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Fertility Preservation Before Cancer Treatment: Aspirations Versus Attainment

Leslie Schover, PhD, and Terri Lynn Woodard, MD

Dr. Leslie Schover is a clinical psychologist expert in reproductive health and cancer. She is retired from her academic career and is in private practice.

Dr. Terri Lynn Woodard is a reproductive endocrinologist and director of the Oncofertility Program at The University of Texas MD Anderson Cancer Center.

Dr. Leslie Schover was employed by Will2Love, LLC, during the past 2 years. Dr. Schover owned stock or held an ownership interest in Will2Love, LLC during the past 2 years. Dr. Schover has been paid honoraria by FemmePharma, currently or during the past 2 years.

Dr. Terri Lynn Woodard: None disclosed.

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Dr. Leslie Schover

Article Highlights:

  • A major gap remains between guidelines advocating for information and counseling on fertility preservation for all patients at risk of cancer-related infertility and the reality of practice in oncology settings.
  • Only a minority of eligible patients are referred for fertility preservation, with even fewer cryopreserving genetic material and exceptionally low rates of utilizing stored material to attempt conception.
  • Oncology settings need multidisciplinary programs that ensure collaboration between oncology and fertility specialists; national organizations should produce high-quality patient education materials and decision aids tailored to particular groups; and expert mental health professionals should be included in oncofertility programs.

For many people, becoming a parent is a central feature of adult identity and life goals. Young people typically assume that future parenthood is possible. Yet the diagnosis and treatment of cancer impairs or destroys fertility in many children, teens, and young adults.1,2 As age at first childbirth increases, infertility after cancer is an increasing concern for women and for men with malignancies such as prostate or colon cancer.

This editorial focuses on fertility preservation by cryopreserving genetic material. Advances in assisted reproductive technology have made it feasible to cryopreserve sperm, oocytes, embryos, or ovarian tissue prior to initiating gonadotoxic cancer treatment. Guidelines from ASCO3 and the European Society for Medical Oncology4 agree that all patients at risk for cancer-related infertility should be informed of their risk as early as possible in treatment planning and referred to reproductive specialists for possible fertility preservation. Discussions should be documented in the medical record. Patients should be given written or online educational materials and decision aids to facilitate informed decision-making. Children can be offered experimental options, such as freezing of testicular tissue, as part of clinical trials if potential benefits outweigh risks. Parental consent and children's age-appropriate assent should be obtained.

Dr. Terri Lynn Woodard

The Psychosocial Consequences of Cancer-Related Infertility

Infertility after cancer is associated with long-term emotional distress and poorer quality of life for men and women, particularly those left childless.5,6 Qualitative interview studies have identified a number of common themes, including infertility as a loss of control over future goals, a threat to masculine or feminine roles, and a barrier to existing or new romantic relationships.5,7-9 Fertility preservation represents hope for biologic offspring and a restored sense of control, but also introduces other stressors such as continued uncertainty about parenthood in the future, financial strain, the need to make a decision at a time of overwhelming stress from a new cancer diagnosis, and the potential physical and emotional burden associated with procedures required to store gametes.

Unmet Patient Needs for Information

Making a good choice about preserving fertility requires accurate information about risk of infertility after cancer treatment, in-depth education about fertility preservation options, and the opportunity for values clarification. The oncology team, patient's family members, and religious leaders or bioethicists also may facilitate decision-making.

Despite current clinical practice guidelines, a significant number of men and women are not informed of their risk of future infertility and are not offered consultation on fertility preservation.10 In a recent ASCO Quality Oncology Practice Initiative survey of 400 oncology settings,11 records for 6,976 patients of reproductive age revealed that only 56% of women and 32% of men were counseled about their risk of infertility. Information was more likely to be provided if the patient had a breast or hematologic cancer, was younger, and was seen in an academic setting that offered clinical trials and included a multidisciplinary fertility preservation program. Discussions were more frequent (49% vs. 40% of patients) in states with mandated insurance coverage of fertility preservation. In Sweden, a health system more centralized and less prone to health disparities in care than in the United States, a population-based survey of 1,010 young adults reported a much higher rate of counseling on fertility risks (81% of men and 78% of women).12 Still, only 15% of women, compared with 71% of men, cryopreserved genetic material. Women who were older, already had at least one child, or who were not heterosexual were less likely to be counseled. In addition, both men and women born outside of Sweden were less likely to receive information.

Despite current clinical practice guidelines, a significant number of men and women are not informed of their risk of future infertility and are not offered consultation on fertility preservation.10 The most effective practice model is to promote routine collaboration between the oncology team and fertility specialists.18

Table. A Summary of Knowledge and Utilization of Fertility Preservation
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Surveys of oncologists and patients suggest that less information is provided to patients who are less affluent or less educated, are non-White, belong to sexual minority groups, already have at least one child, or have a poor cancer prognosis.13-15 Two recent reviews highlighted the lack of easily accessible, high-quality decision aids and educational materials, particularly brochures or web sites tailored to specific populations of patients, with appropriate reading levels.16,17 Feasibility studies have been published of at least nine decision aids.17 Yet few randomized efficacy trials followed. Web-based information on oncofertility is highly variable in quality and often quite technical in language.16

Low Utilization of Fertility Preservation Consults, Procedures, and Stored Gametes

Research to evaluate utilization and outcomes of fertility preservation is hampered by difficulty collecting unbiased, population-based samples or recruiting patients with cancer and their loved ones for surveys during a time of incredible stress. Specialized oncofertility programs only exist in a minority of medical settings. A major gap remains between the aspiration of fertility preservation guidelines and the attainment of access and utilization of fertility preservation, even in high-income countries, including the United States.18

Referrals for fertility preservation consults remain the exception rather than the rule. With so many patients uninformed of their risk of infertility, how can we accurately estimate the percentage who are referred for specialized counseling (for example, with a trained advanced practitioner) or to a fertility clinic to discuss cryopreserving sperm, oocytes, embryos, or ovarian tissue? Six studies published since 1999 found that only 4% to 31% of eligible patients with cancer were referred for consultation on fertility preservation, with no clear trends by gender or recency of the data.15,19-23 Even among patients who had some counseling, a large group, especially women, were dissatisfied with the information received.24

Rates of fertility preservation are even more dismal. Seven studies of oocyte, embryo, or ovarian tissue freezing in cohorts of eligible patients with cancer in the United States, Canada, and Europe reported utilization rates from 5% to 41%.14,19,23,25-28 Rates of sperm banking ranged from 11% to 24%.21,22,29,30 Common barriers to fertility preservation include knowledge deficits, time constraints, and cost (Table).

Long-term follow-ups published by sperm banks or fertility clinics agree that only a small minority of men or women who cryopreserve gametes use their material to try for a pregnancy. A certain percentage of patients die of their disease and a larger minority have children by spontaneous pregnancy or using assisted reproduction after cancer. Ten long-term follow-ups of survivors' utilization of banked sperm in the United States, United Kingdom, and Europe have been published since 2003. Only 4% to 7% of men returned to use their samples.31-40 Ovarian tissue cryopreservation and subsequent autotransplantation to restore fertility and hormonal production is no longer considered experimental, with a review suggesting a 40% cumulative live birth rate.41 However, only a small minority of women (1% to 12%) who store ovarian tissue have returned for autotransplantation.42-48 Women's utilization of cryopreserved embryos or oocytes is only slightly more frequent (6% to 29%).27,28,42,47,49 Only a small minority of patients undergo testing to provide an accurate idea of their fertility potential after they have finished cancer treatment.47,50

It is difficult to document how often patients are offered modifications in cancer treatment intended to spare fertility, such as conization or radical trachelectomy for cervical cancer, unilateral oophorectomy for some types of ovarian cancer, hormonal treatment of early-stage uterine cancer, or active surveillance for testicular or prostate cancer.3,4 Adjuvant gonadotropin-releasing hormone analogs to prevent ovarian damage during chemotherapy remain controversial but are used fairly frequently.51 Such options are more likely to be offered in academic cancer centers, with similar biases for access by affluent or well-insured patients.

Improving Access to Fertility Counseling and Preservation Before Cancer

Patients need more systematic access to information about their risk of cancer-related infertility and their options for fertility preservation. The most effective practice model is to promote routine collaboration between the oncology team and fertility specialists.18 Many programs train an advanced practitioner or nurse navigator to provide counseling sessions for patients during treatment planning, with a subsequent visit to an andrologist or reproductive endocrinologist for those seriously considering cryopreservation. Programs that focus on a particular population, such as young women with breast cancer52 or adolescents and young adults,53,54 have reported success in increasing the rates of counseling on infertility risk and utilization of fertility preservation. Unfortunately, training in oncofertility is far from extensive in oncology fellowships55 or for allied health professionals.56

Providing in-depth counseling with trained personnel is one proven way to increase access to fertility preservation. Patients also benefit from supplemental educational materials to help them understand how cancer treatment can damage fertility, options to try to preserve fertility, and ways to clarify their values about future parenthood and using assisted reproductive technology.18 Materials should be tailored for patients' age range, level of health literacy, and sexual or gender minority status. Professional organizations such as ASCO should invest the time and funds to create optimal patient education, keeping in mind that the digital divide still exists and, thus, both online and print versions are needed.

Valuing Emotional Support

Expert mental health professionals can help patients cope with threats to their fertility, clarify their values, and overcome distress when parenthood is interrupted.18 Unfortunately, most oncofertility programs do not have such a team member. Insurance coverage for mental health services remains limited. Research is needed to document that mental health care prevents suffering and lost productivity and can decrease utilization of medical care.

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