Artificial Placenta Research Articles

Artificial uterus -research background to improve survival and outcome of extremely low birth weight newborns

In clinical research, of worldwide interest, some medical devices are being studied as a new reproductive technology, which can both guarantee the implantation of the embryo or support the premature newborn outside the maternal uterus (human and animal);

Ectogestation and the Problem of Abortion

Ectogestation involves the gestation of a fetus in an ex utero environment. The possibility of this technology raises a significant question for the abortion debate: Does a woman’s right to end her pregnancy entail that she has a right to the death of the fetus when ectogestation is possible? Some have argued that it does not Mathison & Davis (Bioeth 31:313–320, 2017). Others claim that, while a woman alone does not possess an individual right to the death of the fetus, the genetic parents have a collective right to its death Rasanen (Bioeth 31:697–702, 2017). In this paper, I argue that the possibility of ectogestation will radically transform the problem of abortion. The argument that I defend purports to show that, even if it is not a person, there is no right to the death of a fetus that could be safely removed from a human womb and gestated in an artificial womb, because there are competent people who are willing to care for and raise the fetus as it grows into a person. Thus, given the possibility of ectogestation, the moral status of the fetus plays no substantial role in determining whether there is a right to its death.

Artificial placenta and womb technology: Past, current, and future challenges towards clinical translation.

Extreme prematurity remains a major cause of neonatal mortality and severe long-term morbidity. Current neonatal care is associated with significant morbidity due to iatrogenic injury and developmental immaturity of extreme premature infants. A more physiologic approach, replacing placental function and providing a womb-like environment, is the foundational principle of artificial placenta (AP) and womb (AW) technology. The concept has been studied during the past 60 years with limited success. However, recent technological advancements and a greater emphasis on mimicking utero-placental physiology have improved the success of experimental models, bringing the technology closer to clinical translation. Here, we review the rationale for and history of AP and AW technology, discuss the challenges that needed to be overcome, and compare recent successful models. We conclude by outlining some remaining challenges to be addressed on the path towards clinical translation and opportunities for future research.

Reviewing the womb

Throughout most of human history women have been defined by their biological role in reproduction, seen first and foremost as gestators, which has led to the reproductive system being subjected...

Feasibility of Non-invasive Pulse Pressure Measurement Using the Phased-Tracking Method

Phased tracking (PT) is a high-precision ultrasonic technology that enables measurements of pulse pressure (PP). The aim of this study was to verify the accuracy of estimated PP using PT. Estimated PPs were compared with measured PPs in three sheep fetuses that were connected to an artificial placenta system. Similarly, estimated and measured PPs of 30 human neonates were compared. PP was calculated using the Water–Hammer equation (PP = ρ × PWV (pulse wave velocity) × ΔU). PWV was estimated by measuring the transit times of pulse waves at two sites along the aorta using the PT method, and ΔU was obtained by subtracting end-diastolic velocity from peak systolic velocity. The correlation between the estimated and measured PPs of the sheep fetuses was strong (r = 0.95, p ˂ 0.01), as was the case with the human neonates (r = 0.88, p ˂ 0.05). It can be concluded from the results of this study that PT may be a non-invasive alternative method used to predict PP.

Is 'viability' viable? Abortion, conceptual confusion and the law in England and Wales and the United States.

In this paper, I explore how viability, meaning the ability of the fetus to survive post-delivery, features in the law regulating abortion provision in England and Wales and the USA. I demonstrate that viability is formalized differently in the criminal law in England and Wales and the USA, such that it is quantified and defined differently. I consider how the law might be applied to the examples of artificial womb technology and anencephalic fetuses. I conclude that there is incoherence in the meaning of viability and argue that it is thus a conceptually illegitimate basis on which to ground abortion regulation. This is both because of the fluidity of the concept and because how it has been thus far understood in the law is unsupported by medical realities. Furthermore, it has the effect of heavily diluting pregnant people’s rights with overly moralistic limitations on access to healthcare.

Ectogenesis is for Feminists

In this critical perspective, I call for interdisciplinary feminist research to reclaim the subject of artificial womb technology from anti-abortion discourse. In 2017, scientists announced the successful animal trials of a highly advanced incubator that replicates the conditions of the uterus and was used to gestate lamb fetuses from the equivalent of approximately 22-24 weeks human gestation through to term in good health. This technology, now being prepared for human trials, has generated a new wave of research on ectogenesis, the process of gestating a pregnancy outside the body. But while ectogenesis raises many pressing ethical concerns, the discourse has frequently reverted to one claim: that by allowing the fetus to be removed from the pregnant person’s body without causing its death, ectogenesis will “solve” abortion. I argue that authors who make these claims fail to understand why feminists fight for abortion rights, take a narrow approach to reproductive freedom, neglect the social construction of “viability”, and fail to acknowledge the dependency of the fetus on care. Finally, I identify areas for future feminist intervention.

Gender, gestation and ectogenesis: self-determination for pregnant people ahead of artificial wombs

In this short response, I agree with Cavaliere’s recent invitation to consider ectogenesis, the process of gestation occurring outside the body, as a political perspective and provocation to building a...

Successful use of an artificial placenta–based life support system to treat extremely preterm ovine fetuses compromised by intrauterine inflammation

Exvivo uterine environment therapy is an experimental intensive care strategy for extremely preterm infants born between 21 and 24 weeks of gestation. Gas exchange is performed by membranous oxygenators connected by catheters to the umbilical vessels. The fetus is submerged in a bath of synthetic amniotic fluid. The lungs remain fluid filled, and pulmonary respiration does not occur. Intrauterine inflammation is strongly associated with extremely preterm birth and fetal injury. At present, there are no data that we are aware of to show that artificial placenta-based systems can be used to support extremely preterm fetuses compromised by exposure to intrauterine inflammation. To evaluate the ability of our exvivo uterine environment therapy platform to support extremely preterm ovine fetuses (95-day gestational age; approximately equivalent to 24 weeks of human gestation) exposed to intrauterine inflammation for a period of 120 hours, the following primary endpoints were chosen: (1) maintenance of key physiological variables within normal ranges, (2) absence of infection and inflammation, (3) absence of brain injury, and (4) gross fetal growth and cardiovascular function matching that of age-matched in utero controls. Ten ewes with singleton pregnancies were each given a single intraamniotic injection of 10-mg Escherichia coli lipopolysaccharides under ultrasound guidance 48 hours before undergoing surgical delivery for adaptation to exvivo uterine environment therapy at 95-day gestation (term=150 days). Fetuses were adapted to exvivo uterine environment therapy and maintained for 120 hours with constant monitoring of key vital parameters (exvivo uterine environment group) before being killed at 100-day equivalent gestational age. Umbilical artery blood samples were regularly collected to assess blood gas data, differential counts, biochemical parameters, inflammatory markers, and microbial load to exclude infection. Ultrasound was conducted at 48 hours after intraamniotic lipopolysaccharides (before surgery) to confirm fetal viability and at the conclusion of the experiments (before euthanasia) to evaluate cardiac function. Brain injury was evaluated by gross anatomic and histopathologic investigations. Eight singleton pregnant control animals were similarly exposed to intraamniotic lipopolysaccharides at 93-day gestation and were killed at 100-day gestation to allow comparative postmortem analyses (control group). Biobanked samples from age-matched saline-treated animals served as an additional comparison group. Successful instillation of lipopolysaccharides into the amniotic fluid exposure was confirmed by amniotic fluid analysis at the time of administration and by analyzing cytokine levels in fetal plasma and amniotic fluid. Data were tested for mean differences using analysis of variance. Six of 8 lipopolysaccharide control group (75%) and 8 of 10 exvivo uterine environment group fetuses (80%) successfully completed their protocols. Six of 8 exvivo uterine environment group fetuses required dexamethasone phosphate treatment to manage profound refractory hypotension. Weight and crown-rump length were reduced in exvivo uterine environment group fetuses at euthanasia than those in lipopolysaccharide control group fetuses (P<.05). There were no biologically significant differences in cardiac ultrasound measurement, differential leukocyte counts (P>.05), plasma tumor necrosis factor α, monocyte chemoattractant protein-1 concentrations (P>.05), or liver function tests between groups. Daily blood cultures were negative for aerobic and anaerobic growth in all exvivo uterine environment group animals. No cases of intraventricular hemorrhage were observed. White matter injury was identified in 3 of 6 lipopolysaccharide control group fetuses and 3 of 8 vivo uterine environment group fetuses. We report the use of an artificial placenta-based system to support extremely preterm lambs compromised by exposure to intrauterine inflammation. Our data highlight key challenges (refractory hypotension, growth restriction, and white matter injury) to be overcome in the development and use of artificial placenta technology for extremely preterm infants. As such challenges seem largely absent from studies based on healthy pregnancies, additional experiments of this nature using clinically relevant model systems are essential for further development of this technology and its eventual clinical application.

Neonatal incubator or artificial womb? Distinguishing ectogestation and ectogenesis using the metaphysics of pregnancy.

A 2017 Nature report was widely touted as hailing the arrival of the artificial womb. But the scientists involved claim their technology is merely an improvement in neonatal care. This raises an under-considered question: what differentiates neonatal incubation from artificial womb technology? Considering the nature of gestation-or metaphysics of pregnancy-(a) identifies more profound differences between fetuses and neonates/babies than their location (in or outside the maternal body) alone: fetuses and neonates have different physiological and physical characteristics; (b) characterizes birth as a physiological, mereological and topological transformation as well as a (morally relevant) change of location; and (c) delivers a clear distinction between neonatal incubation and ectogestation: the former supports neonatal physiology; the latter preserves fetal physiology. This allows a detailed conceptual classification of ectogenetive and ectogestative technologies according to which the 2017 system is not just improved neonatal incubation, but genuine ectogestation. But it is not an artificial womb, which is a term that is better put to rest. The analysis reveals that any ethical discussion involving ectogestation must always involve considerations of possible risks to the mother as well as her autonomy and rights. It also adds a third and potentially important dimension to debates in reproductive ethics: the physiological transition from fetus/gestateling to baby/neonate.

Willing mothers: ectogenesis and the role of gestational motherhood

While artificial womb technology (ectogenesis) is currently being studied for the purpose of improving neonatal care, I contend that this technology ought to be pursued as a means to address...

Artificial Wombs and the Ectogenesis Conversation: A Misplaced Focus? Technology, Abortion, and Reproductive Freedom

Bioethics scholarship considering the possibility of gestating an embryo to full term in an artificial womb (ectogenesis) often overstates the capacities of current technologies and underestimates the barriers to the development of full ectogenesis. Moreover, this debate causes harm by (1) neglecting more immediate problems in the development of artificial wombs, (2) treating abortion as a “problem with a technological solution,” bolstering anti-abortion rhetoric, and (3) presuming the stability of women’s reproductive rights. The ectogenesis conversation must consider anticipated uses of the technology (neonatal intensive care) and acknowledge the immediate context (recognizing abortion as essential healthcare and existing reproductive inequities).

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 Wombs Replace One Violence with Another

The serious concerns associated with abortion may have a technological solution. Artificial wombs, it is argued, offer a compromise to disburden woman of the bondage of pregnancy and to ensure the child’s survival. This essay argues against using artificial wombs to solve the abortion problem because using artificial wombs violates the principle of human embodiment. Artificial wombs cannot participate in the intimacy of human embodiment and therefore deprive the children of the intimacy of their embodiment.

Artificial Womb Technology and the Choice to Gestate Ex Utero: Is Partial Ectogenesis the Business of the Criminal Law?

It is frequently claimed that artificial wombs (AWs) could alleviate the burdens placed exclusively on women in reproduction. In this article, I demonstrate how AWs used for the partial gestation of preterm neonates could introduce new choices for women by changing perceptions of tolerable risks in gestation. In light of advancing medical technology, it is necessary to consider whether the current legal framework in England and Wales would support increased choice for women about alternative forms of gestation. I examine the ill-defined offence of ‘unlawfully procuring miscarriage’ in the Offences Against the Person Act 1861 and demonstrate that different conclusions about the legal significance of ending a pregnancy are evident, depending on the analytical lens adopted in interpreting ambiguities. Furthermore, I demonstrate that the defences available to pregnancy termination under the Abortion Act 1967 are too narrow to support choices about alternative forms of gestation, even if they become physically and medically possible. Therefore, we should decriminalise termination of pregnancy, or, if it is assumed that gestation is the business of the criminal law, specific reforms to the legal framework are necessary. The offence of unlawfully procuring miscarriage is too uncertain and broad, and the defences available are too restrictive.

Developmental status and prospect of artificial placenta

Extremely premature infants(EPI), especially those under 25 weeks of gestational age, are difficult to manage clinically and have high mortality and disability rates.It is difficult to solve the bottleneck problem fundamentally in the treatment of EPI.Artificial placenta is a fascinating alternative therapy for neonatal lung failure and is expected to maintain the normal development of EPI after delivery.This article briefly introduces the research history, current situation, difficulties to be overcome and future prospects of artificial placenta. Key words: Extremely premature infant; Treatment; Artificial placenta; Prognosis

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.

Artificial wombs, birth and ‘birth’: a response to Romanis

Recently, I argued that human subjects in artificial wombs (AWs) ‘share the same moral status as newborns’ and so, deserve the same treatment and protections as newborns. This thesis rests...

Tidal Flow Perfusion for the Artificial Placenta: A Paradigm Shift.

The modalities of vascular access for the extracorporeal artificial placenta (AP) have undergone many iterations over the past decade. We hypothesized that single lumen cannulation (SLC) of the jugular vein using tidal flow extracorporeal life (ECLS) support is a feasible alternative to venovenous (VV) umbilical-jugular cannulation and double lumen cannulation (DLC) and can maintain fetal circulation, stable hemodynamics, and adequate gas exchange for 24 hours. After in vitro evaluation of the tidal flow system, six preterm lambs at estimated gestational age 118-124 days (term 145 days) were delivered and underwent VV-ECLS. Three were supported using DLC and three with SLC utilizing tidal flow AP support. Hemodynamics, circuit flow, and gas exchange were monitored. Target fetal parameters were as follows: mean arterial pressure 40-60 mmHg, heart rate 140-240 beats per minute (bpm), SatO2% 60-80%, PaO2 25-50 mmHg, PaCO2 30-55 mmHg, oxygen delivery >5 ml O2/dl/kg/min, and circuit flow 100 ± 25 ml/kg/min. All animals survived 24 hours and maintained fetal circulation with stable hemodynamics and adequate gas exchange. Parameters of the tidal flow group were comparable with those of DLC. Single lumen jugular cannulation using tidal flow is a promising vascular access strategy for AP support. Successful miniaturization holds great potential for clinical translation to support extremely premature infants.

Ex Utero Extracorporeal Support as a Model for Fetal Hypoxia and Brain Dysmaturity

Congenital heart disease (CHD) is associated with abnormal fetal brain development, a phenomenon that may be related to decreased cerebral oxygen delivery in utero. We used an artificial womb model to test the hypothesis that decreasing fetal oxygen delivery would reproduce physiologic changes identified in fetuses with CHD. Experimental (hypoxemic) fetal lambs (mean gestational age, 111 ± 3 days; n= 4) and control animals (112 days; n= 5) were maintained in the artificial womb for a mean of 22 ± 6 days. Oxygen delivery was reduced to 15.6 ± 1.0 mL/kg/min in the hypoxemia animals versus 21.6 ± 2.0 mL/kg/min in the control animals. Blood chemistry analysis and sonographic evaluation were performed daily. An additional control group (n= 7) was maintained in utero and harvested for analysis at gestational age 134 ± 4 days. Physiologic variables were monitored continuously, and no statistical differences between the groups were identified. Fetal oxygen delivery and arterial partial pressure of oxygen were remarkably lower in the experimental group longitudinally. Increased umbilical artery and decreased middle cerebral artery resistance resulted in a lower cerebral to umbilical resistance ratio, similar to the brain sparing effect observed in human fetuses with CHD. Experimental brains were smaller than control brains in relation to the calvarium on magnetic resonance. Sustained hypoxemia in fetal sheep leads to altered cerebrovascular resistances and loss of brain mass, similar to human fetuses with CHD. This unique model provides opportunities to investigate the pathologic process underlying CHD-associated brain dysmaturity and to evaluate potential fetal neuroprotective therapies.