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In vitro maturation (IVM) of human oocytes is a reproductive technique which has been practiced for 25 years and is gaining popularity. However, the techniques used for IVM differ substantially across clinics and they result in extremely variable pregnancy rates, partially due to some of these differences in protocols. Such differences include the use in some cycles of hCG triggering prior to oocyte retrieval and the use of a few days of gonadotrophin treatment to support moderate follicle growth. Other important factors are patient selection (including those with polycystic ovaries or decreased ovarian reserve), the number of embryos transferred and cleavage-stage embryo or blastocyst transfer. There are also substantial differences of opinion among clinicians regarding IVM and what it implies. Due to the large variation in protocols, a decision was made to write this paper in an attempt to introduce uniformity when comparing treatments and outcomes of IVM. A clinical definition of IVM was developed: The retrieval of oocytes from small and intermediate sized follicles in an ovary before the largest follicle has surpassed 13 mm in mean diameter. The use of short gonadotrophin stimulation should be acknowledged. However, it should be stated that metaphase II oocytes also have the potential to be collected at that time in the cycles associated with either hCG or GnRH agonist priming. Many feel this is not IVM because some mature oocytes are retrieved, therefore, we recommend renaming this procedure either natural cycle IVF or modified natural cycle IVF (if gonadotrophin stimulation is given) with early triggering, combined with IVM The percentage as well as the absolute number of mature oocytes at retrieval should be indicated. The use of these titles will allow transparency when comparing results of IVM cycles. [ABSTRACT FROM AUTHOR]

Over the past half a century many countries have witnessed a rapid fall in total fertility rates, particularly in the world's most advanced economies including the industrial powerhouses of Eastern Asia and Europe. Such nations have now passed through the first and second demographic transitions and are currently exhibiting fertility rates well below the replacement threshold of 2.1, with no sign of recovery. This paper examines the factors responsible for driving these demographic transitions and considers their impact on both fertility and fecundity (our fundamental capacity to reproduce). I argue that because the first demographic transition was extremely rapid and largely driven by socioeconomic factors, it has had no lasting impact on the genetic/epigenetic underpinnings of human fecundity. However, the second demographic transition will be different. A series of conditions associated with low fertility societies, including relaxed selection pressure for high-fertility genotypes, the indiscriminate use of assisted reproductive technologies to treat human infertility, and environmental contamination with reproductive toxicants, may impact our genetic constitution in ways that compromise the future fecundity of our species. Since any fundamental change in the genetic foundations of human reproduction will be difficult to reverse, we should actively pursue methods to monitor human fecundity, as sub-replacement fertility levels become established across the globe. [ABSTRACT FROM AUTHOR]

Procreative obligations are often discussed by evaluating only the consequences of reproductive actions or omissions; less attention is paid to the moral role of intentions and attitudes. In this paper, I assess whether intentions and attitudes can contribute to defining our moral obligations with regard to assisted reproductive technologies already available, such as preimplantation genetic diagnosis (PGD), and those that may be available in future, such as reproductive genome editing and ectogenesis, in a way compatible with person‐affecting constraints. I propose the parent–child relationship argument, which is based on the moral distinction between creating and parenting a child. Hence, I first argue that intentions and attitudes can play a role in defining our moral obligations in reproductive decisions involving PGD. Second, I maintain that if we accept this and recognize reproductive genome editing and ectogenesis as person‐affecting procedures, we should be committed to arguing that prospective parents may have moral reasons to prefer reproduction via such techniques than via sexual intercourse. In both cases, I observe an extension of our procreative responsibility beyond what is proposed by the consequentialist person‐affecting morality. [ABSTRACT FROM AUTHOR]

Background: In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain.Objective and Rationale: This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals.Search Methods: PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on 'SARS-CoV-2' and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible.Outcomes: From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients' performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients.Wider Implications: This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil. [ABSTRACT FROM AUTHOR]

For females without a functioning womb, the only way to become a biological parent is via assisted gestation—either surrogacy or uterus transplantation (UTx). This paper examines the comparative impact of these options on two types of putative 'womb‐givers': people who provide gestational surrogacy and those who donate their uterus for live donation. The surrogate 'leases' their womb for the gestational period, while the UTx donor donates their womb permanently via hysterectomy. Both enterprises involve a significant degree of self‐sacrifice and medical risk in order to enable another person(s) to become a parent by either providing gestational labour or enabling the other person to undertake gestation themselves. In this paper, we explore the burdens and the benefits from the perspective of the womb‐giver in order to inform ethical debate about assisted gestation. This is a perspective that is often neglected in the bioethical discourse. With both surrogacy and UTx, when success follows the womb‐giver's sacrifice, the key benefit is delivered to the intending parent(s), but as this article examines, the womb‐giver may also enjoy some unique (relational) benefits as a result of their sacrifice. Ultimately, the choice of how a womb‐giver lends assistance in gestation will impact on their bodily autonomy; some will prefer to carry a pregnancy and others to donate their uterus. We argue that the perspective of the womb‐giver is crucial and thus far has not been afforded sufficient consideration in ethical discussion. [ABSTRACT FROM AUTHOR]

Internationally, there is considerable inconsistency in the recognition and regulation of children's genetic connections outside the family. In the context of gamete and embryo donation, challenges for regulation seem endless. In this paper, I review some of the paths that have been taken to manage children' being closely genetically related to people outside their families. I do so against the background of recognising the importance of children's interests as moral status holders. I look at recent qualitative research involving donor‐conceived people and borrow their own words to make sense of a purported interest to know (of) their close genetic ties. I also review ways in which gamete donation may have facilitated new kinds of kinship, which are at the same time genetic and chosen. In short, in this paper, I explore what meaning there could be in genetic connections that is not about parenthood. Further, I argue that the focus on parenthood in previous work in this area may be detrimental to appreciating some of the goods that can be derived from close genetic connections. [ABSTRACT FROM AUTHOR]

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]

Novel forms of assisted gestation—uterus transplantation and artificial placentas—are highly anticipated in the ethico‐legal literature for their capacity to enhance reproductive autonomy. There are also, however, significant challenges anticipated in the development of novel forms of assisted gestation. While there is a normative exploration of these challenges in the literature, there has not yet, to my knowledge, been empirical research undertaken to explore what reproductive rights organisations and advocates identify as potential benefits and challenges. This perspective is invaluable. These organisations/individuals have an awareness not only of the needs of individuals but also of the political landscape in which regulatory decisions are made and which individuals navigate when seeking reproductive assistance. In this study, data was generated from two semi‐structured focus groups (n = 11). Reflective thematic analysis was used to examine the views raised by study participants in these focus groups. This paper explores two of the themes constructed in the data. First, the equality‐enhancing potential of assisted gestation exploring the multifaceted ways in which assisted gestation has structural benefits for marginalised groups. Second, realising the equality‐enhancing potential of assisted gestation explores the intersecting barriers to access to reproductive technologies and how they may impede the benefits of these technologies in practice. These results can enhance conceptual understanding of the importance of novel forms of assisted gestation and ensure that attention is paid to practical barriers in further normative research. [ABSTRACT FROM AUTHOR]

In this paper, I claim that live uterus donors ought to be considered for the possibility of compensation. I support my claim on the basis of comparable arguments which have already been applied to gamete donation, surrogacy, and other kinds of organ donation. However, I acknowledge that there are specificities associated with uterus donation, which make the issue of incentive and reward a harder ethical case relative to gamete donation, surrogacy, and other kinds of organ donation. Ultimately, I contend that while reimbursement for the costs incurred by live uterus donors should be treated as a necessary ethical minimum, how much further we ought to remunerate uterus donations remains an open question. [ABSTRACT FROM AUTHOR]

Infertility is becoming a public health issue in almost all countries. Assisted Reproductive Technology (ART) is considered as a method of last resort for treating infertility. The treatment of ART is highly expensive and painful, and also the probability of success is low since the success is affected by a large number of variables. Researchers are now trying to identify patterns comprising significant variables, their impact on success, and the interdependence of different variables to enumerate the status of the patient and to support the doctors and biologists to prescribe treatment to improve the probability of success of ART. Machine learning technique is a tool that is used by various researchers in the field of ART to identify the interlink between the variables. The objective of this review paper is to find the appliance of machine learning techniques in ART and to find further enrichment needed for future research. From the literature, it is found that some research works were done using machine learning techniques to predict ART outcome. On analyzing the reviews qualitatively and quantitatively, it is understood that various classifiers are used for ART outcome prediction but they are trained using limited amount of static data collected from fertility centers. The exact prediction of ART outcome may be improved by training the classifier with large amount of dynamic data. But building such a classifier is difficult by the already existing techniques. This may be made possible by introducing Big Data Analytics in ART. [ABSTRACT FROM AUTHOR]

This pclper tells a stoyy of shifting normativities, fom tradition to modernity and back, regarding the recognition of legal parenthood in non-traditional families created through crossborder surrogacy. Tbe cross-border nature of the surrogacy is often forced. as most domestic legalfameworks in Europe still restrict the creation of non-traditional families through assisted reproductive technologies. Once back borne, these families struggle to bave birth certificates recognized and establish legal parenthood. Tbe disjuncture between social reality and domestic law creates a situation of legal limbo. In its recent case law. tbe European Court of Human Rights has pusbed for domestic authorities to rect this situation but, at tbe same time, bas filled the legal limbo witb genetic essentialism and allowed for gender discrimination wben recognizing legal parenthood. While giving full effect to a genetic father's foreign birth certificate based on identity and best interests arguments, tbe Court accepts tbat a genetic mother must adopt to establish a legal parent-child relationship. Tbe paper critically addresses this intriguing imbalance. It deconstructs tbe Court's genetic essentialism encouraging a biologically determined view of parenting, which sidelines tbe social (i.e., non-genetically related) parent and contradicts tbe purpose of assisted reproduction to overcome biological barriers. Tbe paper concludes by rejecting tbe gender-discriminatory element of power and control over legal motberbood imposed by tbe procedural step of adoption. [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]

Evidence suggests that one reason doctors provide certain interventions in assisted reproductive technologies (ART) is because of patient demand. This is particularly the case when it comes to unproven interventions such as 'add‐ons' to in vitro fertilisation (IVF) cycles, or providing IVF cycles that are highly unlikely to succeed. Doctors tend to accede to demands for such interventions because patients are willing to do and pay 'whatever it takes' to have a baby. However, there is uncertainty as to what moral weight should be placed on patient‐led demands in ART, including whether it is acceptable for such demands to be invoked as a justification for intervention. We address this issue in this paper. We start by elucidating what we mean by 'patient‐led demand' and synthesise some of the evidence for this phenomenon. We then argue that a doctor's professional role morality (PRM) yields special responsibilities, particularly in commercialised healthcare settings such as ART, because of the nature of professions as social institutions that are distinct from markets. We argue on this basis that, while there may be reasons (consistent with PRM) for doctors to accede to patient demand, this is not always the case. There is often a gap in justification between acceding to patient‐led demands and providing contested interventions, particularly in commercial settings. As a result, acceding to demand in such settings needs a strong justification to be consistent with PRM. [ABSTRACT FROM AUTHOR]

Recent achievements in reproductive biomedicine have led to a revolution in infertility treatment. A comprehensive understanding of the current status of reproductive medicine is necessary for the development of a forward-looking plan by health policymakers, based on fundamental requirements. This study is a systematic review of the Scopus database to assess reproductive biomedicine publications within Iran and compared to the rest of the world from 1990 to 2020. The data were categorized by geographical distribution across five continents. National data were assessed in comparison with the world and with neighboring countries. Finally, prominent national research institutes in the field of reproductive biomedicine in Iran were identified, and their contributions to the field highlighted. Of the five continents, the highest number of publications and citations is from Europe (36% publications and 41.5% citations). Corresponding numbers for the other continents are 32 and 33% for America, and 26 and 18.4% for Asia respectively. The remaining publications and citations were from Australia (3.8 and 4.1%) and Africa (2.6 and 3.1%). In a national analysis, the highest-ranking institutes in reproductive biomedicine are in Tehran province (50.9% of all Iranian publications), Shiraz (8.8%), Yazd (7.8%), Isfahan (7.1%), and Tabriz (6.9%). More specifically, Tehran University of Medical Science (15.9%), the Royan Institute (12.2%), Shahid Beheshti Medical University (10.1%), Shahid Sadoughi University of Medical Sciences (6.9%), and Tarbiat Modares University (6.7%) account for more than 50% of all Iranian scientific publications. In recent decades, reproductive biomedical research has grown significantly in Iran. Reviewing publications in this field helps health policy decision makers to monitor the direction of research and adjust investment in the treatment of infertility. In addition, it is necessary to expand and organize inter-organizational and international collaborations to improve the research, gain the benefits of different experiences, and engage in international multicenter studies. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a lifelong reproductive endocrine disease, which is the most common cause of anovular infertility. Modern medicine mainly treats infertile patients with PCOS by improving living habits, ovulation induction therapy, and assisted reproductive technology (ART), but the effect is not satisfied. Complementary alternative medicine (CAM) has conspicuous advantages in the treatment of PCOS infertility due to its good clinical efficacy, wide mechanism of action, and no obvious adverse reactions, but its safety and effectiveness in the treatment of PCOS infertility have not been proved. Based on the existing clinical and experimental studies, this paper looks for the therapeutic effect and the mechanism behind it, and explores the safety and effectiveness of its treatment in PCOS infertility, in order to provide reference for future clinical treatment and experimental research. [ABSTRACT FROM AUTHOR]

The treatment of unexplained infertility is a contentious topic that continues to attract a great deal of interest amongst clinicians, patients and policy makers. The inability to identify an underlying pathology makes it difficult to devise effective treatments for this condition. Couples with unexplained infertility can conceive on their own and any proposed intervention needs to offer a better chance of having a baby. Over the years, several prognostic and prediction models based on routinely collected clinical data have been developed, but these are not widely used by clinicians and patients. In this opinion paper, we propose a prognosis-based approach such that a decision to access treatment is based on the estimated chances of natural and treatment-related conception, which, in the same couple, can change over time. This approach avoids treating all couples as a homogeneous group and minimizes unnecessary treatment whilst ensuring access to those who need it early. [ABSTRACT FROM AUTHOR]

Worldwide, over 8 million children and adults are conceived following assisted reproductive technologies (ART), and their long-term health is of consequential public health interest. The objective of this paper is to describe the Growing up Healthy Study (GUHS) cohort in detail, publicise it and invite collaboration. Combining the data collected in the GUHS with other cohorts or databases will improve the much-needed knowledge about the effects of ART, and allow for better understanding of the long-term health outcomes of offspring conceived after ART. The GUHS cohort is a prospective observational study of adolescents and young adults conceived after assisted reproductive technologies (ART). It was established to determine if the long-term health of offspring conceived by ART differs from that of the general population. This was investigated by comparing a substantial number of health parameters to those of a representative population of offspring conceived without ART. The n = 303 GUHS participants were born between 1991–2001 in the two fertility clinics operating at the time in Perth, Western Australia, and undertook assessments at ages 14, 17 and 20, replicating the pre-defined study protocols from the reference cohort—the Raine Study. Participants were comprehensively phenotyped through detailed questionnaires, anthropometry, biochemical analyses, as well as age-specific assessments (asthma, atopy, cardiometabolic health, body composition, mental health, thyroid function, epigenetics and vision). To date the GUHS cohort has been used to study the methylation, cardiometabolic, and thyroid profiles, as well as respiratory and mental health. To summarise, the GUHS cohort provides a valuable addition to the limited knowledge of the long-term health outcomes of ART-conceived offspring. [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 2022, the global commercial surrogacy industry was valued at approximately US$14 billion. This paper explores the issue of surrogacy to reveal how international human rights standards and labor laws treat reproduction as work, building on previous scholarship analyzing similar framing at the grassroots level in Mexico. I argue that the failure to recognize surrogacy as labor is rooted in three lacunae: (1) contemporary policies and practices around surrogacy globally pay little attention to the well-being and rights fulfillment of surrogates themselves, particularly the economic rights of surrogates; (2) the stigma of surrogacy as sexualized care work results in neglect of the labor rights of surrogates in mainstream economic rights discourses; and (3) relevant international rights law has not yet addressed the economic rights of surrogates, nor has it effectively articulated the interdependent relationship between economic rights and reproductive rights. Lastly, I discuss where reproductive rights and economic rights overlap in existing human rights conventions and standards and what possibilities these offer for articulating the interdependence of reproductive and economic rights and for advancing the labor rights of surrogates. [ABSTRACT FROM AUTHOR]

Introduction: People living with human immune virus (HIV) are confronting multiple psychosocial and economic issues influenced by the illness. People on anti-retro viral drugs (ART) were at risk for discontinuation of medications during corona viral disease-2019 (COVID-19) pandemic. COVID-19 outbreak made people living with HIV (PLWH) to experience critical challenges and barriers to optimal care. The experience of people living with HIV such as stigma and discrimination, economic problem, psychosocial problem before the emergency of COVID-19 were studied but there is lack of understanding on the lived experience of people living with HIV in the context of COVID-19 in Ethiopia particularly in Tach Gayint. This study aimed to explore the lived experience of people on ART in context of COVID-19 in Tach Gayint district. Methods and materials: Phenomenological study design conducted with 16 study participants from March 12-April 12/2021. Data were collected using in-depth interview using interview guide and digital recorder. The investigator took note in addition to digital record. Interviews were transcribed word for word and translated conceptually. Analysis followed Reading of transcriptions, develop and apply coding, displaying data, data reduction and interpretation. Atlas.ti-7 software used to facilitate analysis. The quality of data was assured by the principles of credibility, dependability, conformability and transferability. Result: The study explored psychological experience, change in social interaction, and economic experience and ART drug interruption as the main themes including other sub-themes. Most participants perceived the severity of COVID-19 on them. Lack of participation in social activities due to fear of contracting and the participants experienced dying and loss of income. This extreme fear pushed some participants to interrupt their daily ART intake especially during lock down period. Personal, familial and community context contributed for these distressing experiences. Conclusion and recommendation: This study reported participants' psychosocial, economic experiences including ART drug interruptions. The government should design policies and interventions to alleviate their personal, household and community problems, which were the caused for the mentioned hostile experiences. [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]

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Objective. The aim of this paper was to investigate whether two freeze-thaw cycles before embryo transfer may affect perinatal and neonatal outcomes. Materials and Methods. A total of 8,028 frozen-thawed embryo transfer patients who became pregnant between March 2013 and September 2019 were included. The patients were divided into two groups: the oocyte cryopreservation (OC) group (N = 96) and the control group (N = 7932). Propensity score matching (PSM) was used to adjust the baseline characteristics of the two groups at a proportion of 1 : 4. There were 96 patients in the OC group and 369 patients in the control group after PSM. The pregnancy-related complications and neonatal conditions after delivery of the two groups were compared. Results. The OC group had a higher stillbirth rate (3.1% vs. 0.3%, P = 0.029) than the control group after PSM. Moreover, a slightly higher pregnancy defect rate was found in the OC group. There was no significant difference in the rates of diabetes mellitus, hypertension during pregnancy, cesarean section, multiple births, low birth weight (LBW), or premature birth defects between the two groups. Conclusions. Our findings demonstrate that performing frozen-thawed embryo transfer (FET) with cryopreserved oocytes was associated with a higher rate of stillbirth than FET with fresh oocytes. The incidences of diabetes, gestational hypertension, cesarean section, multiple births, LBW, premature birth, and birth defects of the two groups were not significantly different. [ABSTRACT FROM AUTHOR]

Introduction-Background: Medical tourism constitutes a rising sector of the tourism industry, as several countries around the world are welcoming thousands of tourists daily who visit them in order to receive medical services, usually combining them with short-term holidays. Infertility and other diseases affecting conception cause a large number of couples to resort to the resolution of assisted reproduction. Assisted Reproductive Technologies (ART) is an important means of tackling infertility and other conditions that prevent young couples from conceiving. The aim of this paper is to investigate the development of medical tourism related to assisted reproduction technology (ART) methods worldwide and its growth perspectives (future prospects and trends for sustainable development and investments) in Cyprus. Methods: A systematic literature review was conducted on September - October 2017. The search was conducted in the PubMed and Google Scholar databases using as keywords medical tourism, assisted reproductive technology, medical tourism and assisted reproductive technology in Cyprus, etc. The inclusion criteria were articles/studies published from 2009-2017, Cyprus as the country of medical tourism destination, studies published in English and Greek and in acknowledged scientific journals and inclusion of certain types of studies (reviews, surveys, observational studies, case studies, cross-sectional studies and qualitative studies). Results: Initially 508 papers from the above-mentioned databases were identified. Of the 508, 90 were rejected after reading the title (duplicate entries or they had no summary or were not written in the language of choice), 178 were rejected after reading the summary (they were conducted before 2009) and 172 were rejected because they did not refer to the assisted reproductive tourism as a branch of the medical tourism. Of the remaining 68, 46 were rejected after studying the entire text as they did not again address the subject under study. The studies included in the review unraveled several factors that define the development of medical tourism related to assisted reproduction technology (ART) methods worldwide (e.g. demographic changes i.e. the aging population, the high cost of treatment in the high-income origin countries and the respective long waiting lists, the changes in the family structure and other economic, social, political, religious and legal constraints, etc) and highlighted the prominent growth opportunities for the Cypriot context. Conclusions: Medical tourism related to assisted reproduction technology (ART) methods is dynamically growing and countries like Cyprus has the potential to succeed in expanding its economy by investing in medical equipment, investments in healthcare facilities and the synergy between public and private ventures. [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]

An editorial is presented Ectogenesis may be partial or full. Full ectogenesis refers to a complete alternative to human gestation. Topics include this special issue of ectogenesis comprises eight papers from scholars working in bioethics, philosophy, law and neonatology; and the issue opens with Zeljka Buturovic's provocative article, in which she compares two dichotomies.

Study Question: How many twins are born in human populations and how has this changed over recent decades?Summary Answer: Since the 1980s, the global twinning rate has increased by a third, from 9.1 to 12.0 twin deliveries per 1000 deliveries, to about 1.6 million twin pairs each year.What Is Known Already: It was already known that in the 1980s natural twinning rates were low in (East) Asia and South America, at an intermediate level in Europe and North America, and high in many African countries. It was also known that in recent decades, twinning rates have been increasing in the wealthier parts of our world as a result of the rise in medically assisted reproduction (MAR) and delayed childbearing.Study Design, Size, Duration: We have brought together all information on national twinning rates available from statistical offices, demographic research institutes, individual survey data and the medical literature for the 1980-1985 and the 2010-2015 periods.Participants/materials, Setting, Methods: For 165 countries, covering over 99% of the global population, we were able to collect or estimate twinning rates for the 2010-2015 period. For 112 countries, we were also able to obtain twinning rates for 1980-1985.Main Results and the Role Of Chance: Substantial increases in twinning rates were observed in many countries in Europe, North America and Asia. For 74 out of 112 countries the increase was more than 10%. Africa is still the continent with highest twinning rates, but Europe, North America and Oceania are catching up rapidly. Asia and Africa are currently home to 80% of all twin deliveries in the world.Limitations, Reasons For Caution: For some countries, data were derived from reports and papers based on hospital registrations which are less representative for the country as a whole than data based on public administrations and national surveys.Wider Implications Of the Findings: The absolute and relative number of twins for the world as a whole is peaking at an unprecedented level. An important reason for this is the tremendous increase in medically assisted reproduction in recent decades. This is highly relevant, as twin deliveries are associated with higher infant and child mortality rates and increased complications for mother and child during pregnancy and during and after delivery.Study Funding/competing Interest(s): The contribution of CM was partially supported by the European Research Council (ERC) under the European Union's Horizon 2020 Research and Innovation Programme (grant No 681546, FAMSIZEMATTERS), Nuffield College, and the Leverhulme Trust. The contribution of GP was partially supported by the French Agence Nationale de la Recherche (grant No ANR-18-CE36-0007-07). The authors declare no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Assisted reproductive technologies have greatly increased our control over reproductive choices, leading some bioethicists to argue that we face unprecedented moral obligations towards progeny. Several models attempting to balance the principle of procreative autonomy with these obligations have been proposed. The least demanding is the minimal threshold model (MTM), according to which every reproductive choice is permissible, except creating children whose lives will not be worth living. Hence, as long as the future child is likely to have a life worth living, prospective parents may be allowed to use preimplantation genetic diagnosis (PGD) to select embryos with genetic diseases or disabilities. Assuming a consequentialist person‐affecting view of morality, this paper investigates whether the MTM is an appropriate tool to guide procreative decisions given the continuous development of reproductive genetic technologies. In particular, I consider germline genome editing (GGE) and I argue that its application in human reproduction, unlike PGD, should be conceived as person‐affecting towards future progeny. I claim that even if we assume the plausibility of the MTM within PGD, we are committed to accepting that a greater moral obligation towards progeny should guide procreative decisions if GGE were available. In this case, the MTM should no longer be considered an appropriate instrument to guide procreative choices. Finally, I investigate when we face this greater moral obligation, concluding that it applies only when prospective parents have already engaged in the in vitro fertilization process. [ABSTRACT FROM AUTHOR]

Study Question: Is bacterial vaginosis (BV) associated with fecundability?Summary Answer: Women with BV may be at increased risk for sub-fecundity.What Is Known Already: While BV has been associated with poor IVF outcomes, the association between vaginal microbiota disruption and non-medically assisted conception has not been thoroughly explored.Study Design, Size, Duration: Kenyan women with fertility intent were enrolled in prospective cohort that included monthly preconception visits with vaginal fluid specimen collection and pregnancy testing. Four hundred fifty-eight women attempting pregnancy for ≤3 menstrual cycles at enrollment were eligible for this fecundability analysis.Participants/materials, Setting, Methods: At monthly preconception visits, participants reported the first day of last menstrual period and sexual behavior, underwent pregnancy testing and provided vaginal specimens. Discrete time proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% CI in menstrual cycles with and without BV (Nugent score ≥ 7) at the visit prior to each pregnancy test. We also assessed the association between persistent BV (BV at two consecutive visits) and fecundability.Main Results and the Role Of Chance: Participants contributed 1376 menstrual cycles; 18.5% (n = 255) resulted in pregnancy. After adjusting for age, frequency of condomless sex and study site, BV at the visit prior to pregnancy testing was associated with a 17% lower fecundability (adjusted FR (aFR) 0.83, 95% CI 0.6-1.1). Persistent BV was associated with a 43% reduction in fecundability compared to cycles characterized by optimal vaginal health (aFR 0.57, 95% CI 0.4-0.8).Limitations, Reasons For Caution: Detection of vaginal microbiota disruption using Gram stain and a point-of-care test for elevated sialidase identified a non-optimal vaginal environment, but these non-specific methods may miss important relationships that could be identified by characterizing individual vaginal bacteria and bacterial communities using molecular methods. In addition, results may be subject to residual confounding by condomless sex as this was reported for the prior month rather than for the fertile window during each cycle.Wider Implications Of the Findings: Given the high global prevalence of BV and infertility, an association between BV and reduced fecundability could have important implications for a large number of women who wish to conceive. Multi-omics approaches to studying the vaginal microbiota may provide key insights into this association and identify potential targets for intervention.Study Funding/competing Interest(s): This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-R.S.M.). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were made possible using REDCap electronic data capture tools hosted at the University of Washington's Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for consulting from Lupin Pharmaceuticals. L.E.M. receives research funding, paid to the University of Washington, from Hologic Corporation, and has received honoraria for service on scientific advisory boards from Hologic and Nabriva Therapeutics.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background: Human cloning is a recent occurrence that is not confined to bio-issues; rather, it has provoked numerous questions worldwide and presented scientific and religious challenges. These series of articles aim to examine the proposed approaches and analyze the aspects of human cloning in terms of tenets, morals, jurisprudence, and laws. In this paper, we analyze the ideological and theological evidences, regardless of scientific, ethical and legal problems that exist in the reproduction method. Materials and Methods: We used a descriptive-analytical method to consider the challenges of human cloning according to the "system of Divine creativity" and "the will of God", as well as the "pairing system" and "diversity in nature" with emphasis on the Holy Qur'an and Qur'anic commentaries. Results: According to the Qur'an, although any type of physical changes and retouching of the human body are forbidden, the alteration of God's creation may not prove the prohibition of cloning. Cloning is not contradictory to the principle, precedent, and rule of coupling, and it may be one of the hidden precedents of creation. Therefore, not only does a clone not contradict the precedent of the variety of men, but this variety is a sign for men and not a precedent predominated over the order of nature. Conclusion: It is proven that cloning does not give life; instead, it utilizes the life bestowed by God. This technique does not contradict the precedents of existence. It is a way to discover some precedents of God and is under the order of cause and effect of the world. Cloning is not considered as a challenge to human beliefs, nor is it a change in Divine creation. Moreover, cloning does not contradict the theological teachings and concepts of the Holy Qur'an and Shiite Muslims. [ABSTRACT FROM AUTHOR]

Over the years, the demand for ART with donated embryos has increased. Treatment can be performed using donated 'surplus embryos' from IVF treatment or with embryos intentionally created through so-called 'double gamete donation'. Embryo donation is particularly sensitive because treatment results in the absence of a genetic link between the parent(s) and the child, creating complex family structures, including full genetic siblings living in another family in the case of surplus embryo donation. In this paper, we explore the ethical acceptability of embryo donation in light of the similarities and differences between surplus embryo donation and double gamete donation. We will argue that no overriding objections to either form of embryo donation exist. First of all, ART with donated embryos respects patients' reproductive autonomy by allowing them to experience gestational parenthood. It also respects IVF patients' reproductive autonomy by providing an additional option to discarding or donating surplus embryos to research. Second, an extensive body of empirical research has shown that a genetic link between parent and child is not a condition for a loving caring relationship between parent(s) and child. Third, the low moral status of a pre-implantation embryo signifies no moral duty for clinics to first use available surplus embryos or to prevent the development of (more) surplus embryos through double gamete donation. Fourth, there is no reason to assume that knowledge of having (full or half) genetically related persons living elsewhere provides an unacceptable impact on the welfare of donor-conceived offspring, existing children of the donors, and their respective families. Thus, patients and clinicians should discuss which form of ART would be suitable in their specific situation. To guarantee ethically sound ART with donated embryos certain conditions have to be met. Counselling of IVF patients should involve a discussion on the destination of potential surplus embryos. When counselling donors and recipient(s) a discussion of the significance of early disclosure of the child's mode of conception, the implications of having children raised in families with whom they share no genetic ties, expectations around information-exchange and contact between donor and recipient families or genetically related siblings is warranted. Importantly, conclusions are mainly drawn from results of empirical studies on single gamete donation families. To evaluate the welfare of families created through surplus embryo donation or double gamete donation additional empirical research on these particular families is warranted. [ABSTRACT FROM AUTHOR]

The goal of this paper is both modest and ambitious. The modest goal is to show that intercountry adoption should be considered by ethicists and healthcare providers. The more ambitious goal is to introduce the many ethical issues that intercountry adoption raises. Intercountry adoption is an alternative to medical, assisted reproduction option such as in vitro fertilization (IVF), intracytoplasmic sperm injection, third party egg and sperm donation and surrogacy. Health care providers working with assisted reproduction are in a unique position to introduce their clients to intercountry adoption; however, providers should only do so if intercountry adoption is ethically equal or superior to the alternatives. This paper first presents a brief history of intercountry adoption. The second section compares intercountry adoption with medical alternatives. The third section examines the unique ethical challenges that are not shared by other medical alternatives. The final section concludes that it is simplistic for a healthcare provider to promote intercountry adoption unconditionally; however, in situation where intercountry adoption is practiced conscientiously it poses no greater ethical concern than several medical alternatives. This conclusion is preliminary and is intended as a start for further discussion. [ABSTRACT FROM AUTHOR]

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Background: Many studies have demonstrated the benefits of the addition of growth hormone (GH) to the controlled ovarian stimulation protocol in vitro fertilization (IVF) cycles in poor-respond patients, but the effect of GH on patients with poor embryonic development remain unclear. This paper was designed to investigate the efficacy of GH co-treatment during IVF for the patients with poor embryonic development.Method: A randomized controlled trial including 158 patients with poor embryo development was conducted between July 2017 and February 2019. One hundred and seven patients were randomized for GH treatment (GH group) and 51 patients for untreated (control group). The primary end-points were the clinical pregnancy and live birth rates in the two groups. The oocyte competence were assessed through calculating the mitochondrial DNA (mtDNA) copy number in corresponding cumulus granulosa cells (CGCs). Quantitative PCR were used for calculation of mtDNA copy number.Results: Relative to the control group, GH co-treatment resulted in a significantly higher number of retrieved oocytes (10.29 ± 5.92 versus 8.16 ± 4.17, P = 0.023) and cleaved embryos (6.73 ± 4.25 versus 5.29 ± 3.23, P = 0.036). The implantation rate, clinical pregnancy rates per cycle, and live birth rate per cycle were higher in the GH group than in the control group (36.00% versus 17.86%, P = 0.005; 43.93% versus 19.61%, P = 0.005; 41.12% versus 17.65%, P = 0.006). CGCs of the GH group had significantly higher mtDNA copy numbers than CGCs of the control group (252 versus 204, P < 0.001).Conclusions: These data provided further evidence to indicate that GH supplementation may support more live births during IVF, in patients with poor embryonic development. It also appears that oocytes generated under GH co-treatment have a better developmental competence.Trial Registration: ChiCTR1900021992 posted March 19, 2019 (retrospectively registered). [ABSTRACT FROM AUTHOR]

Full ectogenesis as the complete externalization of human reproduction by bypassing the bodily processes of gestation and childbirth can be considered the culmination of genetic and reproductive technologies. Despite its still being a hypothetical scenario, it has been discussed for decades as the ultimate means to liberate women from their reproductive tasks in society and hence finally end fundamental gender injustices generally. In the debate about the application of artificial wombs to achieve gender equality, one aspect is barely mentioned but is of crucial relevance from a medical‐ethical perspective: whether and how could full ectogenesis be justified as a proper use of medicine? After characterizing the technology as a special form of human enhancement and as an extension of medical practice that goes beyond the traditional field of medicine, this paper critically assesses the theoretical possibilities of legitimizing this extension. We identify two ways of justification: either one argues that ectogenesis fulfils a proper goal of medicine (a justification we call pathologization), or one argues that the application of ectogenesis achieves a non‐medical goal (which we call medicalization). Because it is important from a medical‐ethical point of view to avoid an inappropriate instrumentalization or misuse of medicine and thus an undue medicalization of non‐medical problems, a set of necessary conditions has to be met. It is doubtful whether full ectogenesis for non‐medical purposes could fulfil these conditions. Rather, its comprehensive usage could be seen as a revolutionary modification of what it means to be human. [ABSTRACT FROM AUTHOR]

Potential applications of genome editing in assisted reproductive technology (ART) raise a vast array of strong opinions, emotional reactions and divergent perceptions. Acknowledging the need for caution and respecting such reactions, we observe that at least some are based on either a misunderstanding of the science or misconceptions about the content and flexibility of the existing legal frameworks. Combining medical, legal and ethical expertise, we present and discuss regulatory responses at the national, European and international levels. The discussion has an EU starting point and is meant as a contribution to the general international regulatory debate. Overall, this paper concludes that gene editing technologies should not be regulated autonomously. Rather, potential uses should be regulated under general, existing frameworks and where applicable by reference to sufficiently equivalent technologies and techniques already subject to specific regulation. To be clear, we do not argue for the hasty introduction of gene editing as a reproductive treatment option in the immediate future. We call for caution with regard to overreaching moratoria and prohibitions that will also affect basic research. We recommend flexible regulations that allow for further responsible research into the potential development of the technology. We call for an open and inclusive debate and argue that scientific communication should claim a more prominent role to counter the danger of widespread misinformation. A high level of transparency and accuracy should guide scientific communication while simultaneously global‐scale responsibility and governance should be fostered by promoting cross‐disciplinary thinking and multi‐level stakeholder involvement in legal and regulatory processes. [ABSTRACT FROM AUTHOR]

In vitro gametogenesis (IVG) might offer numerous research and clinical benefits. Some potential clinical applications of IVG, such as allowing opposite‐sex couples experiencing infertility to have genetically related children, have attracted support. Others, such as enabling same‐sex reproduction and solo reproduction, have attracted significantly more criticism. In this paper, we examine how different ethical principles might help us to draw lines and distinguish between ethically desirable and undesirable uses of IVG. We discuss the alleged distinction between therapeutic and non‐therapeutic uses of assisted reproduction in the context of IVG, and show how it is both problematic to apply in practice and theoretically dubious. We then discuss how the ethical principles of reproductive justice and beneficence apply to IVG for opposite‐sex reproduction, same‐sex reproduction, and solo reproduction. We suggest that these principles generate strong reasons for the use of IVG for opposite‐sex and same‐sex reproduction, but not for solo reproduction. [ABSTRACT FROM AUTHOR]

Though greatly routinized over the past two decades, assisted reproductive technologies still invoke an occasional public debate around a dilemma that is constituted as unprecedented. This paper examines one such case that took place in Israel—that of a legal dispute between estranged partners over the right to have their fertilized eggs implanted in a surrogate mother's womb. The paper probes the political repercussions of the case in terms of the impact on the pronatalist local order and gender relations. It shows that certain subjects, mostly those of a more ‘female’ domestic character, received exceptional public attention and indeed called into question prevailing ideas and power relations. At the same time, in other contexts of the debate, the status quo was reaffi rmed within an updated framework. On the whole, the dilemma at hand and the innovative options enabled by technology were largely contained within the established gender order. Still, the case did contribute, if modestly, to women's rights and autonomy. The paper's conclusion suggests that public debates regarding reproductive disruptions may become a vehicle for both patriarchal gender relations and social transformation. [ABSTRACT FROM AUTHOR]

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Discussions of nonhuman research ethics tend to focus on what we owe nonhuman research subjects in laboratory settings only. But humans make critical decisions about these animals outside the lab, too, during breeding, transportation, and end-of-study protocols. This article reviews extra-lab risks and harms to nonhuman research subjects, focusing on the most commonly and intensively used animals like rodents and fishes, and argues that extra-lab risks and harms merit ethical consideration by researchers and institutional review. [ABSTRACT FROM AUTHOR]

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