Artificial womb

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Artificial womb
Figure from a 2017 Nature Communications paper describing an extra-uterine life support system, or "biobag", used to grow lamb fetuses. Nature Communications Biobag system design.jpg
Figure from a 2017 Nature Communications paper describing an extra-uterine life support system, or "biobag", used to grow lamb fetuses.

An artificial womb or artificial uterus is a device that would allow for extracorporeal pregnancy, [2] by growing a fetus outside the body of an organism that would normally carry the fetus to term. [3] An artificial uterus, as a replacement organ, would have many applications. It could be used to assist male or female couples in the development of a fetus. [2] This can potentially be performed as a switch from a natural uterus to an artificial uterus, thereby moving the threshold of fetal viability to a much earlier stage of pregnancy. [2] In this sense, it can be regarded as a neonatal incubator with very extended functions. It could also be used for the initiation of fetal development. [2] An artificial uterus could also help make fetal surgery procedures at an early stage an option instead of having to postpone them until term of pregnancy. [2]

Contents

In 2016, scientists published two studies regarding human embryos developing for thirteen days within an ecto-uterine environment. [4] [5] In 2017, fetal researchers at the Children's Hospital of Philadelphia published a study showing they had grown premature lamb fetuses for four weeks in an extra-uterine life support system. [1] [6] [7] A 14-day rule prevents human embryos from being kept in artificial wombs longer than 14 days; this rule has been codified into law in twelve countries. [8] In 2021, The Washington Post reported that "the International Society for Stem Cell Research relaxed a historical '14-day rule' that said researchers could grow natural embryos for only 14 days in the laboratory, allowing researchers to seek approval for longer studies"; but the article nonetheless specified that: "[h]uman embryo models are banned from being implanted into a uterus." [9]

Components

An artificial uterus, sometimes referred to as an "exowomb", [10] would have to provide nutrients and oxygen to nurture a fetus, as well as dispose of waste material. The scope of an artificial uterus, or "artificial uterus system" to emphasize a broader scope, may also include the interface serving the function otherwise provided by the placenta, an amniotic tank functioning as the amniotic sac, as well as an umbilical cord.

Nutrition, oxygen supply and waste disposal

A woman may still supply nutrients and dispose of waste products if the artificial uterus is connected to her. [2] She may also provide immune protection against diseases by passing of IgG antibodies to the embryo or fetus. [2]

Artificial supply and disposal have the potential advantage of allowing the fetus to develop in an environment that is not influenced by the presence of disease, environmental pollutants, alcohol, or drugs which a human may have in the circulatory system. [2] There is no risk of an immune reaction towards the embryo or fetus that could otherwise arise from insufficient gestational immune tolerance. [2] Some individual functions of an artificial supplier and disposer include:

Theoretically, animal suppliers and disposers may be used, but when involving an animal's uterus the technique may rather be in the scope of interspecific pregnancy.[ original research? ]

Uterine wall

In a normal uterus, the myometrium of the uterine wall functions to expel the fetus at the end of a pregnancy, and the endometrium plays a role in forming the placenta. An artificial uterus may include components of equivalent function. Methods have been considered to connect an artificial placenta and other "inner" components directly to an external circulation. [2]

Interface (artificial placenta)

An interface between the supplier and the embryo or fetus may be entirely artificial, e.g. by using one or more semipermeable membranes such as is used in extracorporeal membrane oxygenation (ECMO). [11]

There is also potential to grow a placenta using human endometrial cells. In 2002, it was announced that tissue samples from cultured endometrial cells removed from a human donor had successfully grown. [15] [16] The tissue sample was then engineered to form the shape of a natural uterus, and human embryos were then implanted into the tissue. The embryos correctly implanted into the artificial uterus' lining and started to grow. However, the experiments were halted after six days to stay within the permitted legal limits of in vitro fertilisation (IVF) legislation in the United States. [2]

A human placenta may theoretically be transplanted inside an artificial uterus, but the passage of nutrients across this artificial uterus remains an unsolved issue. [2]

Amniotic tank (artificial amniotic sac)

The main function of an amniotic tank would be to fill the function of the amniotic sac in physically protecting the embryo or fetus, optimally allowing it to move freely. It should also be able to maintain an optimal temperature. Lactated Ringer's solution can be used as a substitute for amniotic fluid. [11]

Umbilical cord

Theoretically, in case of premature removal of the fetus from the natural uterus, the natural umbilical cord could be used, kept open either by medical inhibition of physiological occlusion, by anti-coagulation as well as by stenting or creating a bypass for sustaining blood flow between the mother and fetus. [2]

Research and development

The use of artificial wombs was first termed ectogenesis by British-Indian pioneer JBS Haldane in 1923. [17] [18] [19] [20]

Specifying related terminology, one paper determines:

"A potential, though remotely possible, application of the technology is ‘complete ectogenesis’ – complete gestation outside the human body. This will greatly affect the substantiated human involvement during gestation, making it an extracorporeal event and thus completely transforming the conventional notion of pregnancy." [21]

Emanuel M. Greenberg (USA)

Emanuel M. Greenberg wrote various papers[ clarification needed ] on the topic of the artificial womb and its potential use in the future. [22]

On 22 July 1954 Emanuel M. Greenberg filed a patent on the design for an artificial womb. [23] The patent included two images of the design for an artificial womb. The design itself included a tank to place the fetus filled with amniotic fluid, a machine connecting to the umbilical cord, blood pumps, an artificial kidney, and a water heater. He was granted the patent on 15 November 1955. [23]

Juntendo University (Japan)

In 1996, Juntendo University in Tokyo developed the extra-uterine fetal incubation (EUFI). [24] The project was led by Yoshinori Kuwabara, who was interested in the development of immature newborns. The system was developed using fourteen goat fetuses that were then placed into artificial amniotic fluid under the same conditions of a mother goat. [24] [25] Kuwabara and his team succeeded in keeping the goat fetuses in the system for three weeks. [24] [25] The system, however, ran into several problems and was not ready for human testing. [24] Kuwabara remained hopeful that the system would be improved and would later be used on human fetuses. [24] [25]

Children's Hospital of Philadelphia

In 2017, researchers at the Children's Hospital of Philadelphia were able to further develop the extra-uterine system. The study uses fetal lambs which are then placed in a plastic bag filled with artificial amniotic fluid. [1] [7] The system consist in 3 main components: a pumpless arteriovenous circuit, a closed sterile fluid environment and an umbilical vascular access. Regarding the pumpless arteriovenous circuit, the blood flow is driven exclusively by the fetal heart, combined with a very low resistance oxygenator to most closely mimic the normal fetal/placental circulation. The closed sterile fluid environment is important to ensure sterility. Scientists developed a technique for umbilical cord vessel cannulation that maintains a length of native umbilical cord (5–10 cm) between the cannula tips and the abdominal wall, to minimize decannulation events and the risk of mechanical obstruction. [26] The umbilical cord of the lambs are attached to a machine outside of the bag designed to act like a placenta and provide oxygen and nutrients and also remove any waste. [1] [7] The researchers kept the machine "in a dark, warm room where researchers can play the sounds of the mother's heart for the lamb fetus." [7] The system succeeded in helping the premature lamb fetuses develop normally for a month. [7] Indeed, scientists have run 8 lambs with maintenance of stable levels of circuit flow equivalent to the normal flow to the placenta. Specifically, they have run 5 fetuses from 105 to 108 days of gestation for 25–28 days, and 3 fetuses from 115 to 120 days of gestation for 20–28 days. The longest runs were terminated at 28 days due to animal protocol limitations rather than any instability, suggesting that support of these early gestational animals could be maintained beyond 4 weeks. [26] Alan Flake, a fetal surgeon at the Children's Hospital of Philadelphia hopes to move testing to premature human fetuses, but this could take anywhere from three to five years to become a reality. [7] Flake, who led the study, calls the possibility of their technology recreating a full pregnancy a "pipe dream at this point" and does not personally intend to create the technology to do so. [7]

Colossal Biosciences

In 2021, a start-up company founded by Benn Lamm and Church Hill, Colossal Biosciences began research and development of artificial animal wombs to further de-extinction and conservation efforts for species such as the woolly mammoth and northern white rhinoceros. [27] An artificial womb is also necessary in reviving a species with no suitable living surrogate species such as Steller's sea cow or elephant bird [28] Colossal in collaboration with the University of Melbourne have also developed artificial marsupial pouches as part of their de-extinction project of the thylacine. [29]

Eindhoven University of Technology (NL)

Since 2016, researchers of TU/e and partners aim to develop an artificial womb, which is an adequate substitute for the protective environment of the maternal womb in case of premature birth, preventing health complications. The artificial womb and placenta will provide a natural environment for the baby with the goal to ease the transition to newborn life. The perinatal life support (PLS) system will be developed using breakthrough technology: a manikin will mimic the infant during testing and training, advanced monitoring and computational modeling will provide clinical guidance. [30]

The consortium of 3 European universities working on the project consists out of Aachen, Milaan and Eindhoven. In 2019 this consortium was granted a subsidy of 3 million euros, and a second grant of 10 million is in progress. Together, the PLS partners provide joint medical, engineering, and mathematical expertise to develop and validate the Perinatal Life Support system using breakthrough simulation technologies. The interdisciplinary consortium will push the development of these technologies forward and combine them to establish the first ex vivo fetal maturation system for clinical use. This project, coordinated by the Eindhoven University of Technology brings together world-leading experts in obstetrics, neonatology, industrial design, mathematical modelling, ex vivo organ support, and non-invasive fetal monitoring. This consortium is led by professor Frans van de Vosse and Professor and doctor Guid Oei. in 2020 the spin off Juno Perinatal Healthcare has been set up by engineers Jasmijn Kok and Lyla Kok, assuring valorisation of the research done. More information about the spin off can be found here; [31]

More information about the project of the technical universities and its researchers can be found here: [32]

Weizmann Institute of Science (Israel)

Electronically controlled ex utero roller culture system (technical steps during sEmbryo culture protocol) Images representing technical steps during sEmbryo culture protocol.jpg
Electronically controlled ex utero roller culture system (technical steps during sEmbryo culture protocol)

In 2021, the Weizmann Institute of Science in Israel built a mechanical uterus and grew mouse embryos outside the uterus for several days. [33] This device was also used in 2022 to nurture mouse stem cells for over a week and grow synthetic embryos from stem cells. [34] [35]

Philosophical considerations

Bioethics

The development of artificial uteri and ectogenesis raises bioethical and legal considerations, and also has important implications for reproductive rights and the abortion debate. [36]

Artificial uteri may expand the range of fetal viability, raising questions about the role that fetal viability plays within abortion law. Within severance theory, for example, abortion rights only include the right to remove the fetus, and do not always extend to the termination of the fetus. If transferring the fetus from a woman's womb to an artificial uterus is possible, the choice to terminate a pregnancy in this way could provide an alternative to aborting the fetus. [37] [38]

A 2007 essay theorizes that children who develop in an artificial uterus may lack "some essential bond with their mothers that other children have". [39]

Gender equality

In the 1970 book The Dialectic of Sex , feminist Shulamith Firestone wrote that differences in biological reproductive roles are a source of gender inequality. Firestone singled out pregnancy and childbirth, making the argument that an artificial womb would free "women from the tyranny of their reproductive biology." [40] [41]

Arathi Prasad argues in her column on The Guardian in her article "How artificial wombs will change our ideas of gender, family and equality" that "[i]t will ... give men an essential tool to have a child entirely without a woman, should they choose. It will ask us to question concepts of gender and parenthood." She furthermore argues for the benefits for same-sex couples, saying: "It might also mean that the divide between mother and father can be dispensed with: a womb outside a woman’s body would serve women, trans women and male same-sex couples equally without prejudice." [42]

See also

Related Research Articles

<span class="mw-page-title-main">Pregnancy (mammals)</span> Period of reproduction

In mammals, pregnancy is the period of reproduction during which a female carries one or more live offspring from implantation in the uterus through gestation. It begins when a fertilized zygote implants in the female's uterus, and ends once it leaves the uterus.

<span class="mw-page-title-main">Placenta</span> Organ that connects the fetus to the uterine wall

The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate maternal and fetal circulations, and is an important endocrine organ, producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth. Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.

<span class="mw-page-title-main">Amniocentesis</span> Sampling of amniotic fluid done mainly to detect fetal chromosomal abnormalities

Amniocentesis is a medical procedure used primarily in the prenatal diagnosis of genetic conditions. It has other uses such as in the assessment of infection and fetal lung maturity. Prenatal diagnostic testing, which includes amniocentesis, is necessary to conclusively diagnose the majority of genetic disorders, with amniocentesis being the gold-standard procedure after 15 weeks' gestation.

The amniotic sac, also called the bag of waters or the membranes, is the sac in which the embryo and later fetus develops in amniotes. It is a thin but tough transparent pair of membranes that hold a developing embryo until shortly before birth. The inner of these membranes, the amnion, encloses the amniotic cavity, containing the amniotic fluid and the embryo. The outer membrane, the chorion, contains the amnion and is part of the placenta. On the outer side, the amniotic sac is connected to the yolk sac, the allantois, and via the umbilical cord, the placenta.

<span class="mw-page-title-main">Amnion</span> Innermost membranous sac that surrounds and protects a developing embryo

The amnion is a membrane that closely covers human and various other embryos when they first form. It fills with amniotic fluid, which causes the amnion to expand and become the amniotic sac that provides a protective environment for the developing embryo. The amnion, along with the chorion, the yolk sac and the allantois protect the embryo. In birds, reptiles and monotremes, the protective sac is enclosed in a shell. In marsupials and placental mammals, it is enclosed in a uterus.

<span class="mw-page-title-main">Obstetric ultrasonography</span> Use of medical ultrasonography in pregnancy

Obstetric ultrasonography, or prenatal ultrasound, is the use of medical ultrasonography in pregnancy, in which sound waves are used to create real-time visual images of the developing embryo or fetus in the uterus (womb). The procedure is a standard part of prenatal care in many countries, as it can provide a variety of information about the health of the mother, the timing and progress of the pregnancy, and the health and development of the embryo or fetus.

Fetal distress, also known as non-reassuring fetal status, is a condition during pregnancy or labor in which the fetus shows signs of inadequate oxygenation. Due to its imprecision, the term "fetal distress" has fallen out of use in American obstetrics. The term "non-reassuring fetal status" has largely replaced it. It is characterized by changes in fetal movement, growth, heart rate, and presence of meconium stained fluid.

Oligohydramnios is a medical condition in pregnancy characterized by a deficiency of amniotic fluid, the fluid that surrounds the fetus in the abdomen, in the amniotic sac. The limiting case is anhydramnios, where there is a complete absence of amniotic fluid. It is typically diagnosed by ultrasound when the amniotic fluid index (AFI) measures less than 5 cm or when the single deepest pocket (SDP) of amniotic fluid measures less than 2 cm. Amniotic fluid is necessary to allow for normal fetal movement, lung development, and cushioning from uterine compression. Low amniotic fluid can be attributed to a maternal, fetal, placental or idiopathic cause and can result in poor fetal outcomes including death. The prognosis of the fetus is dependent on the etiology, gestational age at diagnosis, and the severity of the oligohydramnios.

Rupture of membranes (ROM) or amniorrhexis is a term used during pregnancy to describe a rupture of the amniotic sac. Normally, it occurs spontaneously at full term either during or at the beginning of labor. Rupture of the membranes is known colloquially as "breaking (one's) water," especially when induced rather than spontaneous, or as one's "water breaking". A premature rupture of membranes (PROM) is a rupture of the amnion that occurs at full term and prior to the onset of labor. In cases of PROM, options include expectant management without intervention, or interventions such as oxytocin or other methods of labor induction, and both are usually accompanied by close monitoring of maternal and fetal health. Preterm premature rupture of membranes (PPROM) is when water breaks both before the onset of labor and before the pregnancy's 37 week gestation. In the United States, more than 120,000 pregnancies per year are affected by a premature rupture of membranes, which is the cause of about one third of preterm deliveries.

Ectogenesis is the growth of an organism in an artificial environment, outside the body in which it would normally be found, such as the growth of an embryo or fetus outside the mother's body, or the growth of bacteria outside the body of a host. The term was coined by British scientist J. B. S. Haldane in 1924.

<span class="mw-page-title-main">Placental abruption</span> Medical condition

Placental abruption is when the placenta separates early from the uterus, in other words separates before childbirth. It occurs most commonly around 25 weeks of pregnancy. Symptoms may include vaginal bleeding, lower abdominal pain, and dangerously low blood pressure. Complications for the mother can include disseminated intravascular coagulopathy and kidney failure. Complications for the baby can include fetal distress, low birthweight, preterm delivery, and stillbirth.

<span class="mw-page-title-main">Prelabor rupture of membranes</span> Breakage of the amniotic sac before the onset of labour

Prelabor rupture of membranes (PROM), previously known as premature rupture of membranes, is breakage of the amniotic sac before the onset of labour. Women usually experience a painless gush or a steady leakage of fluid from the vagina. Complications in the baby may include premature birth, cord compression, and infection. Complications in the mother may include placental abruption and postpartum endometritis.

<i>Fetal surgery</i> Growing branch of maternal-fetal medicine

Fetal surgery, also known as antenatal surgery or prenatal surgery, is a growing branch of maternal-fetal medicine that covers any of a broad range of surgical techniques that are used to treat congenital abnormalities in fetuses who are still in the pregnant uterus. There are three main types: open fetal surgery, which involves completely opening the uterus to operate on the fetus; minimally invasive fetoscopic surgery, which uses small incisions and is guided by fetoscopy and sonography; and percutaneous fetal therapy, which involves placing a catheter under continuous ultrasound guidance.

<span class="mw-page-title-main">Velamentous cord insertion</span> Velamentous placenta

Velamentous cord insertion is a complication of pregnancy where the umbilical cord is inserted in the fetal membranes. It is a major cause of antepartum hemorrhage that leads to loss of fetal blood and associated with high perinatal mortality. In normal pregnancies, the umbilical cord inserts into the middle of the placental mass and is completely encased by the amniotic sac. The vessels are hence normally protected by Wharton's jelly, which prevents rupture during pregnancy and labor. In velamentous cord insertion, the vessels of the umbilical cord are improperly inserted in the chorioamniotic membrane, and hence the vessels traverse between the amnion and the chorion towards the placenta. Without Wharton's jelly protecting the vessels, the exposed vessels are susceptible to compression and rupture.

A fetus or foetus is the unborn mammalian offspring that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a continuum, with no clear defining feature distinguishing an embryo from a fetus. However, in general a fetus is characterized by the presence of all the major body organs, though they will not yet be fully developed and functional, and some may not yet be situated in their final anatomical location.

An obstetric labor complication is a difficulty or abnormality that arises during the process of labor or delivery.

The following outline is provided as an overview of and topical guide to obstetrics:

<span class="mw-page-title-main">Fetal membranes</span> Amnion and chorion which surround and protect a developing fetus

The fetal membranes are the four extraembryonic membranes, associated with the developing embryo, and fetus in humans and other mammals. They are the amnion, chorion, allantois, and yolk sac. The amnion and the chorion are the chorioamniotic membranes that make up the amniotic sac which surrounds and protects the embryo. The fetal membranes are four of six accessory organs developed by the conceptus that are not part of the embryo itself, the other two are the placenta, and the umbilical cord.

<span class="mw-page-title-main">Circumvallate placenta</span> Medical condition

Circumvallate placenta is a rare condition affecting about 1-2% of pregnancies, in which the amnion and chorion fetal membranes essentially "double back" on the fetal side around the edges of the placenta. After delivery, a circumvallate placenta has a thick ring of membranes on its fetal surface. Circumvallate placenta is a placental morphological abnormality associated with increased fetal morbidity and mortality due to the restricted availability of nutrients and oxygen to the developing fetus.

Amnioinfusion is a method in which isotonic fluid is instilled into the uterine cavity.

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  37. ↑ Randall, Vernellia; Randall, Tshaka C. (22 March 2008). "Built in Obsolescence: The Coming End to the Abortion Debate". SSRN. doi:10.2139/ssrn.1112367. S2CID   57105464.
  38. ↑ Chessen, Matt. "Artificial Wombs Could Outlaw Abortion". Mattlesnake.com. Archived from the original on 12 October 2019. Retrieved 2 November 2014.
  39. ↑ Smajdor, Anna (Summer 2007). "The Moral Imperative for Ectogenesis" (PDF). Cambridge Quarterly of Healthcare Ethics. 16 (3): 336–45. doi:10.1017/s0963180107070405 (inactive 1 November 2024). PMID   17695628. S2CID   36754378. Archived from the original (PDF) on 11 September 2013.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
  40. ↑ Chemaly, Soraya (23 February 2012). "What Do Artificial Wombs Mean for Women?". RH Reality Check.
  41. ↑ Rosen, Christine (2003). "Why Not Artificial Wombs?" (PDF). The New Atlantis. Archived from the original (PDF) on 1 August 2014.
  42. ↑ "How artificial wombs will change our ideas of gender, family and equality". The Guardian. 1 May 2017. ISSN   0261-3077 . Retrieved 16 June 2017.

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