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Assisted reproduction often involves biological contributions by third parties such as egg/sperm donors, mitochondrial DNA donors, and surrogate mothers. However, these arrangements are also characterised by a biological relationship between the child and at least one intending parent. For example, one or both intending parents might use their own eggs/sperm in surrogacy, or an intending mother might conceive using donor sperm or gestate a donor embryo. What happens when this relationship is absent, as in the case of 'double‐donor surrogacy' arrangements (DDS)? Here, a child is conceived using both donor eggs and sperm, carried by a surrogate, and raised by the commissioning parents. In this paper, I critically examine proposals to allow DDS in the United Kingdom, and the intentionalist justification for treating this practice distinctly (morally and legally speaking) from private adoption. I argue that the intentionalist approach cannot plausibly justify such a distinction and that other approaches to moral parenthood are also unlikely to succeed. [ABSTRACT FROM AUTHOR]

Human uterus transplantation (UTx)—the most radical and experimental of all current forms of assisted reproduction—gives rise to a range of complex ethical questions, including those related to individual safety, risk, and informed consent. I have argued elsewhere that the wider social impacts and implications of UTx provision must form part of a comprehensive ethical analysis. My socio‐moral critique of UTx provision has been responded to with a number of defences of possible public funding of UTx. In this paper I examine a select number of those defences. These include: that UTx provision would address harms and needs that already exist and as such have priority; that UTx provision is fully compatible with the needed reform of the procreative context in which it would be offered; that UTx provision would not necessarily involve legitimation or endorsement of what are widely agreed to be problematic pronatalist or geneticist norms; and that UTx provision is required as a matter of justice and consistency with other practices. Importantly, defenders are not proposing a ceteris paribus justification of UTx provision; nor do my responses to their arguments represent a comprehensive opposition to UTx. Rather, my more limited purpose here is to show that whatever other defences may be given of publicly funded UTx provision, those considered here do not ultimately succeed and therefore do not allay the concerns underpinning the original socio‐moral critique. [ABSTRACT FROM AUTHOR]

In this paper I argue that some human reproductive genome editing interventions can be therapeutic in nature, and thus that it is false that all such interventions just create healthy individuals. I do this by showing that the conditions established by a therapy definition are met by certain reproductive genome editing interventions. I then defend this position against two objections: (a) reproductive genome editing interventions do not attain one of the two conditions for something to be a therapy, and (b) some reproductive genome editing interventions are therapeutic but in a nonstandard way. In the Conclusion I call for a more nuanced discussion of the nature of reproductive genome editing interventions. [ABSTRACT FROM AUTHOR]

CRISPR is widely considered to be a disruptive technology. However, when it comes to the most controversial topic, germline genome editing (GGE), there is no consensus on whether this technology has any substantial advantages over existing procedures such as embryo selection after in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD). Answering this question, however, is crucial for evaluating whether the pursuit of further research and development on GGE is justified. This paper explores the question from both a clinical and a moral viewpoint, namely whether GGE has any advantages over existing technologies of selective reproduction and whether GGE could complement or even replace them. In a first step, I review an argument of extended applicability. The paper confirms that there are some scenarios in which only germline intervention allows couples to have (biologically related) healthy offspring, because selection will not avoid disease. In a second step, I examine possible moral arguments in favour of genetic modification, namely that GGE could save some embryos and that GGE would provide certain benefits for a future person that PGD does not. Both arguments for GGE have limitations. With regard to the extended applicability of GGE, however, a weak case in favour of GGE should still be made. [ABSTRACT FROM AUTHOR]

In this paper I argue that current law and policy governing germline genetic modification are overly broad and in fact prohibit medical interventions normally considered unobjectionable. The root of the problem lies in the fact law and policy tend to espouse a near categorical ban on medical interventions that alter germline DNA. However, if we pay close attention to the biological mechanisms at play we see that many standard medical interventions result in alterations to DNA that can be transmitted to future generations. The correct focus of policy and regulation thus ought to be determining which kinds of transmissible genetic modifications ought to be permitted, and not whether they should be permitted at all. Given that the scientific classification of biological structures involved in the inheritance of traits is unlikely to be in itself ethically significant, ethicists ought to develop a definition of 'gene' fit for ethical purposes. [ABSTRACT FROM AUTHOR]

The birth of the world's first genetically edited babies in 2018 provoked considerable ethical outrage. Nonetheless, many scientists and bioethicists now advocate the pursuit of clinical uses of human germline gene editing. Progress towards this goal will require research, including clinical trials where genetically edited embryos are implanted into a woman's uterus, gestated, and brought to term. This paper argues that such trials would likely conflict with the fundamental research ethical requirement of non‐exploitation. This is because they would expose people who are in a vulnerable situation to risks and burdens that are substantial and not obviously offset by compensating benefits. I consider how the potential for exploitation in such trials might be mitigated, arguing that a feasible and justifiable approach is not easily found. If this analysis is correct, there is a significant ethical obstacle on the path towards clinical use of human germline gene editing. [ABSTRACT FROM AUTHOR]

This paper urges reconsideration of analyses of the alternatives to reproductive uterus transplantation (UTx). I focus here specifically on the adoption alternative. Importantly, my purpose is not to oppose UTx provision. Rather, it is to propose ways in which ethical analysis and provision of UTx can potentially accommodate the concerns discussed here. I argue that the adoption alternative to UTx is too readily dismissed, and that this is a dismissal with significant moral costs. I suggest that the radical nature of UTx as a form of assisted reproduction calls for an equivalently radical socio‐moral agenda for reform and transformation of adoption law, policy and practice, as well as of the norms that prevail within our presently strongly bio‐normative reproductive context. In doing so I widen the ethical frame of responsible provision of assisted reproduction to encompass not just obligations towards donors and recipient, but also our broader social responsibilities to ensure that we are doing our best to meet the significant needs of some of the most vulnerable members of our society. [ABSTRACT FROM AUTHOR]

Obesity is associated with a reduction in fertility treatment success and increased risks to mother and child. Therefore guidelines of the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) suggest that a body mass index exceeding 35 kg/m2 should be an absolute contraindication to assisted fertility treatment such as in vitro fertilisation IVF. In this paper we challenge the ethical and scientific basis for such a ban. Livebirth rates for severely obese women are reduced by up to 30%, but this result is still far better than that observed for many older women who are allowed access to IVF. This prohibition is particularly unjust when IVF is the only treatment capable of producing a pregnancy, such as bilateral tubal blockage or severe male factor infertility. Furthermore, the absolute magnitude of risks to mother or child is relatively small, and while a woman has a right to be educated about these risks, she alone should be allowed to make a decision on proceeding with treatment. We do not prohibit adults from engaging in dangerous sports, nor do we force parents to vaccinate their children, despite the risks. Similarly, we should not prohibit obese women from becoming parents because of increased risk to themselves or their child. Finally, prohibiting obese women's access to IVF to prevent potential harms such as 'fetal programing' is questionable, especially when compared to that child never being born at all. As such, we believe the RANZCOG ban on severely obese women's access to assisted reproductive treatment is unwarranted and should be revised. [ABSTRACT FROM AUTHOR]

The moral acceptability of anonymous gamete donation remains contested. Although the view that the value of parent–child relationships should not depend on genetic ties is "nearly axiomatic" among philosophers and bioethicists, one well‐known dissenter remains: David Velleman. I argue that most rebuttals to Velleman have simply talked past him because they have failed to understand his fundamental point—that donor conception is a violation of human dignity and as such is wrong even if it does not harm individuals. I challenge Velleman on his own terms by endorsing his metaphysical picture before showing that donor conception is not necessarily a violation of human dignity. I show this by arguing that gamete donation is held to a double standard of self‐knowledge. I develop an account of the self that recognizes that certain kinds of challenges to one's flourishing can contribute to an individual's strength and self‐knowledge. I defend my view against objections that genetic knowledge is categorically different from other ways of knowing oneself and I show that donor conception can respect human dignity as long as it meets certain conditions. [ABSTRACT FROM AUTHOR]

In a recent article in this journal, Alex Mullock, Elizabeth Chloe Romanis and Dunja Begović provide an analysis of gestational surrogacy and uterus transplantation (UTx) from the perspective of those who may decide to act as gestational surrogates and womb donors, referred to as 'womb‐givers'. In this article, I advance two sets of claims aimed at critically engaging with some aspects of their analysis. Firstly, I argue that the expression 'womb‐givers' obscures the biologically, socially and politically salient issue that those who engage in these practices are primarily persons and women. My contention is that this is of substance in discussions of the burdens and benefits of gestational surrogacy and UTx, which need to consider the specific position that women occupy in society, and the hierarchies that mediate their lives, experiences and preferences. Second, I argue that, if one were to take seriously the experiences and preferences of the women who may engage in these practices, and their bodily autonomy, then gestational surrogacy and UTx should be regarded as biologically and sociopolitically incommensurable. Mullock et al. overlook important aspects of gestational surrogacy, such as the embodied nature of pregnancy and childbirth, the sociopolitical significance of these experiences, and the often‐oppressive social norms that shape them. Whilst biology is not destiny, I suggest that it is socially and politically 'sticky' when it comes to this significance and norms, especially within the sphere of reproduction. Towards the end of the article, I query the authors' conceptualisation of bodily autonomy and of the instruments that enable its respect and promotion. [ABSTRACT FROM AUTHOR]

Establishing the nature of genetic parenthood is an important task. This is, firstly, because many people desire that relationship and it is in their interest to know what that is, and secondly, because there is a view that it may incur certain moral obligations between the genetic parent and their child. Many theorists have made attempts to define exactly what genetic parenthood is. I show that these definitions are deficient if they wish to fully capture all reproductive scenarios in ways that are intuitive and/or meaningful. Through a series of cases involving technologies such as cloning and genome editing, we see that in lieu of the traditional two parents, there are possible beings who have no genetic parents, one genetic parent, or many genetic parents. Establishing these cases complicates our understanding of genetic parenthood. From this, we must reconsider current definitions, as well as the usefulness of defining genetic parenthood in these complex cases. Here I do not aim to establish a new definition, but rather to suggest that this complexity makes it necessary to re‐assess the importance of the connection between genetic parenthood and parental obligations and authorities. [ABSTRACT FROM AUTHOR]

Infertility is an unpredictable but widespread condition. While high-income countries grapple with when, or how to cover the costs of assisted reproductive technology (ART), such as in-vitro fertilisation (IVF), these services are generally only available to wealthy persons at private facilities in low- and middle-income countries (LMICs). Although the principle of non-interference with normal individual reproductive rights is robust, whether it is also the responsibility of collective society to provide the means (when ART applies) to achieve pregnancy, is controversial. Recently, a low-cost model was developed at a South African public institution. The target population for this model was "helpless and marginalised, childless couples", but a new threat has arisen, namely, infertile couples who could conceivably afford private care. In the allocation of this scarce resource, we argue for a prioritarian response that first addresses the worst-off, in order to even out unequal access imposed by sharp differences in income. [ABSTRACT FROM AUTHOR]

Objective: To assess academic performance in singletons aged 15–16 years conceived after frozen embryo transfer (FET) compared with singletons born after fresh embryo transfer (ET) in Danish cohorts born from 1995 to 2001. Design: Danish national registry‐based cohort study. Setting: Danish national registries. Population: All 6495 singletons conceived after assisted reproductive technology (ART) treatment in Denmark from 1995 to 2001 [FET (n) = 423; fresh ET (n) = 6072]. Methods: Mean test scores on a national standardised and international comparable grading‐scale. Comparisons of test score were first made in univariate analysis (Model 1) and secondly in a multivariate linear model (Model 2) adjusting for relevant reproductive and socio‐demographic covariates such as the occupational and educational level of the parents. Sensitivity analyses on FET‐IVF (in vitro fertilisation) versus fresh ET‐IVF and FET‐ICSI (intracytoplasmic sperm injection) versus fresh ET‐ICSI were made. Linear mixed models were used to account for the correlation in test scores of siblings for continuous outcome. Main outcome measures: Mean overall test score and test score in Danish, mathematics, English, and physics/chemistry. Results: Crude and adjusted mean test scores were similar for adolescents conceived after FET compared with fresh ET. The crude mean difference was +0.11 (95% CI −0.11; 0.34), and the adjusted mean difference was +0.12 (95% CI −0.09; 0.34). Conclusions: Adolescents conceived after FET had similar academic performance at 15–16 of years of age compared with children conceived after fresh ET. Using frozen embryos in fertility treatment does not affect school performance in Danish adolescents aged 15–16 years. Using frozen embryos in ART treatment does not affect school performance in Danish adolescents aged 15–16 years. [ABSTRACT FROM AUTHOR]

Background: Assisted reproductive techniques are associated with an increased risk of adverse pregnancy outcomes, including low birthweight and intrauterine growth restriction. Yet, the long-term follow-up on the growth of these children is limited.Objective: To systematically review the literature on post-neonatal height and weight among children conceived following in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment, compared with that of children born after spontaneous conception.Search Strategy: A systematic computerised literature search using the online databases PubMed, Embase, and Scopus.Selection Criteria: Cohort or case-control studies with an exposed group of singletons conceived following IVF or ICSI along with a control group of spontaneously conceived singletons.Data Collection and Analysis: Studies were reviewed by at least two authors. Meta-analyses were conducted using Cochrane Review Manager. The quality of the studies was assessed with the Newcastle-Ottawa Scale.Main Results: Twenty studies were included, with 13 of these eligible for meta-analyses. The meta-analyses compared 3972 children born after IVF/ICSI with 11 012 spontaneously conceived children and revealed no statistically significant difference in child weight [mean difference (MD) in weight of -160 g; 95% confidence interval (95% CI) -360, 3]. When stratifying by age of child at follow-up, we found a significant lower weight in children aged 0-4 years conceived following IVF/ICSI treatment (MD -180 g; 95% CI -320, -4), but this was no longer significant in children from 5 years of age (MD -160 g; 95% CI -580, 260). The pooled analysis revealed no statistically significant difference in childhood height.Conclusions: In vitro fertilisation/ICSI was not associated with long-term weight and height.Tweetable Abstract: Children born following IVF/ICSI do not have impaired long-term weight or height compared with spontaneously conceived children. [ABSTRACT FROM AUTHOR]

Abstract: It has been more than 15 years since the measurement of serum anti‐Müllerian hormone (AMH) first allowed the quantitative assessment of ovarian reserve. Meanwhile, the clinical implication of serum AMH has been expanding. The measurement of serum AMH has been applied in various clinical fields, including assisted reproduction, menopause, reproductive disorders and assessment of ovarian damage/toxicity. Well‐known findings about the usefulness of serum AMH revealed by numerous studies executed in the early era include decline with aging, a good correlation with oocyte yield in assisted reproduction, upregulation in polycystic ovarian syndrome and a decrease on ovarian surgery and toxic treatment. More intensive research, including a meta‐analysis, cutting‐edge clinical trial and advances in AMH assays, has yielded newer findings and firmer clinical interpretations in serum AMH in the past few years. Variations in the AMH decline trajectory in the general population do not support the accurate prediction of menopause. The ability to predict pregnancy in infertility treatment and natural conception is poor, while a nomogram integrating serum AMH as a stimulation protocol is useful for avoiding poor and/or hyper‐responses. On the other hand, improvements in measuring very low concentrations of serum AMH may be capable of distinguishing women with poor ovarian function. Age‐independent standardization of AMH values may be helpful for comparing ovarian reserves among women at different ages. [ABSTRACT FROM AUTHOR]

Objectives: To assess the prevalence of congenital uterine anomalies, including arcuate uterus, and their effect on reproductive outcome in subfertile women undergoing assisted reproduction.Methods: Consecutive women referred for subfertility between May 2009 and November 2015 who underwent assisted reproduction were included in the study. As part of the initial assessment, each woman underwent three-dimensional transvaginal sonography. Uterine morphology was classified using the modified American Fertility Society (AFS) classification of congenital uterine anomalies proposed by Salim et al. If the external contour of the uterus was uniformly convex or had an indentation of < 10 mm, but there was a cavity indentation, it was defined as arcuate or septate. Arcuate uterus was further defined as the presence of a concave fundal indentation with a central point of indentation at an obtuse angle. Subseptate uterus was defined as the presence of a septum, not extending to the cervix, with the central point of the septum at an acute angle; if the septum extended to the internal cervical os, the uterus was defined as septate. Reproductive outcomes, including live birth, clinical pregnancy and preterm birth, were compared between women with a normal uterus and those with a congenital uterine anomaly. Subgroup analysis by type of uterine morphology and logistic regression analysis adjusted for age, body mass index, levels of anti-Müllerian hormone, antral follicle count and number and day of embryo transfer were performed.Results: A total of 2375 women were included in the study, of whom 1943 (81.8%) had a normal uterus and 432 (18.2%) had a congenital uterine anomaly. The most common anomalies were arcuate (n = 387 (16.3%)) and subseptate (n = 16 (0.7%)) uterus. The rate of live birth was similar between women with a uterine anomaly and those with a normal uterus (35% vs 37%; P = 0.47). The rates of clinical pregnancy, mode of delivery and sex of the newborn were also similar between the two groups. Preterm birth before 37 weeks' gestation was more common in women with uterine anomalies than in controls (22% vs 14%, respectively; P = 0.03). Subgroup analysis by type of anomaly showed no difference in the incidence of live birth and clinical pregnancy for women with an arcuate uterus, but indicated worse pregnancy outcome in women with other major anomalies (P = 0.042 and 0.048, respectively).Conclusions: Congenital uterine anomalies as a whole, when defined using the modified AFS classification, do not affect clinical pregnancy or live-birth rates in women following assisted reproduction, but do increase the incidence of preterm birth. The presence of uterine abnormalities more severe than arcuate uterus significantly worsens all pregnancy outcomes. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Introduction: Until recently, limited options for preserving fertility in order to delay childbearing were available. Although egg freezing and successful thawing is now possible, it remains unclear to what extent women are aware of the availability of this technique, their attitudes towards its use, or the circumstances under which this technique may be considered.Material and Methods: An online cross-sectional survey was designed to investigate knowledge and attitudes of women in Denmark and the UK on egg freezing and their potential intentions regarding the procedure.Results: Data was collected from September 2012 to September 2013 and the responses of 973 women were analyzed. In total, 83% of women reported having heard of egg freezing, and nearly all considered it acceptable for medical indications, whilst 89% considered it acceptable for social reasons. Overall, 19% expressed active interest in the procedure, and 27% expressed possible interest. Key factors found to positively influence attitudes to accepting the procedure were reassurance that it would not affect future fertility and greater than 50% chance of achieving a live birth. Characteristics significantly associated with intention to freeze eggs were being single, age under 35 years, childlessness, and a history of infertility. In this group, risk and cost were less important considerations.Conclusions: This study indicates that there is widespread awareness and support of the availability of eggs freezing for reproductive planning. Reassurance regarding its efficacy appears more important than its potential adverse effects on their health or that of future children, or the costs of the procedure. [ABSTRACT FROM AUTHOR]

Epigenetic modification controls gene activity without changes in the DNA sequence. The genome undergoes several phases of epigenetic programming during gametogenesis and early embryo development, coinciding with assisted reproductive technologies (ART) treatments. Imprinting disorders have been associated with ART techniques, but disentangling the influence of the ART procedures per se from the effect of the reproductive disease of the parents is a challenge. Epidemiological human studies have shown altered birthweight profiles in ART compared with spontaneously conceived singletons. Conception with cryopreserved/thawed embryos results in a higher risk of large-for-gestational-age babies, which may be due to epigenetic modification. Further animal studies have shown altered gene expression profiles in offspring conceived by ART related to altered glucose metabolism. It is controversial whether human adolescents conceived by ART have altered lipid and glucose profiles and thereby a higher long-term risk of cardiovascular disease and diabetes. This commentary describes the basic concepts of epigenetics and gives a short overview of the existing literature on the association between imprinting disorders, epigenetic modification and ART. [ABSTRACT FROM AUTHOR]