxicity (2). Subsequent loss of fertility may negatively impact quality of life in cancer survivors (3).
Despite this, a number of barriers exist that may prevent cancer patients from receiving fertility preserving treatments (FPT), including concerns about potential delays to initiate SACT, or a lack of knowledge regarding fertility preservation treatments or the availability of local centres able to provide these (4).
The purpose of this document is to provide health care professionals within the Wessex region with an overview regarding the SACT regimens associated with loss of fertility and the FPT options available to cancer patients; as well as practical information regarding the process of making referrals for these treatments.
The potential effects of SACT agents known to be associated with infertility are summarised below. Meanwhile, the impact of newer immunotherapy and small molecule inhibitor therapies on fertility are yet to be established. (5)
Anti-Cancer Treatments Associated with Infertility
Males
Radiotherapy
Radiation therapies begin to affect spermatogenesis gradually from 0.1 to 1.2 Gy; however, the dose limits at which azoospermia becomes permanent remain unclear.
Chemotherapy
The table below shows selected chemotherapy agents known to affect spermatogenesis.
Anti-Cancer Treatments Associated with Infertility
Females
Radiotherapy & Chemotherapy
The table below shows selected SACT and radiotherapy regimens associated with a risk of fertility in females
Fertility Preserving Treatments
Males
In post-pubertal males, the established approach to fertility preservation is the cryopreservation of ejaculated sperm.
Females
The table below displays selected FPT for female patients.
Referral Pathways and Funding
Males
Referrals for sperm cryopreservation should be made to Complete Fertility Centre Southampton (CFCS), based at the Princess Anne hospital in Southampton. This service is NHS funded for oncology patients.
Referrals can be made by sending a completed referral form to labcompletefertility@uhs.nhs.uk. The referring clinician should also telephone the unit on 02380 010 570, choosing option 3 for the laboratory, to confirm receipt.
Prior to sperm collection, CFCS require that the patient has been screened for HIV and hepatitis B and C.
Females
Referrals may either be made for oocyte cryopreservation to CFCS or ovarian tissue cryopreservation to Future Fertility Programme Oxford (FFPO).
Complete Fertility Centre Southampton
Oocyte cryopreservation is offered by CFCS and is NHS funded for oncology patients. However, not all patients will be eligible for NHS-funded treatment (for example, based on their location or residency status). Eligibility status is checked and funding applications are made by the team at CFCS.
Referrals can be made by sending a completed referral form to Dr. M. Saran via uhs.completefertility@nhs.net. The referring clinician should also telephone the unit on 02380 010 570, choosing option 3 for the laboratory, to confirm receipt.
Prior to oocyte storage, CFCS require that the patient has been screened for HIV and hepatitis B and C.
Future Fertility Programme Oxford
FFPO offer ovarian tissue cryopreservation only. This treatment is funded through charitable funds.
FFPO request that the referring clinician performs the following blood tests prior to referral of a patient:
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Follicle stimulating hormone (FSH)
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Lutenising hormone (LH)
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Anti-Mullerian hormone (AMH)
Referral forms and eligibility criteria are under version control, and therefore FFPO mandate that the latest forms are requested at the time of referral by emailing
orh-tr.futurefertilitytrust@nhs.net or calling 01865 220076 (24 hour answerphone)
Referrals should be made by sending the following documents to
orh-tr.futurefertilitytrust@nhs.net:
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Completed referral form
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Relevant pathology reports and clinic letters
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Results of hormonal blood tests (above)
References
[1] Melo, A. S., Paula, C., Rufato, M., Rufato, M., Rodrigues, J. K., Ferriani, R. A., & Barreto, J. (2019). Fertility optimization in women with cancer: from preservation to contraception. JBRA assisted reproduction, 23(4), 418–429.
[2] Vassilakopoulou, M., Boostandoost, E., Papaxoinis, G., de La Motte Rouge, T., Khayat, D., & Psyrri, A. (2016). Anticancer treatment and fertility: Effect of therapeutic modalities on reproductive system and functions. Critical reviews in oncology/hematology, 97, 328–334.
[3] Letourneau, J. M., Ebbel, E. E., Katz, P. P., Katz, A., Ai, W. Z., Chien, A. J., Melisko, M. E., Cedars, M. I., & Rosen, M. P. (2012). Pretreatment fertility counseling and fertility preservation improve quality of life in reproductive age women with cancer. Cancer, 118(6), 1710–1717.
[4] Quinn, G. P., Vadaparampil, S. T., Bell-Ellison, B. A., Gwede, C. K., & Albrecht, T. L. (2008). Patient-physician communication barriers regarding fertility preservation among newly diagnosed cancer patients. Social science & medicine (1982), 66(3), 784–789.
[5] Bussies, P. L., Richards, E. G., Rotz, S. J., & Falcone, T. (2022). Targeted cancer treatment and fertility: effect of immunotherapy and small molecule inhibitors on female reproduction. Reproductive biomedicine online, 44(1), 81–92.
[6] Okada, K., & Fujisawa, M. (2019). Recovery of Spermatogenesis Following Cancer Treatment with Cytotoxic Chemotherapy and Radiotherapy. The world journal of men's health, 37(2), 166–174.
[7] Jefferys, A., & Besley, C. (2020). Clinical Guideline: Fertility Preservation & Premature Gonadal Failure In Recipients Of Systematic Anti-Cancer Therapy. University Hospitals Bristol and Weston.
Acknowledgements
Guidance written by Dr Nick Lafferty
We would like to thank Dr. Amanda Jefferys, Dr. Caroline Besley, and Dr. Claire Burney at University Hospitals Bristol and Weston, who produced the clinical guideline entitled ‘Fertility Preservation & Premature Gonadal Failure in Recipients of Systematic Anti-Cancer Therapy’, on which this document was based.