Singapore

Public consultation needed on Singapore’s reproductive technologies

It will enable a holistic ‘big-picture’ view of relevant ethical, legal, and social issues

A staff member shows a mock-up of work being done on women's eggs in the laboratory at the KL Fertility Centre in Kuala Lumpur. (Photo: AFP / UCAN files)

By Dr. Alexis Heng

Published: November 13, 2023 11:47 AM GMT

Updated: November 14, 2023 04:16 AM GMT

In recent years, Singapore has increasingly leveraged new reproductive technologies to overcome the country's rapidly aging demographics and dismal fertility rate, which hit a new low in 2022.

Hence, it would be timely for Singapore’s Bioethics Advisory Committee (BAC) to critically examine relevant ethical, legal and social issues associated with newly emerging reproductive technology platforms, which are thus summarized as follows;

In Vitro Gametogenesis (IVG) refers to the generation of artificial lab-grown sperm and eggs from other cell types within the body such as skin cells. Utilizing advanced molecular biology techniques, skin cells can be reprogrammed into an embryonic stem cell-like state, which can then be induced into functional sperm or eggs by various chemicals and growth factors within a laboratory dish.

Several research groups in Japan and China have already demonstrated the birth of live healthy offspring from IVG-generated sperm and eggs derived from the skin cells of mice and rats, which could in turn reproduce normally and give rise to the next generation of healthy offspring. It is highly plausible that these will soon be replicated in humans within the near future.

Artificial Womb Technology (AWT) refers to bioengineered systems for the gestation of human offspring outside the human body, technically referred to as Ectogenesis or Ectogestation. To date, studies with animal models, particularly sheep, have developed artificial womb systems that are capable of sustaining the life and development of preterm fetuses.

It is anticipated that clinical trials of AWT to save lives and nurture the development of extremely premature human babies will commence very soon. Nevertheless, complete ectogenesis to sustain the development of human embryos over the entire gestation period will likely not be feasible in the near future.

Synthetic Human Embryos refer to embryo-like structures generated entirely from stem cells, thereby bypassing the natural process of fertilization without the need for either sperm or eggs. An Israeli research team at the Weizmann Institute of Science achieved this feat with mouse and human stem cells in quick succession, in 2022 and 2023 respectively.

These synthetic embryos were reported to display brains, beating hearts, as well as foundational structures of all other organs within the body, in addition to also possessing rudimentary placenta, yolk sac, and other external tissues that could potentially ensure their continued growth and development upon transfer into a womb.

To date, no animal or human-derived synthetic embryos have yet generated a live offspring, but given the rapid pace of scientific advancements in recent years, this hurdle may likely be overcome soon.

Overlying these three key reproductive technology platforms are artificial intelligence (AI)-based embryo polygenic screening and human germline genome editing, which can not only prevent and cure genetic diseases but can also be utilized for human enhancement. This refers to the screening, selection or genetic engineering of non-disease socially desirable traits in human offspring, such as higher IQ, tallness, and fair complexion; which has at least been partially or wholly discussed in previous BAC-led public consultations.

A future public consultation on newly emerging reproductive technologies initiated by Singapore's BAC should therefore address the following pertinent issues:

Treatment of age-related female infertility, as adjunct and complementary to conventional fertility preservation procedures such as egg freezing and ovarian tissue freezing. This might give rise to new ethical issues such as pressure on women to give birth at an advanced age or pressure on women to follow “male” career structures.
Posthumous reproduction for bereaved spouses and parents. Tissues and cells could be harvested from a corpse, upon the untimely death of a loved one, and be used to produce synthetic embryos, or artificial eggs and sperm via IVG, with gestation in an artificial womb. Needless to say, this would be highly controversial, especially if there is no informed consent from the deceased. Additionally, there are also ethical concerns about the rights, welfare, and psychological impact on posthumous children.
Utilization of such technologies by de facto same-sex couples (gay and lesbian marriages are banned in Singapore), to beget offspring that are genetically related to both partners in such unconventional relationships. Even if the utilization of such new reproductive technologies is banned for de facto same-sex couples in Singapore, these can still be done overseas. The resulting offspring will thus pose a quagmire for the Singapore Government, which has to resolve legal issues pertaining to residency, citizenship, and parenthood rights.
IVG technology can facilitate the mass production of donor sperm and eggs for infertile patients, which are currently in short supply worldwide. Customized IVG for individual patients would likely lead to excess production of eggs and sperm which may be donated to other infertile patients who cannot afford the high costs of the procedure. There are increased risks of unintended incestuous sexual relationships and marriages between numerous donor-conceived offspring of a single individual, which may be further exacerbated by the high population density and small size of Singapore. Even more contentious would be the mass production of donor eggs and sperm from highly desirable and accomplished individuals such as famous actors and actresses, fashion models, sports stars, brilliant scientists, and acclaimed musicians, to supply boutique eugenics agencies.
A key technical bottleneck in AI-based embryo polygenic screening and human germline genome editing is the limited number of embryos available for screening, selection, or gene modification. This may be overcome through IVG technology or the generation of synthetic human embryos from stem cells. The key ethical issue here lies in the application of such technologies for human enhancement, that is the screening, selection, or genetic engineering of non-disease socially desirable traits such as high IQ, athletic prowess, and physical characteristics related to beauty standards.
The use (or abuse) of artificial womb technology to enable otherwise healthy and fertile women to avoid the physical burdens and pains of pregnancy and childbirth, so as to achieve a new form of gender equality and feminist liberation, as well as to obviate the need to take maternity leave so that they can focus on their work and career advancement.
To avoid or lessen the moral guilt of abortion by sustaining the life and development of aborted fetuses via artificial womb technology, and then giving the child up for adoption or orphanage upbringing.
If synthetic human embryos generated entirely from stem cells can be proven to be fully capable of generating a live offspring upon transfer into either a natural human womb or artificial womb, then questions will surely arise on their personhood and moral status and whether it is ethical to utilize them for various non-reproductive biomedical applications. For example, synthetic human embryos can serve as a source of transplantable tissues and organs, as well as a screening and testing platform for newly developed pharmaceutical drugs.

In conclusion, given the rapid progress that has been made in these aforementioned newly-emerging assisted reproductive technology platforms in recent years, it is imperative to initiate a multi-disciplinary discussion of the relevant ethical, legal, and social issues among policymakers, medical professionals, biomedical scientists, religious leaders and various members of the general public.

Dr. Alexis Heng is an associate professor of biomedical science at Peking University, China. He is ranked among the top 2 percent of scientists worldwide in 2022 by Stanford University. To date, he has published 50 international journal articles on legal, ethical, and sociological issues relating to new reproductive technologies, besides having around 300 scientific journal publications.

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