Abstract In medically assisted reproduction (MAR) success has mostly been measured in terms of achieving (healthy) livebirths. We argue this focus is too narrow and that success should be measured in ...terms of alleviating patient suffering caused by an unfulfilled child wish. The major implication is that clinics must better tailored care to effectively support patients who do not have child(ren) with treatment. First, we argue that clinics have a duty of care towards patients for whom MAR does not result in children because this is a common treatment outcome, because treatment is burdensome and creates new losses for patients, and because the field has the necessary expertise to provide support and it is part of patient-centred care. Then, we examine concerns about the adequacy of addressing the possibility that treatment may end without children, namely, that this may hinder patients’ hope and put them off doing treatment, and that it may be perceived as a sign of clinical incompetence, as well as concerns about the required skill set. We end with a set of research-informed recommendations to promote healthy adjustment to ending fertility treatment without children. These focus on the need to reconceptualize ‘success’ and ‘failure’ in MAR, to promote open discussion about the possibility of treatment not resulting in children and encourage patients to develop ‘plan(s) B’, to support patients who end treatment without children, and to create the organizational structures needed to support clinics and healthcare professionals in this endeavour.
Abstract
Recently, complete in vitro generation of male gametes starting from pluripotent stem cells was obtained in a mouse model with live offspring as a result. This breakthrough was probably due ...to the use of a stepwise differentiation protocol taking the tightly regulated in vivo situation into account. As shown previously, factors of the TGFβ superfamily, metabolites of vitamin A, growth hormones, sex steroids and, most importantly, somatic cell support are major regulators of the development, survival, proliferation and differentiation of male gametes. However, up till now, all differentiation protocols starting from human pluripotent stem cells only focused on one or two of these substantive factors, not taking any timeframe into account, leading to promising but unsatisfying results with low efficiency. Therefore, progress might be achieved by including a stepwise differentiation protocol, including all proven contributing regulators, and therefore mimicking more closely human in vivo spermatogenesis and its temporo-spatial organization. In this review, the indispensable regulators of in vivo spermatogenesis and the outcomes of related human in vitro studies are discussed with the aim of unravelling the most successful combinations of medium factors to be used in future differentiation protocols.
Two leading European professional societies, the European Society of Human Genetics and the European Society for Human Reproduction and Embryology, have worked together since 2004 to evaluate the ...impact of fast research advances at the interface of assisted reproduction and genetics, including their application into clinical practice. In September 2016, the expert panel met for the third time. The topics discussed highlighted important issues covering the impacts of expanded carrier screening, direct-to-consumer genetic testing, voiding of the presumed anonymity of gamete donors by advanced genetic testing, advances in the research of genetic causes underlying male and female infertility, utilisation of massively parallel sequencing in preimplantation genetic testing and non-invasive prenatal screening, mitochondrial replacement in human oocytes, and additionally, issues related to cross-generational epigenetic inheritance following IVF and germline genome editing. The resulting paper represents a consensus of both professional societies involved.
The derivation of gametes from patient-specific pluripotent stem cells may provide new perspectives for genetic parenthood for patients currently facing sterility. We use current data to assess the ...gamete differentiation potential of patient-specific pluripotent stem cells and to determine which reprogramming strategy holds the greatest promise for future clinical applications. First, we compare the two best established somatic cell reprogramming strategies: the production of induced pluripotent stem cells (iPSC) and somatic cell nuclear transfer followed by embryonic stem cell derivation (SCNT-ESC). Recent reports have indicated that these stem cells, though displaying a similar pluripotency potential, show important differences at the epigenomic level, which may have repercussions on their applicability. By comparing data on the genetic and epigenetic stability of these cell types during derivation and in-vitro culture, we assess the reprogramming efficiency of both technologies and possible effects on the subsequent differentiation potential of these cells. Moreover, we discuss possible implications of mitochondrial heteroplasmy. We also address the ethical aspects of both cell types, as well as the safety considerations associated with clinical applications using these cells, e.g. the known genomic instability of human PSCs during long-term culture. Secondly, we discuss the role of the stem cell pluripotency state in germ cell differentiation. In mice, success in germ cell development from pluripotent stem cells could only be achieved when starting from a naive state of pluripotency. It remains to be investigated if the naive state is also crucial for germ cell differentiation in human cells and to what extent human naive pluripotency resembles the naive state in mouse.
Abstract
Study question
What underlying norms and values are the inclusion and exclusion criteria for egg freezing in Belgium and France based on? Are they equitable and fair?
Summary answer
...Exclusion criteria are desirable from a distributive justice viewpoint. While age limits are justifiable, criteria such as oncological vs non-oncological and gender are not equitable.
What is known already
In 2018, the Belgian federal institute for health insurance (RIZIV or ENAMI) decided on health insurance coverage for the retrieval, freezing and storing of gametes and gonadal tissues for fertility preservation. This coverage is however not available to all candidates for egg freezing, but strongly directed towards oncology patients. France took a different approach. Since the French Law on Bioethics was passed in August 2021, egg freezing is available to all women between their 29th and 37th birthday. Egg harvesting is covered by public health insurance, but not the storage costs.
Study design, size, duration
This is a normative analysis in which the different inclusion and exclusion criteria from the Belgian and French system are critically analysed in light of existing ethical scholarship on access to egg freezing from the past decade. Special attention is paid to arguments relating to justice as fairness.
Participants/materials, setting, methods
Literature research; normative analysis
The method that is used to bring empirical data (as found in literature research) and normative ethics together is the ‘Wide Reflective Equilibrium’, the most commonly used method in bioethics.
Main results and the role of chance
While the French system, allowing access to a great range of people, appears to be the most fair, the opportunity costs involved plead for the implementation of inclusion and exclusion criteria to make sure that resources are allocated in a more equitable manner. These criteria should be based on effectiveness and social justice. Looking at the currently implemented criteria, the distinction between medical and non-medical or between oncological and non-oncological conditions is difficult to justify given the large grey area where these categories overlap. For example, in Belgium several categories of people at risk of losing their fertility are excluded: transmen receiving gender-confirming therapy, people needing a stem cell transplant for other than hematopoietic reasons (e.g. sickle cell anaemia) or women nearing the end of their reproductive lifespan (also if due to previous cancer treatment). Arguments in favour of age limits are effectiveness and the avoidance of false hope for people of advanced reproductive age. Arguments against are founded on concerns of ageism and social injustice. Of the potential arguments arguing for gender limits – specifically the exclusion of transmen – none appear convincing, while access for transmen is problematic both in Belgium and France.
Limitations, reasons for caution
This analysis is a case study of two countries, not a comprehensive or representative analysis of European policies.
Wider implications of the findings
Countries that are considering implementing systems for coverage of egg freezing by public funding, can learn from these case studies to better finetune their inclusion and exclusion criteria.
Trial registration number
N/A
The future success of stem cell research by means of somatic cell nuclear transfer (SCNT) depends on a sufficient supply of human oocytes. However, oocyte donation presents certain risks for the ...donor, and concerns for women’s welfare are rightly vocalized. At the same time, these risks are comparable with the risks faced by other healthy research subjects. Thus, research donation can withstand ethical scrutiny if it fulfils the same conditions as other research involving healthy human subjects. Specifically, this means that the benefits of the research project need to outweigh the harms, that risks must be minimized, that informed consent has to be guaranteed by averting undue inducement and the recruitment of vulnerable women and that donors can and should be reimbursed for their research participation.
ABSTRACT
While education about fertility is not intrinsically controversial, finding the right language to communicate the topic can be challenging, as there are several risks of unintended negative ...effects such as dissonance, anxiety, culpability, and stigma due to social norming. In this article, we share some of our learnings from promoting fertility awareness in the hope that they will inspire further debate and research on this topic. Starting from the ethical principles of respect for reproductive autonomy, avoiding harm (in terms of stigma or anxiety) and inclusivity, we have formulated five recommendations: (i) frame fertility awareness messages with (reproductive) autonomy in mind and aim to be inclusive of those who do not represent the traditional nuclear family; (ii) be empathetic and steer clear of blame; (iii) avoid scaremongering and offer a positive angle; (iv) give due consideration to both women and men in fertility health messaging; and (v) tailor the messages to particular contexts and audiences and develop resources in close collaboration with the target groups.
Mycotic aortic aneurysm is a rare and challenging complication of aortic homografts caused by an infection and is associated with high morbidity and mortality.
We report the first case of an aortic ...cross homograft mycotic pseudoaneurysm caused by Robinsoniella peoriensis in a 70-year-old man. Our patient underwent surgery for a recurrence of aortic cross mycotic pseudoaneurysm at the level of the aortic homograft he had had 7 years before. A clot-removal of the pseudoaneurysm was surgically carried out and the homograft was completely removed. Anaerobic culture from tissue samples yielded pure growth of a spore-forming Gram-positive rod, identified later as Robinsoniella peoriensis by 16S rRNA gene sequencing. The patient was then discharged with oral clindamycin according to the in vitro susceptibility testing.
Identification of R. peoriensis might be challenging in clinical laboratories with no access to molecular methods.
Abstract Study question To what extent should new genetic risk information, identified after donation, be disclosed to recipients? Summary answer Withholding new genetic risk information from donor ...sperm recipients may sometimes be ethically justified or even preferred. What is known already In some cases, donor-conceived persons are born with (suspected) harmful genetic mutations. These occurrences may flag increased genetic risks for others if the donor is used for multiple recipients. Genetic conditions can also emerge in donors or their families after donation. Current guidelines, such as those established by the European Directorate for the Quality of Medicines & HealthCare, recommend contacting recipients “in the case of a diagnosis that may seriously affect a child’s health”. However, the specific timing of such disclosures and the circumstances under which (or even whether) information may be withheld are unclear. Study design, size, duration This normative analysis draws initial insights from empirical data obtained from a quantitative study into current practices of fertility clinics and extends to a comprehensive review of academic literature and international guidelines. It evaluates current practices and explores the justifications for (not) informing recipients about (possible) genetic risks linked to their donor, guided by bioethical principles. Participants/materials, setting, methods In June 2023, an electronic questionnaire was sent to all fertility clinics in Belgium to obtain information on current practices regarding the management of genetic mutations in donor treatment. The responses from 15 clinics provided empirical insights that served as an impetus for the subsequent normative analysis. This analysis integrated the findings with normative considerations using the ‘wide reflective equilibrium’ method. Main results and the role of chance Our findings revealed considerable diversity in current practices. Some clinics always informed recipients of newly identified genetic risks (possibly) related to their donor, while others based their decision on various factors. The main arguments for disclosing this information are clinical utility (beneficence) and respect for the recipient’s autonomy. Withholding health-related information can be harmful, especially if it impedes diagnosis and treatment. Moreover, when sperm samples are reserved for additional children from the same donor, disclosure facilitates better-informed reproductive decisions. Conversely, non-disclosure is sometimes justified on the same grounds. If the recurrence risk is absent or equivalent to the general population risk level, disclosure could cause undue alarm and overtreatment. These harms may outweigh the marginal benefits of (immediate) disclosure, particularly for unconfirmed, late-onset, non-severe, and untreatable conditions. Respecting autonomy also implies recognizing the right not to know, by allowing recipients to prespecify the type of information they wish to receive (e.g., untreatable conditions). However, other factors can complicate this assessment. When early diagnosis is crucial, confirming the donor’s link to the reported condition or determining the recurrence risk may take too long. Additionally, a thorough risk analysis becomes more intricate if insemination is planned, embryos are created, or during pregnancy. Limitations, reasons for caution This analysis focuses on cases with anonymous donors and excludes situations involving identifiable and known donors. If the recipient and donor know each other, a distinct set of ethical considerations and duties may emerge. Wider implications of the findings The need for a nuanced, context-sensitive ethical framework for the disclosure of (potential) harmful genetic mutations in a donor to recipients of donor sperm is highlighted. Such a framework could inspire policy development and support ethical decision-making in fertility treatments. Trial registration number Not applicable
Despite the initial reactions of disapproval, more and more fertility clinics are now offering oocyte cryopreservation to healthy women in order to extend their reproductive options. However, ...so-called social freezing is not placed on an equal footing with ‘regular’ IVF treatments where public funding is concerned. In those countries or states where IVF patients receive a number of free cycles, we argue that fertilization and transfer cycles of women who proactively cryopreserved their oocytes should be covered. Moreover, when the argument of justice is consistently applied, coverage should also include the expenses of ovarian stimulation, oocyte retrieval and storage. Different modalities are possible: full coverage from the onset, reimbursement in cash or reimbursement in kind, by offering more free transfer cycles.
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