Ectogenesis: understanding opportunities, implications, concerns, and ways forward

Ectogenesis is the practice of developing organisms in artificial settings, with applications that range from improving the outcomes of preterm babies to treating fertility issues. It was unveiled in 2017 and provides possibilities for both partial and full ectogenesis while sustaining fetal lambs with concepts like the biobag. Utilizing biobag artificial uteri, complete ectogenesis is the confinement of a woman’s pregnancy in an artificial womb from the inception of the embryonic stage to full gestation; while partial ectogenesis is the utilization of a biobag artificial uterus to continue gestation ex-utero. Ectogenesis may have advantages, but there are concerns about how it will affect children’s social and psychological development. It can benefit biological parenthood, newborn care, fetal therapy, maternal-fetal disputes, societal growth, reduce health risks, and alter cultural norms while promoting reproductive equity. Due to possible risks, rigorous research on human subjects is required before ectogenesis may be implemented. The paper seeks to provide a thorough study for society’s conversation and deliberation, examining its potential advantages as well as its technical, ethical, and regulatory elements.


Introduction
Infertility and stillbirth are global health issues that lead to diseases such as stroke [1] .While infertility is experienced by around 48 million couples and 186 million individuals worldwide [2] , there is a wide range in stillbirth rates, with the highest rates being reported in low-income Sub-Saharan Africa and Southeast Asian countries.These rates, which range from 20 to 40 per 1000 births, are over 10 times greater than those reported in highresource environments.In low-income and middle-income countries, mostly in areas with limited resources, stillbirths account for about 98% of all births [3] .To tackle those issues, the world has already seen some form of it in medical practice today, sometimes called 'artificial womb', also called 'Ectogenesis'.Ectogenesis is the process of functional evolution of a fetus in an artificial environment outside the natural womb, such as growing a fetus outside a woman's body.This new health technology provides hope of having a baby, who otherwise will never have due to biological limitations [4,5] .This may also address stillbirths which at present is ~2.7 million third-trimester stillbirths globally, the majority of which may be avoided while improving the survival rate of premature babies [3] .Ectogenesis has been postulated to reduce the mortality and morbidity ratio by providing ectogestation to extremely premature babies with the prevailing crucial care.This allows a preterm baby on the verge of complications and subsequent death to be placed in an artificial womb to allow for enough development and maturity to considerably boost its health outcomes [5] .
Following the disastrous quakes that hit Turkey and Syria on 6 February 2023, pregnant women in the affected areas might encounter uncommon challenges in getting access to quality healthcare.Expectant mothers might have been left without access to crucial prenatal care and medical services due to the already weakened healthcare infrastructure and ongoing instability [6] .The creation of artificial wombs appears to be a potentially transformative option in such conflict-ridden disaster zones.Artificial wombs could reduce the hazards of birthing in unhygienic settings and provide a lifeline for expectant women willing to access proper medical facilities by offering a controlled and safe environment during gestation.This creative strategy, along with the rehabilitation of the healthcare system and psychological assistance, might greatly reduce the enormous responsibilities carried by expectant mothers [7] .Understanding this concept of ectogenesis will advance modern medical practices by enhancing scientific understanding of embryonic development and its applications in regenerative medicine [8] .This study can help address ethical concerns about how human life begins and reproductive options while promoting reproductive equality through alternatives to traditional pregnancy [9] .This paper discusses ectogenesis, or the artificial womb, and provides an analysis to contribute to global discussion and debate.

The process of ectogenesis
Ectogenesis is partial when part of the pregnancy period takes place outside the maternal body.Partial ectogenesis occurs when preterm infants are placed in an incubator to continue their growth and development in a neonatal setting [10] .The utilization of a biobag artificial womb to continue gestation ex-utero is also termed partial ectogenesis [11] .A woman's pregnancy is considered complete ectogenesis when it is fully within the confinement of a man-made womb from the start of the embryonic stage to delivery [12] .To fulfill the goal of pregnancy, an ectogenesis device requires an envelope that houses the fetus, amniotic fluid that encloses the embryo, and a regulatory system of the umbilical cord that delivers the appropriate quantity of oxygen, hormones, and nutrients.The uterus houses the fetus inside the mother to facilitate growth and development during natural gestation, which corresponds to an artificial envelope in the process of ectogenesis [13,14] .
Biobag was developed as a completely impenetrable, onetime-use system customized to balance amniotic fluid levels to imitate the shape and size of the womb.This artificial womb is built of transparent, sound-porous, and elastic polyethylene film to permit fetal supervision, manipulation, and scanning as required.A free adjustable side is incorporated to allow the insertion of the embryo during cannulation.Several watertight connectors are formulated to enhance cannulas, probes, temperature, and pure suction pipe.This artificial womb, after cannulation, is locked and placed in a movable support system that comprises circuitry for fluid exchange and reservoir, padding, temperature regulation, and pressure.The artificial womb is an incorporation of the locked fluid, no pump oxygenator circuit, and cannulae acting as umbilical cord.These are designed to imitate the natural womb environment with the capacity of sustaining premature lamb fetuses for 28 days [11] .There has been a proven record of normal lung and circulation growth with no infection among the tested subjects of the biobag artificial womb [15] .

Implications of ectogenesis
The full implementation of ectogenesis for human use might lead to the use of ecto-babies as a subject of lengthy research, discussions, and media awareness on public platforms.This poses severe social damage to the baby just because having been born from a man-made womb [16] .Children born through this artificial womb might face challenges of privacy invasion and loss as well as psychological harm to some children's well-being as a result of intensive studies on them [17] .Attention has been paid, and more will definitely be paid, to the psychological impact of ectogenesis on the ecto-children with the belief that they lack the sensory experience and emotional development of a natural pregnancy because of the detachment from their mothers [18] .
Ectogenesis will produce children with emotional, biological, and physical distance from their mothers when growing in an artificial medium.This is because pregnant women during natural gestation generate relational and friendly psychology, talking and singing to their yet-delivered baby when being twisted or kicked, as well as labor from emotional and physical feelings [12] .Ectogenesis has been designed to provide ectogestation to premature infants to increase their chances of surviving while preventing the mothers from losing their children, which could lead to a psychological and mental burden on the mother in the long run.The accessibility of ectogestation will allow some women planning to eliminate their pregnancy willingly to follow their desires of reproductive liberty and enjoy their life without having to end the life of the embryo, supporting the will of the fetus, while providing a long-lasting solution to the maternal-fetal conflict and subsequently reducing the rate of abortion by offering hope to many children [19] .
Ectogenesis allows couples with fertility problems to conceive and become the true biological parents of their child, minimizing the child's and the mother's mortality rates as a result of pregnancy complications, easing women's suffering, and reducing the chances of cesarean sections.Women who have experienced hysterectomy with preserved ovaries will have an alternative way of giving birth to their true child via ectogenesis.Countries experiencing drastic population declines can implement ectogenesis to boost their populations [20] .This approach also helps reduce the suffering related to miscarriages, uterine transplantation, and its related complications.Another beneficial advantage is the provision of an alternative option to surrogacy, a type of assisted reproductive technology [21] .An unplanned pregnancy can also be placed in an artificial womb instead of being terminated [22] .

Concerns and way forward
Pregnancy is an integral part of women's lives, and the inability to pass through the phase of pregnancy can impact their personalities as women.The uterus represents a sign of womanhood, which is one of the biological differences between men and women.The natural relationship between the mother and the child is one of many significant sources of authority for mothers in some communities in Africa and Asia [21] .The ease of access to the artificial womb is a growing concern, limiting better opportunities for transgender individuals, same-sex couples, and single men to become the true biological parents of their children.Some single men may be compelled by this idea of pregnancy outside the woman's body, leading to the devaluation of women in some communities to start single men's families [12,21] .
Finding suitable in-vitro settings and the right technology to control crucial factors like perfusion pressure and oxygen provide ongoing and significant challenges.However, at this time, ectogenesis is not being enabled by research being done on the creation of tissue engineered uteri [12] .There are possibilities that extremely premature babies of less than 26 weeks might have some inevitable complications and risks [23] .The implementation of artificial womb technology will require experimental research on human subjects, which might expose both the mother and the baby to unidentified risks [11] .In partial ectogenesis, the pregnant mother will have to undergo an incision just like that of a cesarean to the womb during the early stage of the pregnancy, which would leave a comparative deeper scar behind with an increased future womb rupture and abnormal implantation of the placenta [24,25] .This approach poses a highly significant risk for both the mother and the fetus compared to a cesarean [22,26] .
Artificial womb technology can be explored further to improve the current standards of newborn care and reduce the mortality and morbidity rate among extremely premature babies who cannot live with the present newborn intensive care [27] .Application of full ectogenesis in real life could pave the way for fetal therapy and surgical procedures in an extrauterine womb, minimizing the risks of womb rupture, and complications for the pregnant mother [28] .This technology could be recommended for fetal genome medicine for both disease and nondisease associated traits [12] .
People with damaged or lost wombs due to cancer, disease, or congenital anomalies can also become the true biological parents of their child [28] .A hazardous but needed pregnancy that endangers the mother's life can have hope of continued pregnancy outside the uterine womb with the expectation of saving both the mother's and the infant's life [11] .Reproduction and social inequalities could be liberated.This will balance the equality between husband and wife, addressing all physical, financial, and social burdens related to childbearing to increase equality between sexes [29] .Women could be free from the potential burdens, risks, and constraints of pregnancy, labor, and childbirth [30,31] .Ectogenesis raises a number of ethical questions, such as the uncertainty surrounding fetal health and development, moral challenges in research and experimentation, the need for new legal frameworks, potential cultural shifts in norms, potential access disparities deepening social inequalities, disruptions to societal norms, debates over altering with nature, risks of exploitation for commercial gain, and genetic engineering [4,12] .
The creation of artificial wombs, allowing fetuses or embryos to grow outside of the human body, has many difficulties.Technical challenges include regulating immunological interactions, creating a proper embryo-fetal interface, and duplicating the complex biological setting of the womb.The beginning of life, personality, and societal changes raise ethical questions.Legal and regulatory frameworks, accessibility, and public acceptance, in addition to ensuring the long-term health and development of artificially gestated fetuses, provide additional concerns [32] .

Future directions and recommendations for global context
The future direction of ectogenesis in clinical settings, requires safety, technical, and ethical issues to be resolved.These difficulties involve womb complexity simulation and interface design for optimal fetal development, issues like umbilical vascular spasticity, restricted placental functioning, hormone and nutrition administration, monitoring organ development, and catheter insertion [12,33] .Differences between animal and human models raise ethical questions, which prompt cautious forecasts of clinical results.Approaches include employing more human-like animal models and using human subjects, including embryos and fetuses, which raises issues with consent and ethics [33,34] .Important considerations, including substantial research, stringent monitoring, and continuing informed consent, are expedient in order to strike a balance between risk and reward [35] .A contentious standard that necessitates thorough analysis and society's involvement is necessary to ensure 'no or very little harm' to future generations.To guarantee the safety, efficacy, and moral soundness of ectogenesis on the path to clinical applications, strict indications, long-term monitoring, and continual consent are crucial [12,33] .
Experts and stakeholders should work together to address technological, moral, and societal issues in order to advance this artificial womb technology.Priorities include the creation of clear ethical frameworks, ongoing technology innovation to replicate the womb's environment, and multidisciplinary research to close physiological gaps between humans and animals [9] .These recommendations support thorough preclinical research, processes for obtaining informed permission, and a methodical approach to clinical introduction.Long-term follow-up studies are necessary to evaluate people's well-being, and for responsible adoption, public awareness campaigns, and a global regulatory agreement are important.Additionally emphasized are ensuring fair access, advancing technology, maintaining research funding, and preserving privacy.The proper integration of ectogenesis into reproductive medicine depends on the ongoing discussion of revised thoughts in light of new understanding and ethical issues [32,34,35] .

Conclusion
Artificial womb technology is a novel scientific development in the field of medicine, especially in the intensive treatment and care of neonates.Ectogenesis is a new concept and new health technology that is yet to be fully explored.It is a new health technology with a seeming promise of solving problems related to all forms of infertility, stillbirths, and early birth and enabling women to conceive a baby at literally any age while avoiding any form of biological stress they might encounter through natural pregnancy.It poses intricate questions with multiple social, psychological, and ethical ramifications.Ectogenesis might alter parental styles, raising issues with privacy invasion, psychological injury, and the emotional estrangement of kids.It might also support reproductive equality, address medical hazards, and offer alternatives to surrogacy and abortion.Technical difficulties, ethical issues, consent issues, and regulatory frameworks are all possible difficulties.Collaboration, comprehensive research, public awareness, and ethical standards are needed to strike a balance between benefits and hazards.Although the technology has promise, careful thought and continual discussion are required.