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.

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.

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.

The challenge of assisted reproduction for conservation of wild felids - A reality check.

Threats to the Earth's biodiversity are increasing exponentially, driven by human population growth and resource consumption. As many as one million wildlife species may disappear within the next few decades due to this human-induced extinction event. This represents our current reality and has profound implications for wildlife conservation. Within this context, application of assisted reproductive technology (ART) to conservation management is unlikely to mitigate broad-scale species loss, but for select species, such as wild cats, ART may determine if populations survive or disappear. In North American and European zoos, 20 of the world's 38 wild felid species are managed within structured breeding programs, but most are not sustainable with natural breeding alone. Zoo-based breeding programs are facing tenuous futures due to triage-based responses to this growing sustainability crisis. Theoretically, ART could benefit conservation management, but only by recognizing and addressing its present challenges. The application of ART to wildlife has been rarely successful, with only 62 mammal species (including 15 cat species) ever propagated by AI, and just 35 of these species (6 cats) reproduced following frozen semen AI. Even this most basic form of ART has a minimal impact on wildlife sustainability. The drivers of this deficit include lack of species-specific reproductive knowledge and limited access to animals for study, but also is exacerbated by a science-conservation disconnect that attempts to apply advanced reproductive technologies to species in which basic ART remains unproven. For a few felid species, these scientific challenges have been overcome and AI with frozen semen is becoming feasible as a practical management tool; for other felids, further research is needed. Non-scientific issues also impair our ability to use ART to implement global management plans. Political dysfunction, regulatory barriers and societal indifference create inertia that interferes with achieving meaningful progress in applying ART to wildlife. Collectively, these challenges may seem insurmountable but human resiliency is essential if we are to resolve these issues in a systematic manner. It will require expanding collaborative efforts substantially and intensifying efforts to conserve wildlife species that are literally running out of time. Our goal is to create a new reality that includes a sustainable future for wild felids and other imperiled wildlife species.

Recovering an endangered frog species through integrative reproductive technologies.

The establishment and management of ex situ breeding and assurance populations around the globe are meant to provide short-term solutions to the formidable loss of amphibian diversity presently occurring. Large multi-scaled facilities, such as zoos and aquariums, can provide the infrastructure to safeguard species and populations. However, often even large, economically viable facilities lack the knowledge to efficiently cater to the plethora of environmentally controlled physiological strategies that amphibians possess. Anurans present a class of amphibians that have often been viewed as easy to maintain ex situ. However, while adult survival may be relatively successful it is rarely accompanied by good reproductive output, health, and fitness. Even more conspicuous is the low survivorship of offspring produced ex situ once they are translocated back into the wild. The mountain yellow-legged frog (R. muscosa) ex situ breeding program EBP is a prime example of the challenges that amphibians EBPs face. Although more research is needed, the R. muscosa program has increased reproductive output and health of its colony by incorporating reproductive technologies and strategic genetic management in conjunction with a greater understanding of the species' natural history, to produce and translocate viable animals each year. This paper highlights the EBPs past decade of research featuring the program's contribution to building empirical, multidisciplinary approaches that boost the robustness of an endangered species, by safeguarding existing genetic diversity and maximizing fitness and survival outcomes.

Analysis of the impact of noninvasive prenatal testing for trisomies 21 and 18 in twin pregnancies undergoing artificial reproductive technology.

PURPOSE: The purpose of this study was to evaluate the performance and impact of noninvasive prenatal screening (NIPS) on twin pregnancies. PATIENTS AND METHODS: Twin pregnancies after artificial reproductive technology(ART) were tested by NIPS for screening trisomy 21, 18, and 13 in a single medical center in Hangzhou. Positive NIPS results were confirmed by karyotyping, while negative results were interviewed after delivery. RESULTS: From January 2019 to December 2020, 474 twin pregnancies were tested by NIPS for screening trisomy 21, 18, and 13 in a single medical center in Hangzhou. The performance of NIPS had been evaluated compared to the invasive diagnostic results. The positive predictive value (PPV) of NIPS for chromosome 21 and 18 aneuploidies is 80% (95CI, 36.09-96.59) and 100%, respectively. The incidence of trisomy 21, and 18 chromosome aneuploidies among the twin pregnancies undergoing ART was 0.84% and 0.21%, respectively. CONCLUSION: The performance of NIPS was substantially accurate among the twin pregnancies after ART in this study, and NIPS potentially avoided a considerable part of aneuploidies liveborn in twin pregnancies in Hangzhou.

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.

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.

Fertilizing morality: How religiosity and orientations toward science shape the morality, immorality, and amorality of reproductive technologies.

Scientific innovations continue to advance the possibilities of human reproduction, raising important empirical and ethical questions. In vitro fertilization, disease reproductive genetic technologies, and enhancement reproductive genetic technologies are three reproductive technologies with varying moral support. Instead of assuming moral poles, we use original, nationally representative survey data of US adults (N = 8107) and multinomial logistic regression to examine how religiosity and orientations toward science shape the moral acceptability, amorality, and the moral rejection of in vitro fertilization, disease reproductive genetic technologies, and enhancement reproductive genetic technologies. We find that increased confidence and trust in science lowered the odds of holding moral concerns, while greater religiosity was associated with higher odds of viewing these technologies as morally wrong. Moral attitudes further varied across religious tradition as certain religious groups had significantly higher odds of viewing these technologies as amoral. Findings have implications for advancing understandings of morality around the faith-science interface beyond conceptions of a moral binary.

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.

RUBIC (ReproUnion Biobank and Infertility Cohort): A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity.

BACKGROUND: Infertility affects 15%-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. OBJECTIVES: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up? MATERIAL AND METHODS: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.

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.

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.

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.

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.

Reproductive Technologies and Free Speech.

The Supreme Court and lower courts have not articulated a clear or consistent framework for First Amendment analysis of speech restrictions in health care and with respect to abortion. After offering a coherent doctrine for analysis of speech restrictions in the doctor-patient relationship, this piece demonstrates how potential legislation restricting patient access to information from reproductive testing intended to limit "undesirable" reproductive choices would violate the First Amendment.