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In the Federal Republic of Germany, intentional alteration of the genome of germline cells and embryos is prohibited by criminal law. This ban is the result of legislation that was adopted more than twenty-five years ago. However, the rapid emergence of genome manipulation techniques, coupled with recent technological developments, is increasingly exposing the senescence of the regulatory framework. With the advent of genome editing, there has been a shift in the national debate on the use of genetic engineering. Until recently, the discussion regarding the use of genome altering methods had been more about the application of genetic engineering to plants (so-called ‘green genetic engineering’) than to humans (so-called ‘red genetic engineering’). After all, green genetic engineering has been present in the fields for years, and sometimes even on the plate, while most red genetic engineering efforts have been unspectacular cell biology basic research, slowed down by both technical and legal hurdles. However, the emergence of more precise, safer and more predictable genome editing methods has now brought the issue into German public discourse and, as evidenced by this volume, around the world.
The aim of this chapter is to provide an overview of the constitutional and legal landscape in Mexico regarding healthcare and health research systems, in order to establish the potential implications for human genome engineering. In doing so, it first explores the recent constitutional changes in relation to the protection of human rights in the country and Latin America. It establishes that a progressive interpretation of the Mexican constitution in line with the international treaties on human rights signed and ratified by Mexico could be the way forward in permitting basic and applied health research, specifically via using CRISPR/Cas to modify the human germline genome for the benefit of human health. Due to the fact that the existing legal provisions in place are so fragmented and there is a lacuna regarding specific regulation of the human genome, it is feasible to propose that by applying a human rights purposive approach in favour of the right to freedom of science and right to be benefited from scientific progress, research on human germline genome editing should be legally possible. This is also supported by the case jurisprudence that has been developed by the Latin American Court of Human Rights regarding access to assisted reproduction technologies.
This paper investigates the contemporary phenomenon of smuggling sperm from within Israeli jails, which I treat as a biopolitical act of resistance. Palestinian prisoners who have been sentenced to life-imprisonment have recently resorted to delivering their sperm to their distant wives in the West Bank and Gaza where it is then used for artificial insemination. On the level of theory, my analysis of this practice benefits from Jacques Derrida's commentary in The Post Card on imaginative postal delivery of sperm to distant lovers. I use Derrida's heteronormative implication to examine how Palestinian prisoners defy the Israeli carceral system via the revolutionary act of sperm smuggling. The article then argues that smuggling sperm challenges the conventional gender codes in Palestinian society that see women in passive roles. Drawing on Derrida's metaphorical connection between masturbation and writing, I problematize the perception of speech/orality as primary in traditional Palestinian culture. Women, who mostly act as smugglers, become social agents whose written stories of bionational resistance emerge as a dominant mode of representation.
The aim of this study was to investigate if there is an adverse effect of multiple controlled ovarian stimulation (COS) on the maturity of oocytes (MI and MII), fertilization rate, embryo developmental qualities and clinical pregnancy rates in donation cycles. In total, 65 patients undergoing oocyte donation cycles multiple times were included in this study. Patients were grouped as group A that consisted of donors with ≤2 stimulation cycles while B consisted of donors with ≥3 stimulation cycles; and group C included donors who had ≤15 oocytes, while group D had donors with ≥16 oocytes. Numbers of oocytes obtained, MI and MII oocytes, fertilization, embryo quality and clinical pregnancy outcomes were compared. Significant statistical differences were observed in total number of oocytes obtained, maturity of oocytes (MI and MII), fertilization rate, embryo qualities and clinical pregnancy outcomes of donors in groups A–D. Donors with ≤2 ovarian stimulation cycles had lower numbers of immature oocytes than donors with three or more stimulation cycles. However, donors with ≥3 stimulation cycles had higher numbers of mature oocytes, zygotes, with better day 3 embryo qualities and higher clinical pregnancy rates than donors with ≤2 stimulation cycles. Repeated COS does not seem to have any adverse effect on ovarian response to higher dose of artificial gonadotropin, as quality of oocytes collected and their embryological developmental potential were not affected by the number of successive stimulation cycles. The effect of multiple COS on the health of the oocyte donor needs to be assessed for future purpose.
Choosing ART treatment is a major life decision. Patients have a fundamental right to patient-centered healthcare that respects their unique needs, preferences and values.
At the heart of a patient’s question about success rates is the need to know whether they can be assured of the best chance of taking home a healthy baby.
However, choosing a clinic based solely on reported success rates can create unrealistic expectations, as pregnancy rates vary tremendously, depending on the type of treatment, the age and cause of infertility. ‘League Tables’ comparing the performance of one clinic to another can be misleading.
More than 25 years’ experience from patients’ organizations suggest that many pursue ART without fully understanding the risks and potential complications. The format of ART surveillance reports varies considerably and are usually written for a scientific audience.
Therefore, ART surveillance data should be available in a format that is unbiased, understandable and meaningful.
ART was pioneered in Africa in the 1980’s. Subsequently, ART centres emerged around the continent, mostly by specialists acquiring skills abroad. Despite this, ART activity remains scant in most African countries and absent in several others.
Historically, ART surveillance in Africa has been similarly scant and fragmented. Recently however, the African Network and Registry for ART (ANARA) has been established with the vision to reduce the high burden of infertility in Africa through ART; and its mission to bring together ART centres within and across countries and to collect data pertaining to availability, utilization, effectiveness and safety of ART. First registry data, collected from 40 centres in 13 countries, and will be published shortly. ANARA protects the anonymity of centres and patients and the ownership of data.
The successful establishment of ANARA is rooted in a collaborative spirit of engagement with ART centres and other stakeholders, developmental assistance from both the Latin American and World Registry, and the importance of data in reducing the burden of infertility in Africa.
Asia is composed of more than 40 countries where about 60% of the global population live. Since Asia is the largest and geographically variable continent, where cultural and social backgrounds are very diverse in every part of this area, it is almost impossible to describe the whole area in one chapter. Rapid decline of birth rates in multiple countries, particularly in eastern Asia, drew wide public attention and promoted the treatment and care for infertile couples. Particularly, assisted reproductive technology (ART) has significantly spread in many Asian countries and its growth is still ongoing. Although ART registries were established in several Asian countries many years ago, there is no Asian regional registry because of this diverse situation of this area.
The International Committee Monitoring Assisted Reproductive Technologies (ICMART) has reported global ART results, helped create and improve national and regional registries, and promoted standardization of international terminology through development and revision of glossaries. These accomplishments have required the dedication and expertise of many professionals over several decades. ICMART’s history is instructive for those developing or improving their own registries. Creation of a formal structure is essential to success and sustainability of a registry. Development of relationships and formal partnerships hastens progress and benefits all stakeholders. The initial development of the glossary involved the World Health Organization (WHO). The third revision has the participation of essentially all major global stakeholders. Registries have significant value for professionals, patients and policy makers. ICMART’s registry reports utilization, profile of procedures and patients, effectiveness and safety. Despite much progress, many data collection and reporting difficulties remain. However, collaboration in addressing these challenges is resulting in major progress and also bringing many collateral benefits, especially enhanced professional relationships and harmonized approaches to problems. The future will see more comprehensive and higher quality registries, harmonized data collection, the use of “big data” analytics and artificial intelligence to increase the value of registries for patient care, research, public education and policy makers.
Since 1999 surveillance of ART in Europe is carried out by the European IVF-monitoring (EIM) Consortium, founded in June 1999 by the European Society of Human Reproduction and Embryology (ESHRE). EIM is organized by the representatives of national registries of European countries offering ART. The high diversity of participating European countries pose a serious challenge for obtaining complete data and interpreting the results. Notwithstanding this challenge EIM has managed in 2014 to collect the data of 38 from 42 participating European countries (90.5%) and 1280 institutions (90.2% of all known in Europe). Annual meetings supported by ESHRE have created a spirit of mutual understanding and have contributed much to increase the level of participation. Every year, EIM published an annual report with cross-sectional data, typically made of more than 700'000 treatment cycles of ART. The first data set of 1997 was published in 2001 and was followed by 17 reports in the journal „Human Reproduction“.
This special issue adopts a comparative approach to the politics of reproduction in twentieth-century France and Britain. The articles investigate the flow of information, practices and tools across national boundaries and between groups of experts, activists and laypeople. Empirically grounded in medical, news media and feminist sources, as well as ethnographic fieldwork, they reveal the practical similarities that existed between countries with officially different political regimes as well as local differences within the two countries. Taken as a whole, the special issue shows that the border between France and Britain was more porous than is typically apparent from nationally-focused studies: ideas, people and devices travelled in both directions; communication strategies were always able to evade the rule of law; contraceptive practices were surprisingly similar in both countries; and religion loomed large in debates on both sides of the channel.
The birth of Louise Brown, the world’s first ‘test-tube baby’, has come to signify the moment at which technologically assisted human reproduction became a re ality. This was a highly mediated and visible reality, as this article explores through the example of a British television documentary about Louise Brown broadcast when she was just six weeks old, ‘To Mrs Brown… A Daughter’ (Thames Television, 1978). In the article, I discuss the programme alongside data from an interview with its producer, Peter Williams. Williams sought to convince the public that IVF was morally acceptable and to cultivate sympathy for the infertile through this film. I will consider how he went about this by focusing on the programme’s visual presentation of Louise Brown, Peter Williams’ aims in making the film and his sympathetic relationship with the ‘pioneers’ of IVF, gynaecologist Patrick Steptoe and physiologist Robert Edwards. I will conclude with a discussion of the political implications of this film and how it contributed to the normalisation of IVF at a pivotal moment in its history.
HLA-G expression has been detected in early preimplantation embryos and it has been postulated that a relationship between embryonic expression of this factor and successful pregnancy may exist. Forty-six patients were prospectively selected from our centre ‘Unidad de Reproducción Humana, Hospital Universitario de Canarias’ for conducting this study. In all cases, metaphase II (MII) oocytes were fertilized using intracytoplasmic sperm injection 2–4 h after retrieval. Embryos were cultured individually in 20 µl droplets of G-1 medium (VitroLife) under oil at 37°C and a 6% CO2 environment. Fertilization was assessed at 18 h postinsemination and all oocytes fertilized were passed into a new culture plaque individually in 300 µl culture medium until day 3 of culture. The culture medium was examined for the expression and secretion of sHLA-G with a sandwich enzyme-linked immunosorbent assay kit (BioVendor, Heidelberg, Germany) according to the manufacturer’s instructions. We found statistical significance between higher levels of sHLA-G secretion and pregnancy rate. When both groups were compared there was no difference in embryo quality of transferred embryos, but a significant difference in the number of oocytes and the embryo quality of the cohort existed that was greater in the pregnant group. A standardized sHLA-G assay with a specifically defined range and standard units provides a non-invasive method to identify the most competent embryos for transfer.
The aim of the current study was to investigate the effect of caffeine supplementation during in vitro maturation (IVM) for different maturation times on the developmental potential of canine oocytes recovered from ovariohysterectomized bitches. The recovered cumulus–oocytes complexes were in vitro matured for 72 h. Here, 10 mM caffeine was added to the maturation medium for different incubation times (caffeine from 0–72 h maturation, caffeine for the first 24 h of maturation only, caffeine addition from 24 to 48 h maturation time, caffeine addition from 48 to 72 h maturation or in caffeine-free medium, control group). The matured oocytes were in vitro fertilized using frozen–thawed spermatozoa. The presumptive zygotes were in vitro cultured in synthetic oviductal fluid medium for 5 days. The results showed that both maturation and fertilization rates were significantly higher (P ˂ 0.05) using caffeine-treated medium for the first 24 h of maturation compared with the control and other two groups of caffeine treatment (from 24 to 48 h and from 48 to 72 h), whereas use of caffeine-treated medium for a 0–72 h incubation time did not affect these rates (P > 0.05). Interestingly, the matured oocytes in caffeine-supplemented medium for the first 24 h or from 0–72 h showed a significant (P ˂ 0.05) increase in the total number of cleaved embryos compared with the control group. In conclusion, supplementation of the maturation medium with 10 mM caffeine for the first 24 h of maturation or during the whole maturation time (0–72 h) improved nuclear maturation and subsequent embryo development preimplantation following in vitro fertilization.
Most wild equids and many domestic horse breeds are at risk of extinction, so there is an urgent need for genome resource banking. Embryos cryopreservation allows the preservation of genetics from male and female and is the fastest method to restore a breed. In the equine, embryo production in vitro would allow the production of several embryos per cycle. Intracytoplasmic sperm injection (ICSI) is used to generate horse embryos, but it requires expensive equipment and expertise in micromanipulation, and blastocyst development rates remain low. No conventional in vitro fertilization (IVF) technique for equine embryo production is available. The development of culture conditions able to mimic the maturation of the oocyte in preovulatory follicular fluid (pFF) and the post-maturation in oviductal fluid (OF) may improve embryo production in vitro. Our aim was to analyse the effect of in vitro maturation in pFF and incubation in OF on in vitro maturation of equine oocytes, fertilization using conventional IVF or ICSI, and embryo development after culture in synthetic oviductal fluid (SOF) or DMEM-F12. Oocytes collected from slaughtered mares or by ovum pick up were matured in vitro in pFF or semi-synthetic maturation medium (MM). The in vitro maturation, fertilization and development rates were not statistically different between pFF and MM. After in vitro maturation, oocytes were incubated with or without OF. Post-maturation in OF did not significantly improve the fertilization and development rates. Thus, in our study, exposure to physiological fluids for oocyte maturation and post-maturation does not improve in vitro embryo production in the horse.
The use of assisted reproductive technologies (ART) has increased significantly, allowing many coping with infertility to conceive. However, an emerging body of evidence suggests that ART could carry epigenetic risks for those conceived through the use of these technologies. In accordance with the Developmental Origins of Health and Disease hypothesis, ART could increase the risk of developing late-onset diseases through epigenetic mechanisms, as superovulation, fertilization methods and embryo culture could impair the embryo’s epigenetic reprogramming. Such epigenetic risks raise ethical issues for all stakeholders: prospective parents and children, health professionals and society. This paper focuses on ethical issues raised by the consideration of these risks when using ART. We apply two key ethical principles of North American bioethics (respect for autonomy and non-maleficence) and suggest that an ethical tension may emerge from conflicting duties to promote the reproductive autonomy of prospective parents on one hand, and to minimize risks to prospective children on the other. We argue that this tension is inherent to the entire enterprise of ART and thus cannot be addressed by individual clinicians in individual cases. We also consider the implications of the ‘non-identity problem’ in this context. We call for additional research that would allow a more robust evidence base for policy. We also call upon professional societies to provide clinicians with guidelines and educational resources to facilitate the communication of epigenetic risks associated with ART to patients, taking into consideration the challenges of communicating risk information whose validity is still uncertain.
Concerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health. We will also examine the potential factors that may contribute to these health risks, and discuss underlying mechanisms, including epigenetic changes that may occur during the preimplantation period and reprogram development in utero, and adult health, later in life. Lastly, this review will consider the future directions with the view to optimize the long-term health of ART children.
Medically assisted reproductive technologies, such as in vitro embryo production, are increasingly being used to palliate infertility. Eggs are produced following a hormonal regimen that stimulates the ovaries to produce a large number of oocytes. Collected oocytes are then fertilized in vitro and allowed to develop in vitro until they are either frozen or transferred to mothers. There are controversial reports on the adverse impacts of these technologies on early embryos and their potential long-term effects. Using newly developed technological platforms that enable global gene expression and global DNA methylation profiling, we evaluated gene perturbations caused by such artificial procedures. We know that cells in the early embryo produce all cells in the body and are able to respond to their in vitro environment. However, it is not known whether gene perturbations are part of a normal response to the environment or are due to distress and will have long-term impacts. While the mouse is an established genetic model used for quality control of culture media in clinics, the bovine is a large mono-ovulating mammal with similar embryonic kinetics as humans during the studied developmental window. These model systems are critical to understand the effects of assisted reproduction without the confounding impact of infertility and without the limitations imposed by the scarcity of donated human samples and ethical issues. The data presented in this review come mostly from our own experimentation, publications, and collaborations. Together they demonstrate that the in vitro environment has a significant impact on embryos at the transcriptomic level and at the DNA methylation level.
Sperm preparation is an important step in the in vitro production of embryos. Centrifugation through colloids has been used to select normal sperm for assisted reproduction in several species. Animal models can sometimes be used as a preliminary step to investigate sperm preparation methods that are potentially of use for human fertility treatments. In this study bovine semen was prepared using three variants of the single-layer centrifugation sperm selection technique (Small, Mini, Mini-EP) with Bovicoll (Androcoll-B). Computer-assisted sperm motility analysis, the hypo-osmotic swelling test, and the sperm chromatin structure assay were performed on unselected (control) and SLC-selected sperm samples. Mini and Mini-EP gave the highest yield of motile spermatozoa, progressive motility and membrane integrity. In vitro fertilization trials were performed to investigate the fertilizing ability of the frozen–thawed bovine spermatozoa selected with Bovicoll. Mini-SLC (single-layer centrifugation) and swim-up (Control) were performed and cleavage rate and blastocyst rate did not differ significantly between groups. As there was a trend to an increased number of cells in blastocysts in the SLC group, the Mini-SLC method is at least as good as swim-up for selecting frozen–thawed bull spermatozoa for in vitro fertilization (IVF). This method could potentially be used to prepare human sperm for assisted reproduction.