The University of Southampton

Author: Shannon Yu

Are artificial embryos the future for fertility?

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45 years ago, Louise Brown shocked the world as the first ‘test-tube baby’. Whilst in vitro fertilisation (IVF) was initially met with a knee-jerk revulsion, Louise’s birth has since been a turning point in the treatment of infertility. Could a child developed from artificial gametes undergo this same path?

IVG vs IVF process. Produced in Biorender.

As an aspiring clinical embryologist, I champion assisted reproductive technologies (ART) such as IVF. However, when I came across the idea of assisted reproduction using artificial gametes, termed ‘in vitro gametogenesis (IVG)’, my reaction was immediately apprehensive.

In the same manner as how IVF practice was initially received as scientists ‘playing god’, my thoughts concerned whether IVG fits into the natural order. Although artificial gametes produce artificial embryos, would full prenatal development of these cells lead to artificial life? This question brought my mind to Kazuo Ishiguro’s science fiction novel ‘Never Let Me Go’ which delves into the meaning of humanity through the lens of human cloning as a means of organ donation. Despite their unconventional origins of conception and development, I was moved to read the injustices imposed on the clones who processed our same fully human thoughts and feelings. Whilst I don’t find the novel’s cloning institutions morally or ethically appropriate, this warmed me to IVG technology and the belief that children potentially born from artificial gametes would still hold valuable and meaningful lives.

Ishiguro’s ‘Never Let Me Go’. The main character highlights the revulsion felt by the society toward clones like herself.

What IVG could have to offer

The more I researched the applications of IVG within the broader context of society, the more my support for this putative technology grew.

IVG obtains gametes via reprogramming somatic cells into pluripotent stem cells. Therefore, it offers infertile couples, and even same-sex couples, the ability to generate viable gametes and have genetically related offspring.

If made readily accessible, IVG may offer an alternative to the standard hormonal stimulation for egg retrieval, alleviating women from the physical and emotional demands of the procedure.

Due to DNA-damaging chemotherapy and radiation treatment, IVG would be especially useful amongst cancer patients who may not have the time to conduct cryopreservation at the risk of delaying urgent anti-cancer treatment.

IVG would also provide an unlimited production of embryos, opening more avenues for developmental research.

Ethical considerations

While IVG has demonstrated success in mice, significant research and resolution of ethical and legislative challenges are required before its applications become a clinical reality for humans.

The prospect of generating embryos from any somatic cell raises concerns regarding unauthorised gamete creation. For instance, it may enable celebrity DNA theft. Although legislation could mandate cell samples to only be obtained in clinical settings with formal consent, the system could be easily exploited.

Theoretically, ‘uni-babies’ may be possible, where a set of gametes are reprogrammed from a single individual.

It brings to question the impacts on adoption.

Combined with gene-editing tools like CRISPR, the unlimited supply of IVG embryos could potentiate embryo farming and accelerate the concept of ‘designer babies’.

With UK legislation ruling a 14-day cut-off for human embryonic research, it may be questioned whether this period should be extended for artificial embryos. However, particularly if IVG is used as ART, artificial embryos should be applied under the same legislation as natural ones.

A biotech startup, Conception, claims they are ‘quite close to being able to have proof-of-concept human eggs’ derived from blood cells. Although the successful application of IVG in humans is years away, I think it would be a revolutionary technology that positively eliminates reproductive barriers for future generations.

A regenerative approach to reverse menopause?

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As an aspiring Clinical Embryologist, I was particularly interested in our lecture on tissue engineering and promoting tissue regeneration. In the reproductive system, ovaries are generally the first to suffer decline in function over time. With a growing number of modern women seeking to beat age-related declines in fertility levels, there is much potential in using regenerative medicine strategies to restore ovarian function and overcome infertility. In 2016, success in a new experimental technique to increase fertility potential was published, using platelet-rich plasma (PRP), termed ovarian rejuvenation.

How does ovarian rejuvenation work?

PRP treatment has been used to treat osteoarthritis and joint degeneration. It involves separation of a patient’s blood sample via a centrifugation process to remove red and white blood cells to obtain a concentrated sample of plasma with a 5 to 10 fold higher concentration of platelets. Platelets are well known for their blood clotting abilities; however, they also facilitate tissue regeneration. Platelets contain granules which deliver various growth factors upon activation, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF). These promote vessel wall permeability and proliferation of endothelial cells and fibroblasts. Since 2016, interest has grown for applications of PRP in reproductive biology, where direct injection of PRP into the ovary has been reported to induce hormone stabilisation and resumption of menstrual cycles in infertile menopausal women.

Figure 1. Process of ovarian rejuvenation (https://www.ivf-spain.com/en/regenerative-fertility-medicine/)

UK regulations

Whilst ovarian PRP treatment is actively in practice in countries such as Greece, USA and Turkey, it is not currently approved for in the UK by the Human Fertilisation and Embryology Authority (HFEA). Additional therapies and techniques such as ovarian rejuvenation are classified by the HFEA as fertility treatment ‘add-ons’. Although add-ons aim to improve fertility treatment outcomes, the evidence to support their efficacy and outcomes is usually missing, limited or lack reliability. With the UK fertility sector being a competitive market and where 60% of treatments are privately funded by patients, the HFEA is concerned that add-ons are offered for commercial interests rather than as best practice for patients. In December 2023, the Progress Educational Trust held a conference on ‘Updating Fertility, Embryo and Surrogacy Law’ where the HFEA proposed implicating fines as sanctions to fertility clinics for mis-selling of add-ons. Case studies of ovarian rejuvenation appear to present encouraging outcomes, however, there are often limitations in their experimental design such as by absence of sham injection groups or randomisation. The duration of effect after ovarian PRP is unknown, and potential short- and long-term risks are not yet understood. A large-scale, controlled randomised clinical trial is required to confirm efficacy of the therapy before ovarian rejuvenation may be introduced into UK clinics.

Ethical considerations

Ovarian rejuvenation has potential to improve chances of older and menopausal women conceiving their own biological child. However, some debate whether it is ethically acceptable to become a mother at an advanced age, given the likelihood of medical and health-related risks for both the mother and offspring.

I believe that such views are culturally skewed by ageism and ableism, leading to portrayal of older mothers as deliberately risk-taking when infertility and age of motherhood arises from life circumstances outside of a woman’s control. I hope that sufficient research may soon be conducted to prove efficacy of ovarian rejuvenation and its related regenerative therapies in fertility.

References

Pantos K. et al. Ovarian rejuvenation and folliculogenesis reactivation in peri-menopausal women after autologous platelet-rich plasma treatment: https://sa1s3.patientpop.com/assets/docs/111052.pdf

HFEA, The responsible use of treatment add-ons in fertility services: a consensus statement: https://www.hfea.gov.uk/media/kublgcp3/2023-10-19-treatment-add-ons-consensus-statement.pdf

Louisa Gheveart Associates, Fertility Law Reform In The UK: How Much Change Do We Want?: https://louisaghevaertassociates.co.uk/fertility-law-reform-in-the-uk-how-much-change-change-do-we-want/

CelluBridge: A bridge to plant based body parts?

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As a Biomedical Scientist student, I am particularly interested in the use of stem cells and embryonic stem cells in developing organs that are able to cure disease. Whilst most research has stemmed from using human and animal cells, it wasn’t until I came across this news story that opened my mind up to the possibility of growing organs and body parts from just an apple or asparagus.

A video on stem cells