Ethical, legal, social, and policy issues of ovarian tissue cryopreservation in prepubertal girls: a critical interpretive review.

PURPOSE: Despite the increasing number of childhood cancer survivors, significant advances in ovarian tissue cryopreservation (OTC) technique and medical societies' recommendations, fertility preservation (FP) and FP discussions are not always offered as a standard of care in the pediatric context. The aim of this literature review is to understand what ethical, legal, social, and policy issues may influence the provision of FP by OTC in prepubertal girls with cancer. METHODS: A critical interpretive review of peer-reviewed papers published between 2000 and January 2023 was conducted, guided by the McDougall's version of the critical interpretive synthesis (Dixon-Woods), to capture recurring concepts, principles, and arguments regarding FP by OTC for prepubertal girls. RESULTS: Of 931 potentially relevant papers, 162 were included in our analysis. Data were grouped into seven thematic categories: (1) risks of the procedure, (2) unique decision-making issues in pediatric oncofertility, (3) counseling, (4) cultural and cost issues, and (5) disposition of cryopreserved reproductive tissue. CONCLUSION: This first literature review focusing on ethical, legal, social, and policy issues surrounding OTC in prepubertal girls highlights concerns in the oncofertility debate. Although OTC is no longer experimental as of December 2019, these issues could limit its availability and the child's future reproductive autonomy. This review concludes that specific actions must be provided to enable the offer of FP, such as supporting families' decision-making in this unique and complex context, and providing pediatric patients universal and full access to free or highly subsidized OTC.

Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Patients with childhood, adolescent, and young adult cancer who will be treated with gonadotoxic therapies are at increased risk for infertility. Many patients and their families desire biological children but effective communication about treatment-related infertility risk and procedures for fertility preservation does not always happen. The PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group reviewed the literature and developed a clinical practice guideline that provides recommendations for ongoing communication methods for fertility preservation for patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger and their families. Moreover, the guideline panel formulated considerations of the ethical implications that are associated with these procedures. Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the evidence and recommendations. In this clinical practice guideline, existing evidence and international expertise are combined to develop transparent recommendations that are easy to use to facilitate ongoing communication between health-care providers and patients with childhood, adolescent, and young adult cancer who might be at high risk for fertility impairment and their families.

Restricted access to assisted reproductive technology and fertility preservation: legal and ethical issues.

Access to assisted reproductive technology (ART) and fertility preservation remains restricted in middle and low income countries. We sought to review the status of ART and fertility preservation in Brazil, considering social indicators and legislative issues that may hinder the universal access to these services. Although the Brazilian Constitution expressly provides the right to health, and ordinary law ensures the state is obliged to support family planning, access to services related to ART and fertility preservation is neither easy nor egalitarian in Brazil. Only a handful of public hospitals provide free ART, and their capacity far from meets demand. Health insurance does not cover ART, and the cost of private care is unaffordable to most people. Brazilian law supports, but does not command, the state provision of ART and fertility preservation to guarantee the right to family planning; therefore, the availability of state-funded treatments is still scarce, reinforcing social disparities. Economic projections suggest that including ART in the Brazilian health system is affordable and may actually become profitable to the state in the long term, not to mention the ethical imperative of recognizing infertility as a disease, with no reason to be excluded from a health system that claims to be 'universal'.

A call to action: unified clinical practice guidelines for oncofertility care.

By 2030, WHO estimates that 1.4 million reproductive-aged women will be diagnosed with cancer annually. Fortunately, cancer is no longer considered an incurable disease in many cases. From 2008-2014, 85% of women under the age of 45 years diagnosed with cancer survived. This increase in survival rate has shifted attention from focusing exclusively on preserving life to focusing on preserving quality of life after treatment. One aspect of this is preserving the ability to have a biological family. Oncofertility, the field that bridges oncology and reproductive endocrinology with the goal of preserving fertility, offers these patients hope. Though it is clear that ASCO and ASRM recognize the importance of fertility preservation as an aspect of comprehensive oncology care, there are not yet unified guidelines for oncologists and fertility specialists for treating oncofertility patients. First, we identify the need for reproductive counseling prior to cancer treatment, as many patients report that their fertility preservation concerns are not addressed adequately. We then delineate multi-modal fertility preservation options that are available and appropriate for different patients with corresponding outcomes using different treatments. We discuss the unique challenges and considerations, including ethical dilemmas, for delivering timely and comprehensive care specifically for oncofertility patients. Finally, we address the multidisciplinary team that includes oncologists, reproductive endocrinologists, surgeons as well as their staff, nurses, genetic counselors, mental health professionals, and more. Since oncofertility patient care requires the coordination of both physician teams, one set of unified guidelines will greatly improve quality of care.

Elective Egg Freezing for Non-Medical Reasons: Scientific Impact Paper No. 63.

Although a woman's fertility declines markedly in her late-30s and early-40s, gradually more and more women start a family at this stage of their lives, with the average age of childbirth progressively increasing. More women are storing their eggs (oocytes) to give them the potential opportunity to have a baby in the future. Nonetheless, the number of egg freezing cycles accounts for less than 2% of IVF cycles, and the number of cycles using stored eggs is even lower. The technology for freezing eggs changed dramatically about a decade ago with the development of a technique of rapid freezing called vitrification, which gives success rates almost as good as using fresh eggs. The growing use of this technique, and the publicity surrounding how this technique may have been promoted, has led to this paper. It is essential that women are very clearly informed about the likely success rates of egg freezing, particularly as it is entirely provided by the private sector, with the associated concerns of financial costs and inappropriate or inaccurate marketing. Its success is strongly dependent on the age of the woman at the time of freezing her eggs, with much higher success rates in those aged 35 years and under. Current legislation only allows women to store eggs for 10 years, which conflicts with the better success rates when women do so at a younger age. The reasons behind the increase in egg freezing are complex, but the most common reason given by women storing eggs is that they do not have a partner and are concerned that by the time they do find themselves in a relationship within which they wish to start a family, they may not be able to. We conclude that elective egg freezing provides women with an opportunity to take action about the drop in their fertility, but at present most women who are doing this are already in their later 30s when the success rates are limited. We strongly support the need for improved and continuing education of both women and men regarding the decline in female fertility with age.

Ethical issues involving fertility preservation for transgender youth.

PURPOSE: To investigate ethical issues associated with fertility preservation (FP) in transgender youth based on reports of patients and their parents. METHODS: Our qualitative study involved in-person interviews with 54 subjects (35 patients and 19 parents). Interviews were audio recorded, transcribed, and verified. Each subject completed a demographic questionnaire, and each patient's medical chart was reviewed for additional information. We analyzed the data using inductive thematic content analysis. RESULTS: Themes that emerged included a range of desires and ambivalence about having genetically related children, variability in understanding the potentially irreversible impact of gender affirming hormones (GAHs) on fertility, use of adoption, and the impact of age on decision-making. Subjects (patients and parents) noted barriers to FP, such as cost and insurance coverage. Several parents expressed concern that their transgender children may have future regret about not attempting FP. Both transgender youth and their parents felt FP was an important precaution. CONCLUSIONS: Our study took advantage of the richness of personal narratives to identify ongoing ethical issues associated with fertility preservation in transgender youth. Transgender youth and their parents did not fully understand the process of FP, especially regarding the effects of GAHs, had fears that FP could reactivate gender dysphoria, and noted barriers to FP, such as cost, highlighting economic disparity and lack of justice. These findings highlight ethical issues involving the adequacy of informed consent and economic injustice in access to FP despite expressed interest in the topic.

Fertility preservation in the pediatric cancer patient.

PURPOSE OF REVIEW: Long-term survival rates from childhood cancers approach 85% with many of these patients now reaching adulthood and facing the consequences of prior cancer treatment including infertility. This highlights the importance of discussing fertility risk and presenting fertility preservation options prior to initiation of cancer treatment. This article reviews the current literature on fertility preservation in adolescents, young adults, and prepubertal patients. RECENT FINDINGS: Sperm banking remains the gold standard for fertility preservation in adolescents and young adults. Testicular sperm extraction and electroejaculation may also be utilized in patients that are unable to produce a semen sample. Fertility preservation options for prepubertal patients remain experimental but recent data illustrate the potential to restore spermatogenesis using spermatogonial stem cells. SUMMARY: Fertility risk and fertility preservation options for pediatric patients should be routinely discussed at the time of cancer diagnosis. Sperm preservation should be routinely offered to adolescents and young adults at risk for infertility from cancer treatment. Preservation of prepubertal spermatogonial stem cells can be offered as an experimental option.

Ethical issues in the care of adolescent and young adult oncology patients.

The diagnosis and treatment of cancer leads to short-term and long-term challenges for every patient. This is especially true for adolescents and young adults (AYAs) with cancer who strive to gain independence, autonomy, confidence, and social status while developing into adulthood. In this article, we review prominent ethical issues in AYA oncology that are related to autonomy, shared decision-making, care refusal or abandonment, end-of-life care, truth telling, and fertility preservation. Clinicians should recognize that AYA patients develop at their own pace; the onus lies with clinicians to determine the patient's interests, values, maturity, and desire to participate in decision-making.

Elective egg freezing without medical indications.

The aim of this review is to provide current knowledge on fertility preservation for non-medical reasons in women willing to postpone childbearing. The topic is highly debatable, starting from disagreement about its terminology, the number of eggs necessary to predict chances of success, and the safety and socio/ethical point of view. Cost analysis and discrepancies among countries' recommendations and regulations are described to confirm the controversies and unsolved issues around this very interesting topic. Finally, an overview on the returning rate of women among "egg bankers" and reasons behind their decisions are illustrated.

Conducting reproductive research during a new childhood cancer diagnosis: ethical considerations and impact on participants.

PURPOSE: Research among adults shows benefits and low perceived burden of engaging in behavioral research. However, questions remain regarding the ethics of conducting behavioral research in pediatric populations during sensitive situations, including during a new life-threatening diagnosis or at end-of-life. We examined reactions to participating in a behavioral reproductive research study among male adolescents newly diagnosed with cancer and their parents, as a step towards optimizing fertility preservation utilization in a population where future infertility is common. METHODS: Pediatric literature regarding the ethics of behavioral research was reviewed. In our pilot, forty-four participants (19 mothers, 11 fathers, 14 male adolescents newly diagnosed with cancer) from 20 families completed demographic questionnaires and a fertility preservation decision tool developed by the study team. Qualitative interviews exploring the impact of study participation were subsequently conducted. Verbatim transcripts were coded for thematic content using the constant comparison method. RESULTS: Literature review showed positive reactions to research participation among youth/caregivers. In our pilot study, 89% (n = 17) of mothers, 64% (n = 7) of fathers, and 71% (n = 10) of adolescents reported at least one benefit of participating. Eleven percent (n = 2) of mothers, 36% (n = 4) of fathers, and 29% (n = 4) of adolescents said they were not affected; none of the participants reported a negative effect. CONCLUSION: Consistent with prior literature, our study suggests behavioral reproductive research prior to cancer treatment can offer direct benefits to participants and society, without increasing burden. These findings will inform future interventions to improve long-term psychosocial and reproductive outcomes for youth with cancer.

Fertility Preservation for a Teenager with Differences (Disorders) of Sex Development: An Ethics Case Study.

Fertility preservation has become more common for various populations, including oncology patients, transgender individuals, and women who are concerned about age-related infertility. Little attention has been paid to fertility preservation for patients with differences/disorders of sex development (DSD). Our goal in this article is to address specific ethical considerations that are unique to this patient population. To this end, we present a hypothetical DSD case. We then explore ethical considerations related to patient's age, risk of cancer, concern about genetic transmission of a DSD condition to children, co-occurring gender dysphoria, and access to experimental fertility preservation procedures. Given the limitations of current technologies, we recommend offering fertility preservation to individuals living with DSD using an informed decision-making approach that instills realistic expectations and minimizes the potential for false hope. Finally, we conclude with practical recommendations for this case based on the ethical considerations.

Adolescents and Body Modification for Gender Identity Expression.

As a matter of ethics and law, adults enjoy wide berth in securing hormonal and surgical interventions to align their bodies with their desired gender appearance. In contrast, the exercise of choice by minors is more constrained, because they can be less well situated to grasp the nature and consequences of interventions having life-long effects. Even so, some minors hope for body modifications prior to adulthood. Starting very young, some minors may assert atypical gender identity: those with female-typical bodies assert a male identity and those with male-typical bodies assert a female identity. This assertion of identity is atypical only in a descriptive sense, because it is uncharacteristic, not because it is normatively unacceptable. Not all minors persist in their atypical gender identities, but some do. For those who do, it is desirable to minimize unwanted secondary sex characteristics and to maximize desired secondary sex characteristics. I outline here a theory of respect for decisions by minors in regard to hormonal and surgical interventions that help align their bodies with their gender identity. Of particular ethical interest here are body modifications for fertility preservation since certain interventions in the body can leave people unable to have genetically related children. In general, I will show that the degree of respect owed to minors in regard to body modifications for gender identity expression should be scaled according to their decision-making capacities, in the context of robust practices of informed consent.

Is egg freezing a good response to socioeconomic and cultural factors that lead women to postpone motherhood?

In western societies, a growing number of women are currently turning to social egg freezing, a technique that makes it possible to freeze oocytes and thus preserve female reproductive possibilities. The current ethical debate has focused on normative aspects concerning the question of whether social egg freezing empowers women's reproductive autonomy. Due to this narrow focus on autonomy, deeper questions concerning the socio-economic conditions and cultural factors that lead women to delay reproduction, to feel pressured by their biological clock, and thus to consider social egg freezing have not yet received sufficient attention and analysis. The aim of this study was to broaden the ethical debate by focusing on whether social egg freezing is a good response to the socioeconomic and cultural constraints that lead women to postpone motherhood, and therefore whether it can be seen as a means of achieving what in virtue ethics is known as a 'good life'. I will argue that while social egg freezing can be seen as a means to empower women to adapt to current socioeconomic constraints, it is not an adequate response to cultural factors, as these cannot be solved by simply extending a woman's fertility.

Intrafamilial oocyte donation in classic galactosemia: ethical and societal aspects.

Classic galactosemia is a rare inherited disorder of galactose metabolism. Primary ovarian insufficiency (POI) with subfertility affects > 80% of female patients and is an important concern for patients and their parents. Healthcare providers are often consulted for subfertility treatment possibilities. An option brought up by the families is intrafamilial oocyte donation (mother-to-daughter or sister-to-sister). In addition to POI, galactosemia patients can also present varying cognitive and neurological impairments, which may not be fully clear at the time when mother-to-daughter oocyte donation is considered. Ethical and societal aspects arise when exploring this option. This study aimed to provide guidance in aspects to consider based on the views of different groups involved in the oocyte donation process. A qualitative study using in-depth semi-structured interviews with > 50 participants (patients, family members, and healthcare providers) was conducted. From these interviews, themes of concern emerged, which are illustrated and reviewed: (1) family relations, (2) medical impact, (3) patients' cognitive level, (4) agreements to be made in advance and organization of counseling, (5) disclosure to the child, and (6) need for follow-up. We conclude that discussing and carrying out intrafamilial oocyte donation in galactosemia patients requires carefully addressing these themes. This study adds value to the already existing recommendations on intrafamilial oocyte donation in general, since it highlights important additional aspects from the perspectives of patients and their families.

Ethics of fertility preservation for prepubertal children: should clinicians offer procedures where efficacy is largely unproven?

Young children with cancer are treated with interventions that can have a high risk of compromising their reproductive potential. 'Fertility preservation' for children who have not yet reached puberty involves surgically removing and cryopreserving reproductive tissue prior to treatment in the expectation that strategies for the use of this tissue will be developed in the future. Fertility preservation for prepubertal children is ethically complex because the techniques largely lack proven efficacy for this age group. There is professional difference of opinion about whether it is ethical to offer such 'experimental' procedures. The question addressed in this paper is: when, if ever, is it ethically justifiable to offer fertility preservation surgery to prepubertal children? We present the ethical concerns about prepubertal fertility preservation, drawing both on existing literature and our experience discussing this issue with clinicians in clinical ethics case consultations. We argue that offering the procedure is ethically justifiable in certain circumstances. For many children, the balance of benefits and burdens is such that the procedure is ethically permissible but not ethically required; when the procedure is medically safe, it is the parents' decision to make, with appropriate information and guidance from the treating clinicians. We suggest that clinical ethics support processes are necessary to assist clinicians to engage with the ethical complexity of prepubertal fertility preservation and describe the framework that has been integrated into the pathway of care for patients and families attending the Royal Children's Hospital in Melbourne, Australia.

Familial Discordance Regarding Fertility Preservation for a Transgender Teen: An Ethical Case Study.

A 16-year-old adolescent who identifies as transgender wishes to consider fertility preservation prior to the use of gender-affirming hormones. The adolescent's parents are divorced, and one parent supports fertility preservation while the other does not. This case explores the minor's future reproductive autonomy and parental decision making in a field where there is limited evidence of known harms and benefits to the use of fertility preservation in the transgender population and about future potential regret from lack of consideration of fertility preservation during the prime window of opportunity. This case is created from a composite of cases seen at multiple institutions.

Debating social egg freezing: arguments from phases of life.

So-called "social egg freezing" allows a woman to retain the possibility of trying to have a child with her own oocytes later in life, even after having become infertile in the strict sense of the word (that is, infertile without assistance in reproduction).There is a debate about whether it is morally permissible at all, the extent to which it should be permitted legally or even supported, and whether it is ethically desirable. This paper contributes some thoughts to the issue of ethical desirability. More precisely it deals with the question of whether there is any valuable argument to be made on the basis of the idea of life phases and normative expectations related to them. So the question is: Is there a right time in life to have a child, and does this speak against or in favor of social freezing? This question is answered in three steps. First, I will give an overview of ethical arguments that are mostly put forward in favor or against the use of social egg freezing and show that and why the question of life phases should be taken into account. Second, I will sketch what I understand by phases of life, more precisely, what I understand by normatively conceptualized life stages, that are to be distinguished from other kinds of life phases, and how they relate to a good life. Third, I will present two arguments that rely on the idea of life stages and speak against social egg freezing. However, I will criticize them and instead show that from the perspective of life stages nothing speaks against using the technique within certain limits.

Let us talk about eggs! Professional resistance to elective egg vitrification and gendered medical paternalism.

In this paper, by applying a feminist bioethical perspective, we identify a new form of medical paternalism that still shapes contemporary legal policies on human egg cryopreservation performed without medical reasons. The fear of negligent, careless women who opt to delay their pregnancy for mere convenience is a widely known gender biased stereotype. Nevertheless, the opinions and judgments of medical professionals on this issue have not yet been sufficiently explored by in-depth research. In this essay, therefore, first we look at the broader bioethical, legal, and social aspects of human egg cryopreservation. In the second part of the paper we discuss a unique qualitative study conducted with professionals working at Hungarian IVF clinics. We argue, based on a bioethical analysis of the collected data, that when new reproduction technologies provide opportunities for women to widen their range of reproductive choices, the traditional forms of medical paternalism can be reinforced by gendered paternalism, as well. We identify several elements of gendered paternalism that characterized the attitudes of the IVF staff and discuss the professionals' resistance to elective egg freezing and vitrification of eggs for the future. We conclude by suggesting directions for future policy. Although we focus on the Hungarian case in this paper, we are aware that similar attitudes can be observed in some other countries where this technology has become available and requested by women, but where they also face difficulties in their access to it.

About time: how time influences and facilitates patient autonomy in the clinical encounter.

In this article I discuss the little examined relationship between time and patient autonomy. Using the findings from a study on the experience of premenopausal cancer patients making fertility preservation decisions during their treatment, I focus on how the patients in the study understood time, and how this understanding interacted with and influenced their decision-making. I then analyse in more depth the importance of time in patient decision-making, and the relationship of time to concepts of patient autonomy and decision-making in the field of bioethics more generally. Focusing on the relational conception of autonomy, I conclude that time is an integral part of patient autonomy which warrants further research, such that it can be better integrated into concepts of patient autonomy, and the policy and guidelines that they inform and influence.

Oncofertility: Fertile Ground for Conflict Between Patient Autonomy and Medical Values.

Oncofertility is a unique, multidisciplinary field that serves to bridge the gap between available fertility resources and the special reproductive needs of cancer patients. Oncofertility is a growing field due to the increasing number of survivors, development of new oncologic therapies, extension of duration of therapies, and development and refinement of reproductive therapies. While the technologies and demand for services expand, clinicians need to be appropriately prepared for dealing with various clinical scenarios that may require ethical deliberation. Three real cases are presented in which the patient wishes to pursue reproductive assistance, but her decision is met with hesitance or uncertainty by her care team. Discussion of these clinical scenarios highlights ethical implications of oncofertility practice and serves to highlight the need for the establishment of multidisciplinary care teams and guidelines to support both clinicians and patients. IMPLICATIONS FOR PRACTICE: The growing field of oncofertility is ripe for conflict between patient autonomy and medical values due to the nature of cancer and associated threat on an individual's health and survival, as well as the personal significance of childbearing. Cases are presented and ethical implications are discussed to further explore the inherent difficulties in oncofertility practice and guide clinicians in similar situations. Developing guidelines and establishing multidisciplinary teams to facilitate oncofertility discussions and care, as well as training of clinical team members, may improve patient safety, well-being, and satisfaction within the context of fertility decision making, care, and outcomes.