- 1 Introduction
- 1.1 Purpose of this guidance
- 1.2 Population covered
- 1.3 The need for practice guidance
- 1.4 Statement of intent/disclaimer
- 1.5 Remit (Scope)
- 1.6 Development and review of the guidance
- 1.7 Ethical, legal, technical and cost considerations
- 1.8 References
This guidance has been developed for oncologists and health professionals involved in the management of adolescents and young adults (AYA) diagnosed with cancer.
If you are an AYA cancer patient, survivor or family member seeking information about fertility preservation and related issues, we have provided links to recommended information.
Many cancers that present in adolescents and young adults (AYAs) can be successfully treated. Unfortunately many of the cancer therapies recommended for AYAs have the potential to cause impaired fertility in the short or long term.
There is clear evidence that young people with cancer are concerned about the potential impact of their cancer diagnosis and treatment on their future fertility  and wish to be given information about these issues at an early stage in their management.
To optimise outcomes for young patients, health professionals need to provide timely and full information about fertility risks, preservation options and related issues with particular focus on:
- making the discussion effective and age-specific
- directing information and decisions to the AYA patient
- identifying and addressing individual patient factors and concerns.
AYA patients and their families should be given written information and offered psychosocial support.
For females, the major effect of cancer treatment on reproductive potential is via damage to the ovary and the oocytes with accelerated oocyte depletion. This can result in temporary or permanent ovarian failure and early menopause.
For males, the major cause of impaired fertility is chemotherapy- or radiation-induced damage to sperm.
Therapies associated with the greatest risks to male and female fertility are:
- alkylating chemotherapy agents
- total body irradiation (as used in myeloablative stem-cell transplantation) and high dose pelvic radiotherapy.
In many cases fertility preservation is possible. There is a range of procedures and processes to preserve or protect the fertility of young men and women diagnosed with cancer. The options available depend on many factors including the patient’s gender, age, relationship status, type of cancer and type of treatment.
The most effective and established means of preserving fertility in young people with cancer are:
- oocyte and embryo cryopreservation where appropriate for females
- sperm cryopreservation for males before cancer treatment starts.
Most other procedures are still considered somewhat investigational including ovarian tissue grafting. There is increasing evidence that ovarian suppression prior to chemotherapy may help to preserve fertility.
After cancer treatment ends all AYA cancer survivors should have access to regular monitoring and assessment of reproductive, endocrine and sexual health.
Females who have had cancer treatment should be counseled that they may have a shortened reproductive life span with an earlier menopause. Pregnancy following cancer should generally be managed by a multidisciplinary team as a ‘high risk’ pregnancy.
Research to date suggests that a history of cancer, cancer treatment or fertility preservation interventions does not increase the risk of birth defects, genetic disorders or chromosomal abnormalities in a survivors’ progeny. In hormone sensitive cancers such as breast cancer, research to date does not show that a pregnancy leads to a worse outcome for the mother or baby.
Reduced fertility or loss of fertility due to cancer treatment may lead to emotional distress  and early referral for counseling is recommended.
Purpose of this guidance
This guidance aims to:
- provide succinct information for health professionals about the risks to fertility of cancer treatments
- provide information about current and likely future fertility preservation options for AYAs diagnosed with cancer
- make recommendations for discussing risks, options and related issues with AYA patients
- make recommendations for monitoring AYA cancer survivors’ reproductive, sexual and endocrine health after cancer treatment ends and providing necessary referrals and support.
It includes links to more detailed information and resources for health professionals, and to educational resources for AYA patients and their families.
This guidance is applicable to all adolescents and young adults – aged between 15 and 24 years of age – diagnosed with cancer of any type. Most of the recommendations are applicable to all patients diagnosed with cancer during their reproductive life years. See Remit for discussion about fertility preservation for patients aged under 15 years.
Wherever possible this guidance acknowledges individual patient factors that affect risk (such as age and cancer type) and decision-making (such as cultural background and belief systems). It highlights the importance of personalised assessment and management plans, based on assessment of the patient’s needs and preferences and consultation with the multidisciplinary team.
The need for practice guidance
Infertility is a significant and distressing effect of cancer treatment for some survivors of childhood and AYA cancers.
Given the known risk to fertility of many cancer treatments, and the fact that fertility preservation may be possible, it is important that all AYA patients are appropriately and fully informed of these risks and the options available for preserving their fertility before treatment begins.
Studies suggest that currently many health care professionals do not routinely discuss infertility and options for fertility preservation, even though they recognise the importance of doing so. Stated barriers include lack of time, lack of information about fertility preservation methods and costs, not knowing where to refer patients for fertility preservation, and concern about costs to patients and treatment delays due to fertility preservation efforts.
According to international literature, about 30% to 60% of AYAs with cancer do not recall receiving information about the risk of infertility or options for fertility preservation – which suggests that information is either not offered or that it was ‘lost among the overwhelming nature and amount of information’ provided at the time of diagnosis and before treatment. Many patients who do recall infertility discussions were dissatisfied with the quality and amount of information provided.
Statement of intent/disclaimer
This guidance is a general guide to appropriate practice and potential options. Patient management must be personalised in consultation with the patient, their caregivers and the multidisciplinary treatment team.
Our aim is to provide guidance that is succinct, simple, practical and evidence-based. We have highlighted where evidence is lacking and recommendations are based on consensus of an expert panel and comprehensive review of the international literature, international guidelines and current best practice.
The guidance has been developed for Australian practice and is applicable nationally, subject to the need for local protocols for all health professionals involved in AYA cancer management.
This guidance provides information and recommendations about five key areas:
- Discussing fertility with AYAs diagnosed with cancer
- Managing the fertility preservation process
- Impact of cancer treatments on reproductive and hormonal functions
- Options for protecting/preserving fertility in AYAs diagnosed with cancer
- Long term monitoring and follow up care
The guidance is intended for health professionals managing AYA patients diagnosed with cancer so it is restricted to information about options for fertility preservation and does not specifically address methods of fertility restoration after treatment.
For the purpose of this guidance, we have used the Youth Cancer Networks Program definition of the age range for AYA patients as 15 to 24 years. The COSA working group stressed the importance of highlighting fertility preservation issues for pre-pubertal patients and their families, particularly the implications of cancer treatments on gynaecological/andrological function and reproductive capacity, and also fertility preservation.
Some of the information and recommendations in this guidance may be applicable to younger males and females during puberty. However the options presently available to pre-pubertal children are limited by their sexual immaturity and remain investigational.
These guidelines are also broadly applicable to older patients (i.e. older than 24 years of age) in the potentially reproductive age group.
In developing this guidance, the COSA working group identified the need for:
- More clinical research, particularly well conducted studies evaluating:
- the risk of cancer treatments to fertility and endocrine function in both the short and longer term
- actions and protective benefits of medical options
- fertility and pregnancy impacts of various preservation strategies
- Funding for resources to preserve fertility e.g. sperm banking
- Education programs to increase health professional and consumer awareness of the risk of infertility for cancer patients and options for fertility preservation.
Development and review of the guidance
This guidance has been produced by the Clinical Oncological Society of Australia (COSA) as part of a national Youth Cancer Networks Program project funded by the Australian Government.
COSA convened a working group of multidisciplinary health professionals with expert knowledge of the areas covered and a patient representative with personal experience to review the available literature and develop the guidance.
Guidance working group members
Dr Kate Stern MBBS FRANZCOG FRCOG CREI (Chair)
Gynaecologist, reproductive endocrinologist and fertility specialist
Head of Clinical Research, Melbourne IVF
Coordinator of the medical fertility preservation program at Royal Women’s Hospital Melbourne and Melbourne IVF
Professor Peter Bardy
Kate Bourne BSW
Chairperson of the Australian and New Zealand Infertility Counsellors Association
Oncology Social Worker, Monash Medical Centre
Senior Community Education Officer, Victorian Assisted Reproductive Treatment Authority
Dr Peter Downie
Chair, Australian and New Zealand Children's Haematology-Oncology Group
Director, Clinical Oncology Royal Children's Hospital, Parkville
Medical Director, Victorian Paediatric Integrated Cancer Service
Head, Children's Cancer Centre and Head of Unit, Paediatric Haematology-Oncology, Monash Children's, Monash Medical Centre, Clayton
Professor Roger Hart MD FRANZCOG MRCOG CREI
Professor of Reproductive Medicine
School of Women's and Infants Health, University of Western Australia
Medical Director of Fertility Specialists of Western Australia and Fertility Specialists South
Professor Martha Hickey MBChB MD FRANZCOG
Professor of Obstetrics and Gynaecology
The Royal Women's Hospital and The University of Melbourne
AYA cancer survivor
CanTeen Board Director and patient representative
Professor Robert McLachlan PhD FRACP
Endocrinologist and reproductive biologist
Director, Andrology Australia
Principal Research Fellow, Prince Henry's Institute
Consultant Andrologist, Monash IVF, Melbourne
Gillian Myles RN RSCN BN (January to June 2011)
Clinical Nurse Consultant, Adolescent And Young Adult Service
Princess Alexandra Hospital, Brisbane
Yvonne Panek-Hudson RN MN
Allograft Nurse Practitioner
Peter MacCallum Cancer Centre, Melbourne
Dr Marianne B Phillips MBCHB FRCP FRCPCH FRACP
Consultant Paediatric & Adolescent Oncologist and Palliative Care Specialist
Princess Margaret Hospital for Children
Lead Clinician Adolescent & Young Adult Collaborative, WA Cancer & Palliative Care Network
Professor John F. Seymour MBBS PhD FRACP
Head, Haematology Department and Chair, Haematology Service
Division of Cancer Medicine
Peter MacCallum Cancer Centre, Melbourne
Dr Howard Smith MBBS BSc(Med) PhD FRACP
Head of Department of Reproductive Medicine
Director Westmead Fertility Centre
Westmead Hospital, Sydney
Aaron Thompson RN/BN PG Cert AYACC (Sept–Dec 2010)
Clinical Nurse Consultant, After Cancer Therapy Service (Sept 2008 to Dec 2010)
Queensland Children's Cancer Centre, Brisbane
Guidance development team
Ms Lisa Herron (Writer/editor)
Ms Alice Winter-Irving (Literature review)
Project Officer, Clinical Guidelines Network
Cancer Council Australia
The working group followed a process based on the National Health and Medical Research Council (NHMRC) recommendations for developing clinical practice guidelines, but modified to suit our purpose and format (succinct and web-based only).
The working group members considered the results of a literature search and, wherever possible recommendations are based on evidence and are graded according to the NHMRC grades. However the literature is limited, mainly comprising cohort studies and case reports and very few randomised trials. Hence most recommendations in this guidance are based on expert consensus and are identified as ‘Practice Points’ (PP).
The draft guidance was posted on Cancer Council Australia’s Wiki site that is hosting COSA's AYA guidances. The guidelines were widely promoted for public consultation on the wiki from 3 to 31 May 2011. An invitation to review the guidance, with a link to the site, was disseminated to all stakeholders and target users including members of the AYA Cancer Network and all COSA members.
COSA will monitor for new evidence related to the areas covered by this guidance and ask members of the working group or other experts to review relevant literature and advise if the content and recommendations need to be updated or amended.
Process of developing AYA clinical guidance
- Working group established to confirm and advise on the purpose and scope of the guidelines, target audience, issues and interventions to be considered and desired outcomes.
- Systematic literature review and review of existing guidelines, resources and other relevant documents.
- Working group reviewed evidence and provided advice re content and structure of the guideline.
- Working group drafted the guideline content, with assistance of writer/editor.
- Working group members reviewed content and developed recommendations.
- Draft guidance posted on Cancer Council Australia's Wiki platform, that is hosting COSA's AYA guidances, and made available to a broader group of interested individuals and organisations for review and consultation.
- Working group and writer reviewed comments and amended guidance as required.
- Guidance submitted to Australian Government Department of Health and Ageing for review.
- Working group members provided advice regarding dissemination and promotion of the guideline and developed strategy for evaluation and revision.
- Guidance published (made live on COSA website).
Literature search: Methods and selection
A literature search was conducted in August and September 2010 to identify relevant meta-analyses, systematic reviews, randomised controlled trials, clinical trials, cohort studies, reviews and evidence based guidelines for the following clinical questions (developed by the working group):
- Do fertility preservation treatments in adolescent and young adult cancer patients significantly increase their ability to conceive later in life?
- What impact do fertility preservation measures have on delay of treatment initiation? Are these delays safe and/or appropriate?
- What is the impact of fertility preservation measures (and subsequent pregnancy) on disease recurrence (primarily applicable to breast cancer)?
- Is there a potential for disease contamination of harvested ovarian tissue (primarily applicable to haematological malignancies i.e. leukaemia, lymphoma, myeloma)?
- Is it safe to collect ovarian tissue and sperm after the onset of chemotherapy?
- What is the psychosocial and psychological impact on patients who did/did not undertake fertility prevention measures?
- When is it appropriate/ optimal to undergo fertility preservation procedures? i.e. in cases of disease relapse or premature ovarian failure.
- What are the long term issues of fertility preservation? When is fertility reassessed? What are the other options e.g. adoption and sperm/egg donation.
- What is the impact of fertility preservation on hormonal function in males and females? Are there adverse effects (other than reproductive function)?
- What is the best practice approach for discussion/communication of fertility preservation with AYAs?
Databases searched included PubMed, Embase, PsycINFO, CINAHL, Cochrane Library and TRIP Database. The following search terms were used:
MeSH: adolescent, young adult, neoplasms (exploded), survivors, fertility, infertility, conization, cryopreservation, gonadotropin-releasing hormone, hormone replacement therapy, oocyte retrieval, organ preservation, ovariectomy, tissue preservation, reproductive techniques, reproductive techniques assisted, antineoplastic agents/adverse effects, amenorrhea, menopause premature, primary ovarian insufficiency, pregnancy, psychology, recurrence, adoption, time.
Emtree: adolescent, adult, boy, girl, juvenile, neoplasm (exploded), fertility, infertility, subfertility, survivor, cryopreservation, preservation, cystectomy, radiation shield, uterine cervix conization, ovariectomy, oocyte retrieval, gonadorelin, sperm preservation, ovary insufficiency, adoption, amenorrhea and oligomenorrhea, early menopause, premature ovarian failure, aspermia, asthenospermia, azoospermia, oligospermia, pregnancy, cancer recurrence, cancer relapse, psychology, psychosocial care, therapy delay, time, interpersonal communication, interdisciplinary communication.
Free text: girls, boys, juvenile, teenager, AYA, cancer, preserv*, survivorship, GnRH, cervicectomy, oncofertility, oophoropexy, ovarian cystectomy, ovarian suppression, tissue freezing, ovarian transplantation, radiation shielding, trachelectomy, premature ovarian failure, ovulatory dysfunction, reproduction ability, subfertility, subfertile, sterile, delay, discuss*, communicat*, psychosocial, relapse, long term effects.
Reference lists of key papers and PubMed related citations were reviewed for additional papers.
Studies were included if they were published after 2005 and if the age range was between 15 and 25.
The search yielded 173 articles consisting of 2 meta-analyses, 5 systematic reviews, 3 randomised controlled trials, 17 clinical trials, 27 research support studies, 6 cohort studies, 6 case series, 16 qualitative surveys, 9 evidence-based guidelines, 69 review articles and 13 other studies.
Grading of recommendations
In developing the recommendations in this guidance, the working group has assigned NHMRC grades of recommendation to assist users to distinguish between those based on strong evidence, and those based on weak evidence.
The grade does not indicate the importance of the recommendation, but reflects the strength of the evidence supporting it. It indicates to users the likelihood that, if that recommendation is implemented, the predicted outcome will be achieved. So, NHMRC grade A and B recommendations are generally based on a body of evidence that can be trusted to guide clinical practice, whereas Grade C and D recommendations must be applied carefully to individual clinical and organisational circumstances and should be followed with care.
Given the low volume and/or quality of evidence relating to some of the questions this guidance addresses, the working group identified several important practice recommendations for which there is not, nor is there likely to be, any research evidence. The working group considered these aspects of management to be ‘such sound clinical practice that nobody is likely to question it’ or ‘clinical common sense’.  These are identified as Practice Points (PP).
|A||Body of evidence can be trusted to guide practice|
|B||Body of evidence can be trusted to guide practice in most situations|
|C||Body of evidence provides some support for recommendation(s) but care should be taken in its application|
|D||Body of evidence is weak and recommendation(s) must be applied with caution|
|PP*||A ‘practice point’ – where there is no evidence, but it is ‘clinical common sense’.|
Ethical, legal, technical and cost considerations
There are many ethical, legal and technical considerations regarding interventions to preserve and protect fertility. Wherever possible these are acknowledged in the relevant section of the guidance.
Where a recommended diagnostic or management therapy is not approved for funding by the Australian Pharmaceutical Benefits Scheme (PBS) this is noted in the guidance.
- Multidisciplinary Working Group convened by the British Fertility Society. A strategy for fertility services for survivors of childhood cancer Hum Fertil (Camb) 2003 May;6(2):A1-A39 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12869793].
- Lee SJ, Schover LR, Partridge AH, Patrizio P, Wallace WH, Hagerty K, et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients J Clin Oncol 2006 Jun 20;24(18):2917-31 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16651642].
- Thewes B, Meiser B, Rickard J, Friedlander M. The fertility- and menopause-related information needs of younger women with a diagnosis of breast cancer: a qualitative study Psychooncology 2003;12(5):500-11 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12833562].
- Partridge AH, Gelber S, Peppercorn J, Sampson E, Knudsen K, Laufer M, et al. Web-based survey of fertility issues in young women with breast cancer J Clin Oncol 2004 Oct 15;22(20):4174-83 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15483028].
- Levine J, Canada A, Stern CJ. Fertility preservation in adolescents and young adults with cancer J Clin Oncol 2010 Nov 10;28(32):4831-41 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20458029].
- Schover LR, Brey K, Lichtin A, Lipshultz LI, Jeha S. Knowledge and experience regarding cancer, infertility, and sperm banking in younger male survivors J Clin Oncol 2002 Apr 1;20(7):1880-9 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11919248].
- Scottish Intercollegiate Guidelines Network. SIGN 50: A guideline developer’s handbook. Section 7. 2008;Accessed 21 October 2010. [Abstract available at http://www.sign.ac.uk/guidelines/fulltext/50/section7.html].