Fertility Preservation in Patients With Cancer

Publication Date: April 5, 2018
Last Updated: December 16, 2022

Treatment

Recommendation 1.1

People with cancer are interested in discussing fertility preservation. Health care providers caring for adult and pediatric patients with cancer (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, surgeons, and others) should address the possibility of infertility as early as possible before treatment starts.
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Recommendation 1.2

Health care providers should refer patients who express an interest in fertility preservation (and those who are ambivalent) to reproductive specialists.
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Recommendation 1.3

To preserve the full range of options, fertility preservation approaches should be discussed as early as possible, before treatment starts. The discussion can ultimately reduce distress and improve quality of life. Another discussion and/or referral may be necessary when the patient returns for follow-up after completion of therapy and/or if pregnancy is being considered. The discussions should be documented in the medical record.
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Adult Men

Recommendation 2.1

Sperm cryopreservation: Sperm cryopreservation is effective, and health care providers should discuss sperm banking with postpubertal males receiving cancer treatment.
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Recommendation 2.2

Hormonal gonadoprotection: Hormonal therapy in men is not successful in preserving fertility. It is NOT recommended.
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Recommendation 2.3

Other methods to preserve male fertility: Other methods, such as testicular tissue cryopreservation and reimplantation or grafting of human testicular tissue, should be performed only as part of clinical trials or approved experimental protocols.
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Recommendation 2.4

Post-chemotherapy: Men should be advised of a potentially higher risk of genetic damage in sperm collected after initiation of therapy. It is strongly recommended that sperm be collected before initiation of treatment because the quality of the sample and sperm DNA integrity may be compromised after a single treatment. Although sperm counts and quality of sperm may be diminished even before initiation of therapy, and even if there may be a need to initiate chemotherapy quickly such that there may be limited time to obtain optimal numbers of ejaculate specimens, these concerns should not dissuade patients from banking sperm. Intracytoplasmic sperm injection allows the future use of a very limited amount of sperm; thus, even in these compromised scenarios, fertility may still be preserved
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Adult Women

Recommendation 3.1

Embryo cryopreservation: Embryo cryopreservation is an established fertility preservation method, and it has routinely been used for storing surplus embryos after in vitro fertilization.
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Recommendation 3.2

Cryopreservation of unfertilized oocytes: Cryopreservation of unfertilized oocytes is an option and may be especially well suited to women who do not have a male partner, do not wish to use donor sperm, or have religious or ethical objections to embryo freezing.

Oocyte cryopreservation should be performed in centers with the necessary expertise. As of October 2012, the American Society for Reproductive Medicine no longer deems this procedure experimental.
Qualifying Statement: More flexible ovarian stimulation protocols for oocyte collection are now available. Timing of this procedure no longer depends on the menstrual cycle in most cases, and stimulation can be initiated with less delay compared with old protocols. Thus, oocyte harvesting for the purpose of oocyte or embryo cryopreservation is now possible on a cycle day-independent schedule. Of special concern in estrogen-sensitive breast and gynecologic malignancies is the possibility that these fertility preservation interventions (e.g., ovarian stimulation regimens that increase estrogen levels) and/or subsequent pregnancy may increase the risk of cancer recurrence. Aromatase inhibitor-based stimulation protocols are now well-established and may ameliorate this concern. Studies do not indicate increased cancer recurrence risk as a result of aromatase-inhibitor supplemented ovarian stimulation and subsequent pregnancy.
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Recommendation 3.3

Ovarian transposition: Ovarian transposition (oophoropexy) can be offered when pelvic irradiation is performed as cancer treatment. However, because of radiation scatter, ovaries are not always protected, and patients should be aware that this technique is not always successful.

Because of the risk of remigration of the ovaries, this procedure should be performed as close to the time of radiation treatment as possible.
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Recommendation 3.4

Conservative gynecologic surgery: It has been suggested that radical trachelectomy (surgical removal of the uterine cervix) should be restricted to stage IA2 to IB cervical cancer with diameter <2 cm and invasion < 10 mm.

In the treatment of other gynecologic malignancies, interventions to spare fertility have generally centered on doing less radical surgery with the intent of sparing the reproductive organs as much as possible. Ovarian cystectomy can be performed for early-stage ovarian cancer.
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Recommendation 3.5 [Updated]

Ovarian suppression: There is conflicting evidence to recommend GnRHa and other means of ovarian suppression for fertility preservation. The Panel recognizes that, when proven fertility preservation methods such as oocyte, embryo or ovarian tissue cryopreservation are not feasible, and in the setting of young women with breast cancer, GnRHa may be offered to patients in the hope of reducing the likelihood of chemotherapy-induced ovarian insufficiency. However, GnRHa should not be used in place of proven fertility preservation methods.
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Recommendation 3.6 [Updated]

Ovarian tissue cryopreservation and transplantation: Ovarian tissue cryopreservation for the purpose of future transplantation does not require ovarian stimulation and can be performed immediately. In addition, it does not require sexual maturity and hence may be the only method available in children. Finally, this method may also restore global ovarian function. However, it should be noted further investigation is needed to confirm whether it is safe in patients with leukemias.
Qualifying Statement: As of the time of this publication, ovarian tissue cryopreservation remains experimental. However, emerging data may prompt reconsideration of this designation in the future. (This technique is already considered non-experimental in some countries and its experimental status is undergoing evaluation in the U.S.)
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Role of Health Care Providers

Recommendation 4.1

All oncologic health care providers should be prepared to discuss infertility as a potential risk of therapy. This discussion should take place as soon as possible once a cancer diagnosis is made and can occur simultaneously with staging and the formulation of a treatment plan. There are benefits for patients in discussing fertility information with providers at every step of the cancer journey.
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Recommendation 4.2

Encourage patients to participate in registries and clinical studies, as available, to define further the safety and efficacy of these interventions and strategies.
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Recommendation 4.3

Refer patients who express an interest in fertility, as well as those who are ambivalent or uncertain, to reproductive specialists as soon as possible.
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Recommendation 4.4

Refer patients to psychosocial providers when they are distressed about potential infertility.
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Special Considerations: Children

Recommendation 5.1

Suggest established methods of fertility preservation (e.g., semen or oocyte cryopreservation) for postpubertal children, with patient assent and parent or guardian consent. For prepubertal children, the only fertility preservation options are ovarian and testicular cryopreservation, which are investigational.
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Recommendation Grading

Overview

Title

Fertility Preservation in Patients With Cancer

Authoring Organization

Publication Month/Year

April 5, 2018

Last Updated Month/Year

December 16, 2022

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Patients with cancer at risk for infertility due to anticancer treatment.

Target Provider Population

Oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, surgeons, nurses, social workers

Inclusion Criteria

Male, Female, Adolescent, Adult, Child

Health Care Settings

Ambulatory, Hospital, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant, psychologist, social worker

Scope

Management, Prevention

Keywords

cancer, fertility preservation, infertility, anticancer treatment

Source Citation

DOI: 10.1200/JCO.2018.78.1914 Journal of Clinical Oncology 36, no. 19 (July 01, 2018) 1994-2001.

Supplemental Methodology Resources

Data Supplement, Methodology Supplement

Methodology

Number of Source Documents
48
Literature Search Start Date
January 1, 2013
Literature Search End Date
December 31, 2017
Description of External Review Process
ASCO has a rigorous review process for guidelines. After the draft has been approved by the Expert Panel, the guideline is independently reviewed and approved by the Clinical Practice Guideline Oversight Committee (CPGC). Select members of the CPGC are asked to critically review the guideline prior to the next scheduled CPGC meeting. The CPGC members then present the results of their reviews to the full committee, discuss the review with the full committee, and the CPGC votes on whether to approve the guideline (with recusals from members who have relationships with affected companies). Approved ASCO Guidelines are then submitted to the Society’s journal for consideration of publication.
Specialties Involved
Hematology, Obstetrics And Gynecology, Oncology, Pediatrics, Psychiatry, Urology, Pediatric Hematology Oncology, Surgical Oncology, Radiation Oncology, Hematology Oncology, Pediatrics, Oncology, Oncology, Hematology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
See full text.
Description of Study Criteria
See supplement.
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100