Whose (germ) line is it anyway? Reproductive technologies and kinship.

Reproductive biotechnologies can separate concepts of parenthood into genetic, gestational and social dimensions, often leading to a fragmentation of heteronormative kinship models and posing a challenge to historical methods of establishing legal and/or moral parenthood. Using fictional cases, this article will demonstrate that the issues surrounding the intersection of current and emerging reproductive biotechnologies with definitions of parenthood are already leading to confusion regarding social and legal family ties for offspring, which is only expected to increase as new technologies develop. Rather than opposing these new technologies to reassert traditional concepts of the family, however, this article will explore the opportunities that these technologies represent for re-imagining various culturally cherished values of family-making in a way that is inclusive of diverse genders, sexualities and cultures. It will consider IVF, gametogenesis, mitochondrial donation, surrogacy, artificial gestation, CRISPR-Cas9 gene editing, foster care and adoption as some of many possible pathways to parenthood, including for members of the LGBTIAUQ+ community.

Near-Infrared-Driven Nanorocket for Rapid and Ultrasensitive Detection of MicroRNA.

Herein, by introducing gold nanostars (AuNSs) as fuel core, a near-infrared-driven nanorocket (NIDNR) with pretty fast walking was exploited for ultrasensitive miRNA detection. Compared with traditional nanomaterials-comprised nanomachines (NMs), the NIDNR possesses much better kinetic and thermodynamic performance owing to the extra photothermal driving force from localized surface plasmon (LSP). Impressively, the whole reaction time of NIDNR down to 15 min was realized, which is almost more than 8 times beyond those of conventional DNA-based NMs. This way, the inherent obstacle of traditional NMs, including long reaction time and low efficiency, could be easily addressed. As a proof of concept, the NIDNR was successfully applied to develop an electrochemical biosensing platform for rapid and sensitive detection of miRNA with an LOD down to 2.95 aM and achieved the real-time assay of real biological samples from human hepatocellular carcinoma cells (MHCC97L) and HeLa, thus providing an innovative insight to design more versatile DNA nanomachines for ultimate application in biosensing platform construction and clinical sample detection.

Alterations in the expression pattern of some epigenetic-related genes and microRNAs subsequent to oocyte cryopreservation.

MicroRNAs (miRNAs) are small non-encoding RNAs that actively regulate biological and physiological processes, and play an important role in regulating gene expression in all cells, especially in most animal cells, including oocytes and embryos. The expression of miRNAs at the right time and place is crucial for the oocyte's maturation and the embryo's subsequent development. Although assisted reproductive techniques (ART) have helped to solve many infertility problems, they cause changes in the expression of miRNA and genes in oocytes and preimplantation embryos, and the effect of these changes on the future of offspring is unknown, and has caused concerns. The relevant genomic alterations commonly imposed on embryos during cryopreservation may have potential epigenetic risks. Understanding the biological functions of miRNAs in frozen maturated oocytes may provide a better understanding of embryonic development and a comparison of fertility conservation in female mammals. With the development of new techniques for genomic evaluation of preimplantation embryos, it has been possible to better understand the effects of ART. The results of various articles have shown that freezing of oocytes and the cryopreservation method are effective for the expression of miRNAs and, in some cases, cause changes in the expression of miRNAs and epigenetic changes in the resulting embryo. This literature review study aimed to investigate the effects of oocyte cryopreservation in both pre-maturation and post-maturation stages, the cryopreservation method and the type of cryoprotectants (CPA) used on the expression of some epigenetic-related genes and miRNAs.

Metabolic Mechanisms and Potential Therapeutic Targets for Prevention of Ovarian Aging: Data from Up-to-Date Experimental Studies.

Female infertility and reproduction is an ongoing and rising healthcare issue, resulting in delaying the decision to start a family. Therefore, in this review, we examine potential novel metabolic mechanisms involved in ovarian aging according to recent data and how these mechanisms may be addressed through new potential medical treatments. We examine novel medical treatments currently available based mostly on experimental stem cell procedures as well as caloric restriction (CR), hyperbaric oxygen treatment and mitochondrial transfer. Understanding the connection between metabolic and reproductive pathways has the potential to offer a significant scientific breakthrough in preventing ovarian aging and prolonging female fertility. Overall, the field of ovarian aging is an emerging field that may expand the female fertility window and perhaps even reduce the need for artificial reproductive techniques.

Human Germline Genome Editing: On the Nature of Our Reasons to Genome Edit.

Ever since the publication of Derek Parfit's Reasons and Persons, bioethicists have tended to distinguish between two different ways in which reproductive technologies may have implications for the welfare of future persons. Some interventions harm or benefit particular individuals: they are "person affecting." Other interventions determine which individual, of a number of possible individuals, comes into existence: they are "identity affecting" and raise the famous "non-identity problem." For the past several decades, bioethical debate has, for the most part, proceeded on the assumption that direct genetic modification of human embryos would be person affecting. In this paper, I argue that that genome editing is highly unlikely to be person affecting for the foreseeable future and, as a result, will neither benefit nor harm edited individuals.

The limitations of liberal reproductive autonomy.

The common liberal understanding of reproductive autonomy - characterized by free choice and a principle of non-interference - serves as a useful way to analyse the normative appeal of having certain choices open to people in the reproductive realm, especially for issues like abortion rights. However, this liberal reading of reproductive autonomy only offers us a limited ethical understanding of what is at stake in many kinds of reproductive choices, particularly when it comes to different uses of reproductive technologies and third-party reproduction. This is because the liberal framework does not fully capture who benefits from which reproductive options, the extent of the risks and harms involved in various reproductive interventions, and the reasons for why people are driven to make certain reproductive choices.

The European Court of Human Rights and the Emergence of Human Germline Genome Editing.

The field of human germline genome editing (HGGE) offers a promising reproductive potential to prevent inheritance of genetic diseases, yet also opens the door to undesirable eugenics. This stirred the debate about the acceptability of HGGE in light of human rights, particularly human dignity. The European Convention of Human Rights (ECHR) and the European Court of Human Rights (ECtHR) use human dignity as a guiding principle. Therefore, this article examined the clinical implementation of HGGE in light of relevant case-law regarding Article 2 and Article 8 ECHR. The analysis illustrates that the ECtHR broadens the scope of artificial reproductive rights under Article 8, however, Contracting States of the Council of Europe can limit these rights and the accessibility to reproductive techniques, such as HGGE. The ECtHR remains elusive about the legal status of unborn life, but protection under Article 2 with the introduction of HGGE should not be ruled out.

Progress and challenges in developing organoids in farm animal species for the study of reproduction and their applications to reproductive biotechnologies.

Within the past decades, major progress has been accomplished in isolating germ/stem/pluripotent cells, in refining culture medium and conditions and in establishing 3-dimensional culture systems, towards developing organoids for organs involved in reproduction in mice and to some extent in humans. Haploid male germ cells were generated in vitro from primordial germ cells. So were oocytes, with additional support from ovarian cells and subsequent follicle culture. Going on with the female reproductive tract, spherical oviduct organoids were obtained from adult stem/progenitor cells. Multicellular endometrial structures mimicking functional uterine glands were derived from endometrial cells. Trophoblastic stem cells were induced to form 3-dimensional syncytial-like structures and exhibited invasive properties, a crucial point for placentation. Finally, considering the embryo itself, pluripotent embryonic cells together with additional extra-embryonic cells, could self-organize into a blastoid, and eventually into a post-implantation-like embryo. Most of these accomplishments have yet to be reached in farm animals, but much effort is devoted towards this goal. Here, we review the progress and discuss the specific challenges of developing organoids for the study of reproductive biology in these species. We consider the use of such organoids in basic research to delineate the physiological mechanisms involved at each step of the reproductive process, or to understand how they are altered by environmental factors relevant to animal breeding. We evaluate their potential in reproduction of animals with a high genetic value, from a breeding point of view or in the context of preserving local breeds with limited headcounts.

Ethics and animal reproductive technologies.

This paper offers a framework to help animal scientists engage in critical thinking about their own practices. Its objective is to reinforce their ability to participate in debates and discussions about the ethics surrounding the use of modern animal reproductive technologies (ART). This will be achieved first by exploring some of the most important philosophical conceptualizations of animals in Western philosophy, which are shaping the way humans interact with them. Then, we will analyse whether modern ART constitute ethically significant innovations in comparison with more traditional animal breeding practices, or whether they stand in continuity with the latter. This will be followed by a review some of the most important ethical issues with modern ART, where human, animal welfare, environmental and socio-economic issues will be discussed.

Molecular diagnosis of SARS-CoV-2 in seminal fluid.

PURPOSE: Due to relevant repercussions on reproductive medicine, we aimed to evaluate feasibility of RT-PCR as a detection method of SARS-CoV-2 RNA in seminal fluid. METHODS: A qualitative determination of the RT-PCR assays in semen was performed through different approaches: (1) efficiency of RNA extraction from sperm and seminal plasma was determined using PRM1 and PRM2 mRNA and a heterologous system as control; (2) samples obtained by diluting viral preparation from a SARS-CoV-2 panel (virus cultured in Vero E6 cell lines) were tested; (3) viral presence in different fractions of seminal fluid (whole sample, seminal plasma and post-centrifugation pellet) was evaluated. Semen samples from mild and recovered COVID-19 subjects were collected by patients referring to the Infectious Disease Department of the Policlinico Umberto I Hospital - "Sapienza" University of Rome. Control subjects were recruited at the Laboratory of Seminology-Sperm Bank "Loredana Gandini'' of the same hospital. RESULTS: The control panel using viral preparations diluted in saline and seminal fluid showed the capability to detect viral RNA presence with Ct values depending on the initial viral concentration. All tested semen samples were negative for SARS-CoV-2, regardless of the nasopharyngeal swab result or seminal fluid fraction. CONCLUSION: These preliminary data show that RT-PCR for SARS-CoV-2 RNA testing appears to be a feasible method for the molecular diagnosis of SARS-CoV-2 in seminal fluid, supported by results of the control panel. The ability to detect SARS-CoV-2 in semen is extremely important for reproductive medicine, especially in assisted reproductive technology and sperm cryopreservation.

Expanded carrier screening for recessively inherited disorders: economic burden and factors in decision-making when one individual in a couple is identified as a carrier.

PURPOSE: When undergoing expanded carrier screening (ECS), couples are often screened sequentially to reduce need for a second individual's test. It is unknown how often partners of individuals found to be carriers complete the recommended testing with a sequential approach and what factors contribute to decision-making regarding partner testing. Additionally, the economic burden placed on individuals by ECS testing and its effect on partner testing has not been evaluated. METHODS: In part 1, all individuals at a university-affiliated reproductive endocrinology and infertility practice identified to be carriers of a recessively inherited mutation using the Counsyl/Foresight ECS were included. Conditions were categorized by severity according to a previously described classification system. In part 2, all individuals who underwent ECS with a single test provider between September 1, 2013 and February 1, 2020 were contacted via email to complete a confidential and anonymized online survey. RESULTS: In part 1, a total of 2061 patients were screened. 36.9% were carriers of one or more recessively inherited disorders. Twenty-seven percent of positively screened individuals did not have their partner screened. Carriers of a moderate condition had a trend towards a reduced odds for having their partner screened compared to a profound condition (OR 0.36, 95% CI 0.12-1.05, p = 0.06). Number of conditions was not predictive of subsequent partner screening (OR 0.95, 95% CI 0.72-1.25, p = 0.72). In part 2, the cost of ECS was not covered by insurance for 54.5% (103/189) and most paid over $300 out-of-pocket for testing (47.6%). The most common reason for not completing partner testing was that the results would not alter their course when seeking conception (33.3%). 73.5% of patients knew that the largest benefit of ECS comes from knowing a partner's results as well as their own. CONCLUSIONS: Not all carriers of recessively inherited disorders choose to undergo partner screening. Patients found to be carrier of more debilitating genetic disorders may be more likely to screen their reproductive partners. For many, ECS testing is not covered by insurance, and this test may impose a significant economic burden. For some patients, the results of ECS would not change what they would do when seeking conception. Providers should evaluate whether a patient's ECS result would change their treatment course prior to testing.

Fertility and reproductive technology use in testicular cancer survivors in Japan: A multi-institutional, cross-sectional study.

OBJECTIVE: To evaluate fertility and use of reproductive technology of testicular cancer survivors in a multi-institutional, cross-sectional study. METHODS: This study recruited testicular cancer survivors who were followed after treatment for testicular cancer at eight high-volume institutions between 2018 and 2019. The participants completed the questionnaires on marital status, fertility and use of reproductive technology. RESULTS: A total of 567 testicular cancer survivors, with a median age of 43 years, responded to the questionnaire. Chemotherapy was given to 398 survivors, including three cycles of cisplatin-based chemotherapy in 106 patients and four cycles in 147 patients. Among 153 survivors who attempted sperm cryopreservation, 133 (87%) could preserve sperm. Of the 28 survivors whose cryopreserved sperm was used, 17 (61%) fathered children. Of the 72 survivors who fathered children without the use of cryopreserved sperm, 59 (82%) fathered naturally. Whereas 33 (20%) of 169 survivors treated without chemotherapy fathered children without using cryopreserved sperm, 39 (10%) of 398 treated with chemotherapy fathered children (P < 0.05). Furthermore, the paternity rate was 12% and 5% in testicular cancer survivors with three and four cycles of cisplatin-based chemotherapy, respectively (P < 0.05). However, of 121 survivors who wanted to have children, 14 (12%) received counseling about infertility treatment. CONCLUSIONS: Testicular cancer survivors preserving their sperm have a higher paternity rate after chemotherapy, especially after four cycles, than those not using cryopreserved sperm. Physicians who give chemotherapy for testicular cancer need to take particular care not only with respect to recurrence of testicular cancer, but also to post-treatment fertility.

Infertility policy analysis: a comparative study of selected lower middle- middle- and high-income countries.

BACKGROUND: Infertility has recently become a salient but neglected global issue. Policies to address the sexual and reproductive health and rights (SRHR) are vital, especially in lower middle and middle-income countries (LMICs). Hence, the aim of this study was to compare the national infertility policies in the selected countries (LMICs comparing with high-income) to determine gaps or to confirm desirable policies in the given health systems. METHODS: This study has executed a comparative policy analysis of infertility services using the universal health coverage framework (financial protection, population coverage, and service features) in three scopes (prevention, treatment, and supportive care). Seven countries that had infertility programs in their health sectors were selected. RESULTS: The results showed that financial protection was good in high and middle-income countries, but in a lower middle income, and in one high-income country was poor. The findings also showed that health systems in the same countries had no infertility services for men. Preventive and supportive care services were neglected in LMICs by governments. CONCLUSION: The findings indicate that income is not the only factor that fulfills universal health coverage for infertility care services. Perhaps to achieve equity in infertility care services, it should be seen as a universal human right to accomplish the right to have a child and to have a life with physical and mental health for all men and women.

Gestation, equality and freedom: ectogenesis as a political perspective.

The benefits of full ectogenesis, that is, the gestation of human fetuses outside the maternal womb, for women ground many contemporary authors' arguments on the ethical desirability of this practice. In this paper, I present and assess two sets of arguments advanced in favour of ectogenesis: arguments stressing ectogenesis' equality-promoting potential and arguments stressing its freedom-promoting potential. I argue that although successfully grounding a positive case for ectogenesis, these arguments have limitations in terms of their reach and scope. Concerning their limited reach, I contend that ectogenesis will likely benefit a small subset of women and, arguably, not the group who most need to achieve equality and freedom. Concerning their limited scope, I contend that these defences do not pay sufficient attention to the context in which ectogenesis would be developed and that, as a result, they risk leaving the status quo unchanged. After providing examples of these limitations, I move to my proposal concerning the role of ectogenesis in promoting women's equality and freedom. This proposal builds on Silvia Federici's, Mariarosa Dalla Costa's and Selma James' readings of the international feminist campaign 'Wages for Housework'. It maintains that the political perspective and provocation that ectogenesis can advance should be considered and defended.

Abortion and Ectogenesis: Moral Compromise.

The contemporary philosophical literature on abortion primarily revolves around three seemingly intractable debates, concerning the (1) moral status of the fetus, (2) scope of women's rights and (3) moral relevance of the killing/letting die distinction. The possibility of ectogenesis-technology that would allow a fetus to develop outside of a gestational mother's womb-presents a unique opportunity for moral compromise. Here, I argue those opposed to abortion have a prima facie moral obligation to pursue ectogenesis technology and provide ectogenesis for disconnected fetuses as part of a moral compromise.

Procreation machines: Ectogenesis as reproductive enhancement, proper medicine or a step towards posthumanism?

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.

Artificial womb technology and clinical translation: Innovative treatment or medical research?

In 2017 and 2019, two research teams claimed 'proof of principle' for artificial womb technology (AWT). AWT has long been a subject of speculation in bioethical literature, with broad consensus that it is a welcome development. Despite this, little attention is afforded to more immediate ethical problems in the development of AWT, particularly as an alternative to neonatal intensive care. To start this conversation, I consider whether experimental AWT is innovative treatment or medical research. The research-treatment distinction, pervasive in regulation worldwide, is intended to isolate research activities and subject them to a greater degree of oversight. I argue that there is a tendency in the literature to conceptualize AWT for partial ectogenesis as innovative treatment. However, there are sufficiently serious ethical concerns with experimental AWT that mean that it must not be first used on humans on the basis that it is a 'beneficial treatment'. First, I outline the prospects for translation of AWT animal studies into treatment for human preterms. Second, I challenge the conceptualizations of experimental AWT as innovative treatment. It must be considered medical research to reflect the investigatory nature of the process and guarantee sufficient protections for subjects. Identifying that AWT is research is crucial in formulating further ethico-legal questions regarding the experimental use of AWT. Third, I demonstrate that clinical trials will be a necessary part of the clinical translation of AWT because of requirements laid out by regulators. I consider the justification for clinical trials and highlight some of the crucial ethical questions about the conditions under which they should proceed.

Hormonal Effects in Reproductive Technology with Focus on Diminished Ovarian Reserve.

Modern use of reproductive technologies has revolutionized the treatment of infertile couples. Strategies to improve ovarian function in cases of diminished ovarian reserve are perhaps the least understood area in this field and will be the chief focus of this chapter.

Lessons learned from the Czech uterus transplant trial related to surgical technique that may affect reproductive success.

Uterus transplantation is an experimental method in the treatment of infertility in women with congenital or acquired absence of uterus. The majority of uterus transplants worldwide have been performed in women with Mayer-Rokitansky-Küster-Hauser syndrome, with neovagina and absent uterus. We report two aspects affecting reproductive success related to the surgical technique of transplantation. The first is the stenosis of vaginal-neovaginal anastomosis between the graft's vaginal rim and the recipient's neovagina. The second is a firm fixation of the uterus close to the pubic symphysis. Both these aspects contribute to the technical difficulty of embryo transfer to the transplanted uterus.

Beyond pathology: women's lived experiences of melancholy and mourning in infertility treatment.

Throughout history, melancholy and mourning are predominantly understood within the tradition of psychopathology. Herein, melancholy is perceived as an ailing response to significant loss, and mourning as a healing experience. By taking the philosophies of Freud, Ricoeur and Kristeva together with relevant social scientific research as a theoretical framework and by drawing on women's accounts of melancholy and mourning in infertility treatment, we offer an exploration of melancholy and mourning beyond this pathological ailing/healing logic. We do so by asking what it means for women to actually live with melancholy and mourning in infertility treatment. In answering this question, we show that women in infertility treatment may have different kinds of melancholic longings: they desire their lost time as a pregnant woman, lost love life and lost future. Within these longings, women derive their sense of self predominantly from their lost past: they understand themselves as the mothers or lovers they once were or could have been. We further reveal that some of these women attempt to escape this dwelling of identity and mourn their losses by (re)narrating their pasts or through performing rituals. While these results show how melancholy and mourning are coshaped in relation to these women's embodied, temporal, sociocultural and material lived context, they also give insight into how melancholy and mourning may be understood beyond infertility treatment. We reveal how the binary dynamic between melancholy and mourning is inherently ambiguous: melancholy instigates a joyous painfulness, something that is or is not overcome through the agonising exertion of mourning. We show, moreover, that underlying this melancholy/mourning dynamic is a pressing and uncontrollable reality of not being able to make (sufficient) sense of oneself. At the end of this work, then, we argue that it follows out of these conclusions' urgency to have context-sensitive compassionate patience with those who live with melancholy and mourning.