Medical research and reproductive medicine in an ethical context: a critical commentary on the paper dealing with uterine lavage published by Munné et al.

A recent study published in Human Reproduction claimed that uterine lavage offers a non-surgical, minimally invasive strategy for the recovery of human embryos from fertile women who do not want or need IVF for medical reasons but who desire preimplantation genetic testing (PGT) for embryos. To prove this hypothesis, the researchers recruited dozens of young Mexican women. The prospective oocyte donors underwent ovarian stimulation to induce the production of multiple mature oocytes. Subsequently, these women were inseminated by donor semen. A few days later, the developing embryos were collected by uterine lavage (uterine flushing) and subjected to genetic testing for aneuploidies (PGT-A). Oocyte donors with persistently elevated hCG levels, indicating the implantation of one or more embryos after uterine lavage, had to undergo uterine curettage and/or treatment with methotrexate. A critical opinion paper discussing the aforementioned study was published by De Santis and colleagues and has raised critical issues that are largely technical in nature. However, this opinion paper neglects-from our point of view-critical issues of the Mexican study regarding ethical principles and moral standards in human research. These aspects are summarized below.

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.

The medical and ethical challenges of fertility preservation in teenage girls: a case series of sickle cell anaemia patients prior to bone marrow transplant.

Cryopreservation of oocytes has been proposed as a way of storing gametes in young patients at high risk of infertility and premature ovarian failure. Recent advances in cryobiology have yielded promising results, leading to oocyte cryopreservation becoming a mainstay of fertility preservation. In this case series, we describe the feasibility of performing ovarian stimulation, and the ethical challenges faced, in teenage girls, aged 14-18 years, prior to undergoing bone marrow transplant for sickle cell anaemia. All eight consecutive cases completed ovarian stimulation and oocyte retrieval with mature oocytes being found and cryopreserved for each patient. The mean dose of gonadotrophin stimulation was 2134.38 IU (95% CI 1593.34-2675.4) and the mean duration of treatment was 11 days (95% CI 10.02-11.98). The mean number of oocytes retrieved was 14.88 (95% CI 7.39-22.36), of which a mean of 12.13 (95% CI 4.72-19.54) oocytes were mature and cryopreserved. There was one case of moderate ovarian hyperstimulation syndrome that required hospital admission for supportive treatment. Oocyte cryopreservation is a technique that can be successfully employed after the retrieval of mature oocytes from the peripubertal ovary, restoring hope to these patients, and their families, of having their own genetic children in the future.

Treatment and preservation at the extremes of reproductive age: a case report outlining the ethical dilemmas.

PURPOSE: The purpose of the study was to report a livebirth from a cryopreserved embryo created from autologous oocytes collected at 47 years and 9 months that outlines the ethical difficulties of decision-making at the extreme of reproductive age. METHODS: The method used was IVF and embryo cryopreservation within an assisted conception unit prior to adjuvant cancer treatment in a nulliparous patient diagnosed with breast carcinoma (47 years and 9 months at oocyte collection). RESULTS: A 47-year-old nulliparous woman was diagnosed with breast malignancy during work-up for fertility treatment. Ovarian stimulation yielded one embryo from four oocytes that was cryopreserved to allow completion of adjuvant treatment. Subsequent embryo transfer cycle led to a live birth of a healthy baby girl at term, weighing 3.37 kg. CONCLUSION: This paper demonstrates the oldest reported age of autologous oocyte collection to have achieved a livebirth. In women where most would consider treatment futile, we highlight the difficulties in decision-making in this group of patients.

Responding to Requests for Assisted Reproductive Technology Intervention Involving Women Who Cannot Give Consent.

One of the plots of the Canadian science fiction thriller Orphan Black involves a scheme to create dozens of siblings by harvesting the eggs of one woman, fertilizing them with the sperm of a single man, and implanting them for gestation in dozens of apparently willing surrogates.¹ The casualness of the procedure speaks to how comfortable we have all become with reproduction by technology. Yet there are still aspects of this process that remain outside the normative boundaries of most of our worldviews. This article considers recent advances in assisted reproductive technology (ART) that can result in a viable, fertilized embryo even when the mother is herself either permanently unconscious from a severe injury or has actually lost all brain function and therefore meets the legal criteria for brain death. It reviews these advances and applies them to four scenarios, or vignettes, that represent different concerns about the prospective mother's intent to reproduce before losing her ability to give consent.

A survey on the intentions and attitudes towards oocyte cryopreservation for non-medical reasons among women of reproductive age.

BACKGROUND: Although cryopreservation of semen is a routine procedure for preserving male gametes, an efficient method of preserving fertility through oocyte freezing has only recently become available for women. In view of the limited female reproductive lifespan, oocyte freezing can now offer women some protection against the decline in fertility with aging. METHODS: A survey was performed in Belgium among 1914 women of reproductive age (21-40 years) to assess public attitudes towards the phenomenon called 'social oocyte freezing'. Women were questioned on their awareness of the age-related fertility decline and their views and intentions towards considering undergoing oocyte cryopreservation. RESULTS: The electronic questionnaire was completed by 1049 women, giving a response rate of 55%, and 25 were excluded as they were incomplete/inconsistent. Our results demonstrate that 31.5% of respondents consider themselves as potential social oocyte freezers, of which 3.1% would definitely consider the procedure. Just over half of the women (51.8%) would not consider the procedure while 16.7% indicated they had no opinion. Potential oocyte freezers are characterized by a higher number of desired children and more openness to oocyte donation. The decision to actually embark on such treatment would primarily depend on conditions, such as the procedure not affecting their natural fertility and the health of future children. CONCLUSIONS: We conclude that a significant proportion of young women would consider safeguarding their reproductive potential or are at least open to the idea of social oocyte freezing.

Discordant views of experts and laypersons on the adoption of new fertility technology.

BACKGROUND: Healthcare costs are increased by the adoption of novel technologies before solid evidence on efficacy and risks. Oocyte cryopreservation for preserving fertility raises special ethical challenges. We compared opinions of professionals for assisted reproductive technology (ART), bioethicists, medical students and the general population toward the questions: do you support access to oocyte cryopreservation to preserve fertility for personal reasons and who should bear the costs? METHODS: The surveys conducted for this study were carried out in Israel included the following: (1) survey of 21 ART unit directors; (2) interviews with 23 bioethics experts; (3) survey of 196 medical students from 2 universities; (4) random digit-dial population-based survey of the public (N=600). RESULTS: Nearly 80% of ART and bioethics experts and 56% of students thought that oocyte cryopreservation should be allowed even for personal reasons. While expressing concerns about social consequences, bioethicists emphasized individuals' rights. In contrast, among the public, only 40% supported the use of this technology for personal reasons (ranging from 24% among Ultra-orthodox Jews and Arabs, to 51% among seculars or with academic education). Of note, 15% were undecided (vs. <2% among students, P<0.001). Most experts suggested private financing of the procedure for personal reasons, whereas the public preferred national or private insurance coverage. CONCLUSIONS: Nonexperts present a greater level of ambivalence than experts toward the use of a novel fertility technology for nonmedical reasons. Experts' preferences and interests may facilitate adoption of novel technologies with yet unclear effectiveness and safety, potentially contributing to increased healthcare costs.

Egg freezing: a breakthrough for reproductive autonomy?

This article describes the relatively new technology of freezing human eggs and examines whether egg freezing, specifically when it is used by healthy women as 'insurance' against age-related infertility, is a legitimate exercise of reproductive autonomy. Although egg freezing has the potential to expand women's reproductive options and thus may represent a breakthrough for reproductive autonomy, I argue that without adequate information about likely outcomes and risks, women may be choosing to freeze their eggs in a commercially exploitative context, thus undermining rather than expanding reproductive autonomy.

In favour of freezing eggs for non-medical reasons.

This article explores the social benefits and moral arguments in favour of women and couples freezing eggs and embryos for social reasons. Social IVF promotes equal participation by women in employment; it offers women more time to choose a partner; it provides better opportunities for the child as it allows couples more time to become financially stable; it may reduce the risk of genetic and chromosomal abnormality; it allows women and couples to have another child if circumstances change; it offers an option to women and children at risk of ovarian failure; it may increase the egg and embryo pool. There are strong arguments based on equal concern and respect for women which require that women have access to this new technology. Freezing eggs also avoids some of the moral objections associated with freezing embryos.

Posthumous retrieval and use of gametes or embryos: an Ethics Committee opinion.

Posthumous gamete (sperm or oocyte) retrieval or use for reproductive purposes is ethically justifiable if written documentation from the deceased authorizing the procedure is available. Retrieval of sperm or eggs does not commit a center to their later use for reproduction, but may be permissible under the circumstances outlined in this opinion. Embryo use is also justifiable with such documentation. In the absence of written documentation from the decedent, programs open to considering requests for posthumous use of embryos or gametes should only do so when such requests are initiated by the surviving spouse or partner. This document replaces the report of the same name, last published in 2012.

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.

Evidence of Biased Advertising in the Case of Social Egg Freezing.

Oocyte cryopreservation, or 'egg freezing,' is the practice of preserving unfertilised oocytes for later fertilisation. This practice allows women to extend their reproductive years. In 2014, Facebook and Apple announced that they would subsidise their female employees' elective - or 'social' - use of egg freezing so that these women can more easily reconcile the demands of career and family life. This announcement engendered controversy and moral debate. Given that social egg freezing (SEF) is becoming more popular, ethical and empirical analyses are warranted. Here, I utilise content analysis to examine media messages in advertising for SEF. I conclude that many fertility clinics engage in biased advertising - i.e. they advertise the service persuasively, not informatively, emphasising indirect benefits while minimising risks and the low chance of successfully bringing a child to term. As advertising for medical services has been shown to influence the use of those services, advertising for SEF should emphasise clear and easily interpretable statistics about success rate, usage rate, cost, and risk.