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.

Counseling, risks, and ethical considerations of planned oocyte cryopreservation.

The use of planned oocyte cryopreservation for nonmedical need has been steadily increasing, especially since the experimental label on this procedure was lifted nearly 10 years ago. With this rise, patients' desires to postpone or conserve their reproductive potential have become increasingly nuanced, and the need for complex individualized counseling has grown. In addition, there are several ethical considerations, including risks, access, and patient comprehension that must be discussed with patients who are considering this procedure. In this review, we provide an in-depth discussion of these concepts, highlighting the need for individualized and comprehensive counseling that recognizes the gaps in knowledge that remains in this somewhat novel domain.

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.

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.

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 for Pediatric and Adolescent Patients With Cancer: Medical and Ethical Considerations.

Many cancers presenting in children and adolescents are curable with surgery, chemotherapy, and/or radiotherapy. Potential adverse consequences of treatment include sterility, infertility, or subfertility as a result of gonad removal, damage to germ cells as a result of adjuvant therapy, or damage to the pituitary and hypothalamus or uterus as a result of irradiation. In recent years, treatment of solid tumors and hematologic malignancies has been modified in an attempt to reduce damage to the gonadal axis. Simultaneously, advances in assisted reproductive technology have led to new possibilities for the prevention and treatment of infertility. This clinical report reviews the medical aspects and ethical considerations that arise when considering fertility preservation in pediatric and adolescent patients with cancer.

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.

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.

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.

[Thoughts on the revision of the bioethics law in the field of assisted reproductive technologies (ART). The end of a conceptual framework?] / Réflexions autour de la révision de la loi bioéthique dans le domaine de l'assistance médicale à la procréation - Une rupture du cadre conceptuel ?

This contribution aims at analysing and presenting a comparative dimension concerning the issues raised for the upcoming French Bioethics law revision in the field of assisted reproductive technologies (ART) : access of female same-sex couples and single women to ART ; the authorization of post-mortem procreation ; enlarging eligibility criteria for oocyte self-conservation ; and lifting the anonymity of gamete donation. These questions touch at the very heart of the French bioethics model conceived in 1994, and their revision would constitute a conceptual upheaval.

A new possibility in fertility preservation: The artificial ovary.

Conventional fertility preservation methods such as oocyte or embryo cryopreservation are currently insufficient to treat including those patients with prepubertal cancer and premature ovarian failure. Ovarian tissue cryopreservation presents as an alternative but has limitations with a potential risk of reintroducing malignant cells in patients who recover from cancer, those of chemotherapy prior to tissue cryopreservation. The so called "artificial ovary" aims to resolve this issue by transplanting isolated follicles with or without a biological scaffold. The artificial ovary may also offer an effective alternative option for those who cannot benefit from traditional assisted reproductive techniques such as in vitro fertilisation. To date, in animal studies and human trial, the artificial ovary restored endocrine function, achieved in vivo follicular development, and resulted in successful pregnancies. However, development of a technique for higher follicular recovery rate and a more optimised design of delivery scaffold, better transplantation techniques to prevent postsurgical ischemia, and consideration for genetic safety are required for safer and consistent human clinical applications. Ideas from different transplantation surgeries (e.g., entire ovary, ovarian cortex, and transplantation with tissue-engineered products) can be applied to enhance the efficacy of artificial ovarian transplantation. For the better application of artificial ovary, a deeper understanding of mechanical and biochemical properties of the ovary and folliculogenesis after cryopreservation, transplantation with or without scaffold, and development of sophisticated in vivo imaging techniques of transplanted artificial ovary need to precede its efficient clinical application.

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.

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.

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.

Chapitre 9. Oncofertilité et jeunes filles prépubères : Un « droit à un avenir ouvert ¼ ?

Chemotherapy and radiotherapy have increased the life expectancy of cancer patients but may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of treatment on future reproductive autonomy are a major concern. While a few options are open to patients post-puberty, the only option currently open to prepubescent girls is cryopreservation of ovarian tissue and subsequent transplantation. Yet, this procedure raises ethical concerns related to its experimental nature and to risks involved in surgery and general anesthesia. In addition, the risk of malignant cells being reintroduced in the future following autologous transplantation of the ovarian tissue is still poorly evaluated. A number of ethical issues arise surrounding this procedure. While the girl's future reproductive autonomy is at stake, it is important to also consider risks associated with the procedure. Fertility preservation through cryopreservation of ovarian tissue thus raises a conflict between the principles of beneficence and non-maleficence. We argue that the ethical complexity surrounding fertility preservation for prepubescent girls should be resolved by applying the principle of "the child's right to an open future". We propose to consider 'beneficence' through the lens of the reproductive autonomy and her potentialin becoming a genetic parent.

[Chapitre 9. Oncofertility and prepubescent girls: A 'right to an open future'?.] / Chapitre 9. Oncofertilité et jeunes filles prépubères : Un « droit à un avenir ouvert ¼ ?

Chemotherapy and radiotherapy have increased the life expectancy of cancer patients but may cause premature ovarian failure and irreversible loss of fertility. In the context of childhood cancers, it is now acknowledged that possible negative effects of treatment on future reproductive autonomy are a major concern. While a few options are open to patients post-puberty, the only option currently open to prepubescent girls is cryopreservation of ovarian tissue and subsequent transplantation. Yet, this procedure raises ethical concerns related to its experimental nature and to risks involved in surgery and general anesthesia. In addition, the risk of malignant cells being reintroduced in the future following autologous transplantation of the ovarian tissue is still poorly evaluated. A number of ethical issues arise surrounding this procedure. While the girl’s future reproductive autonomy is at stake, it is important to also consider risks associated with the procedure. Fertility preservation through cryopreservation of ovarian tissue thus raises a conflict between the principles of beneficence and non-maleficence. We argue that the ethical complexity surrounding fertility preservation for prepubescent girls should be resolved by applying the principle of “the child’s right to an open future”. We propose to consider ‘beneficence’ through the lens of the reproductive autonomy and her potentialin becoming a genetic parent.

Freezing fertility or freezing false hope? A content analysis of social egg freezing in U.S. print media.

In 2012, the American Society for Reproductive Medicine (ASRM) lifted the experimental label on oocyte preservation, but cautioned against women using it to avoid age-related infertility, known as social egg freezing (SEF). In 2014, Facebook and Apple announced that they would offer SEF as a workplace benefit. Within the context of a rapidly growing market for SEF, we were interested in how these two decisions affected media discussions, given that such discourse can strongly influence public perceptions and behaviors. We used a content analysis methodology to code 138 articles published in U.S. newspapers and magazines between 2012 and 2015. Focusing on a financial concern over the cost of SEF and the lack of insurance for SEF, we found that media portrayals of SEF pivot away from the ethical principle of nonmaleficence centered in the ASRM decision to discourage SEF. Instead, they highlight an issue of justice that can be remedied through the offer of SEF as a workplace benefit. Overall, media portrayals of SEF paint a simplistic and rosy picture that more options, especially more reproductive and economic options, automatically enhance women's autonomy.