Is Singapore ready for mass production of eggs and sperm from stem cells?

Scientists have generated artificial lab-grown sperm and eggs from rats and mice, which have gone on to successfully produced healthy offspring, a procedure known as In Vitro Gametogenesis (IVG). Progress has been rapid.

Back in 2016, researchers at the Institute of Zoology of the Chinese Academy of Sciences produced functional sperm from mouse stem cells that can generate healthy offspring, and these went on to give birth to the next generation.

In 2021, Katsuhiko Hayashi, of Kyushu University, generated functional eggs from skin-derived stem cells of mice. This was achieved by artificially replicating the natural soup of nutrients and growth factors present in mouse ovaries within the culture dish.

In April 2022, it was announced that Toshihiro Kobayashi, of Tokyo University, had derived functional sperm from rat stem cells that can generate viable offspring, a feat that was previously possible only with mice.

Are human applications ahead?

There are still many hurdles before IVG can be applied to humans. Nevertheless, it is highly plausible that the technique will eventually be realized for human fertility treatment.

How this works out in Singapore, a highly urbanized Asian country with ultra-low fertility rates, a rapidly aging population, and a sophisticated biotech industry will influence other East Asian countries.

IVG is complex, and labour-intensive, so it will cost much more than conventional fertility treatment — which is already extremely expensive. IVG for the relatively small number of patients with primary infertility arising from congenital defects, accidental injury to reproductive organs, chemotherapy and premature ovarian failure will not be commercially viable.

It is going to be a niche market for the wealthy. .

One application which could be exploited commercially is posthumous reproduction for bereaved spouses and parents. Tissues and cells could be harvested from a corpse and be used to produce artificial eggs and sperm via IVG, with the resulting embryos being transferred to a surrogate mother. Needless to say, this would be highly controversial, especially if there is no informed consent from the deceased. Additionally there are also ethical concerns pertaining to the rights, welfare and psychological impact on posthumous children.

Another tiny market would be transgender and intersex couples. Under Singapore law, intersex and transsexual people are allowed to get married, provided they have undergone gender-reassignment surgery, which allows them to legally change their gender on their personal identification documents. Nevertheless, there are very few intersex and transgender people in Singapore.

Market potential

So where is the market potential? There are four areas: age-related female infertility; same-sex couples; mass-production of donor eggs and sperm for the treatment of infertile patients; and mass-production of human eggs for eugenics applications.

In Singapore, there would be hardly any moral objections to treating age-related infertility with IVG. Singapore is a rapidly ageing society with one of the world’s lowest birth rates. The government is unlikely to discourage novel methods of producing more children. However, IVG may lead to new ethical issues in the treatment of age-related female infertility, such as pressure on women to give birth at an advanced age or pressure on women to follow “male” career structures.

More problematic would be IVG to enable gay and lesbian couples to have children that share their genetic heritage. For example, artificial eggs could be produced from male stem cells, which can be fertilized by sperm from another man, and the resulting embryos implanted into a surrogate mother. Likewise, artificial sperm can be produced from female stem cells and be used to impregnate another woman.

Even in Singapore, this might be a step too far. But same-sex Singaporean couples could still access IVG overseas. This could put legal and political pressure on the government to recognise offspring as Singaporean citizens. Indeed, recent court cases have emphasized the importance of genetic affinity and blood ties between children and parents, as well as prioritizing the child’s welfare above public policy based on societal norms.

For example, in the court ruling of the IVF sperm mix-up case by Thomson Fertility Centre a few years ago, it was explicitly stated that “The ordinary human experience is that parents and children are bound by ties of blood and this fact of biological experience — heredity — carries deep sociocultural significance.” In another landmark court case the Singapore High Court granted a gay man’s bid to adopt his biological son born via a surrogate mother. The Chief Justice declared that the need to promote the welfare of the child is paramount and outweighs public policy against the formation of same-sex family units.

My feeling is that the Singaporean government will reluctantly recognize the relationship of IVG-conceived children to same-sex parents. They will have citizenship and residency rights, parenthood subsidies, and automatic right of inheritance of the child to the parent’s estate, in the absence of a will.

Mass production of sperm and eggs for infertile patients could be a lucrative market but an ethical minefield. Customised IVG for individual patients would lead to excess production of eggs and sperm which could be donated to other infertile patients who cannot afford the high costs of the procedure.

Besides the obvious issue of informed consent of patients in the donation process, there are also ethical and legal issues related to the rights and welfare of children conceived in this manner. The most pressing of these involves the fractured and confused identity of donor-conceived children, and their right to know their genetic heritage, such as family history of hereditary diseases. It is for this reason that anonymous sperm and egg donation is currently banned in several Western countries.

Still more contentious would be mass production of eggs and sperm from film stars, fashion models, sport stars, brilliant musicians, Nobel prize-winning scientists and so on. If demand for eggs from a model or sperm from a baseball star were high enough, IVG could power up mass production to supply boutique eugenics agencies.  

Of course this risks unintended incestuous sexual relationships and marriages between numerous donor-conceived offspring of a single individual. There is also the possibility of the well-documented phenomenon of Genetic Sexual Attraction between close relatives who first meet as adults.

Finally, IVG has eugenic potential. Its promoters claim that it can be used to prevent transmission of genetic diseases. But the same techniques will facilitate eugenics for prospective parents. Even if genome editing is banned, IVG greatly increases the available number of embryos from which to select the “ideal” future child via genetic testing and analysis. Currently, artificial intelligence algorithms are being developed for selecting the best and healthiest IVF embryos via genetic screening.

After all, some bioethicists have argued, parents desire the best for their children. They invoke the theory of “procreative beneficence”, which holds that parents have significant moral reason to select, of the possible children they could have, the child who is most likely to experience the greatest well-being – that is, the most advantaged child, the child with the best chance at having the best life.

All these possibilities are coming down the pike. Fast. Singapore needs to be prepared.

Dr Alexis Heng Boon Chin is an associate professor of Biomedical Science at Peking University, China. He had previously worked in the field of human clinical assisted reproduction research in Singapore, and has authored 50 international journal publications on ethical and legal issues relating to new reproductive technologies, in addition to also having published more than 250 scientific journal articles.

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