We’ve all heard it before: a woman is born with all the eggs she will ever have. It’s a fundamental truth of biology and has always defined the boundaries of reproduction. But what happens if this biological reality is no longer fact? What if we could take an ordinary skin cell and transform it into an egg? What if embryonic stem cells could be reprogrammed to create entirely new oocytes? Or what if we could even make an egg from a man’s skin cell, completely eliminating the need for a woman’s gametes altogether?

This might sound like science fiction belonging to a reality far removed from our own, but these are no longer merely hypotheticals. They are real and current developments in assisted reproductive technology, and much like the use of AI and robots to create human lives, they signal that the dystopian future of IVF is already upon us.

In vitro gametogenesis (IVG), the creation of gametes (egg cells and sperm cells) in a dish, is one of the most rapidly advancing fields of reproductive biology. With each new step forward, we are forced to confront serious ethical questions. The recent advancements in IVG once again blur the lines of what we can do and what we should do.

At the heart of this debate lies a difficult question: Are we entitled to a biological child by any means science can offer? And at what cost to the dignity of human life?

The science of IVG: Turning skin cells in egg cells

IVG is a method to recapitulate the process of gamete growth and development outside the body. Naturally, the precursors to gametes called primordial germ cells (PGCs) form during early fetal development. These PGCs populate the fetal ovary or testes at around 2-3 weeks of gestation. PGCs in males give rise to spermatogonial stem cells that can self-renew and differentiate, allowing for generation of new sperm throughout most of a man’s adult life.

However, PGCs in females give rise to oocytes that lose the ability to self-renew, thereby creating a finite pool of gametes. That is, at birth, a woman has all the oocytes she’s ever going to have. Most of these oocytes undergo the normal process of atresia, or degeneration, before they are ever able to fully grow and ovulate. Once the pool is gone, a woman will enter menopause, signaling the end of her reproductive lifespan.

As such, artificial generation of oocytes to extend the reproductive potential of women beyond the normal limits is an alluring potential, and a sought-after scientific and clinical target.

The goal of IVG is to reprogram stem cells into functional eggs and sperm. These stem cells may originate from embryos or be induced from other cell types, such as skin or blood cells. Embryonic stem cells possess the unique capability to differentiate into any cell type, but their use raises concern due to the destruction of embryos. Alternatively, stem cells derived from skin cells offer a promising solution by avoiding these ethical issues. Through targeted genetic reprogramming, a skin cell can be guided to develop into a more specialized human gamete.

The original IVG: Reprogramming embryonic cells back into oocytes

In 2016, scientists in Japan published the first study showing successful IVG performed entirely in a dish using a mouse model. They used mouse embryonic stem cells to generate oocyte precursor cells that would eventually become fully grown oocytes, which were then fertilized and transplanted back into a recipient female. Pups that appeared normal were born as a result. However, several of the implanted embryos died in utero and those that were born alive had on average a heavier placenta, suggesting likely developmental issues within these IVG-derived animals that may have significant repercussions for overall health.

While not all stem cells are embryonic in nature, those that are derived from 3–5-day old preimplantation embryos are most appealing for current work in IVG because of their “blank slate” ability to develop into any type of cell. While this work was carried out using all mouse-derived cells, human embryonic stem cells are still widely used in research studies. Using a skin cell’s genetic material or reprogramming it to act like an embryonic stem cell is a much more idealized goal. However, eliminating the need for embryonic stem cells in IVG still does not make the process morally neutral.

A new and troubling method of IVG: “Mitomeiosis” or disordered DNA?

Just last month, a new study was published in Nature Communications demonstrating success with a new twist on IVG. If we remember from high school biology, mitosis is how most cells in our body make exact copies of themselves to grow or repair tissue. Meiosis, on the other hand, is the special kind of cell division that makes sperm and egg cells, which each have only half the normal amount of DNA. This is important so that when they combine, the resulting embryo has a full set of chromosomes.

In this study, Gutierrez and their team claim to have created a completely new process they call “mitomeiosis.” In their experiment, the researchers took the nucleus (which contains the DNA) from human skin cells and inserted it into human egg cells that had their own nuclei removed. The natural machinery inside the egg then caused this DNA to go through meiosis. When they added sperm, the remaining chromosomes in the egg joined with the 23 chromosomes from the sperm, forming embryos. This is a key distinction from cloning, which generates an embryo with an exact DNA match to the cell it is derived from rather than allowing a combination of egg and sperm DNA.

Normally, meiosis in oocytes is very precise. It keeps one copy of each chromosome and discards the other. But in this experiment, because the egg was working with a skin cell’s DNA, the process was messy. Division of chromosomes occurred randomly and imprecisely. After fertilization, many experimental human embryos were missing key chromosomes. Only about 9% of the embryos developed to the blastocyst stage, the stage of embryonic development just before implantation, and all of them had an abnormal number of total chromosomes.

In an OregonLive article, the corresponding author on the study Dr. Shoukhrat Mitalipov (known for his human embryo-destructive research involving cloning, embryonic stem cells, and gene editing) states “Nature gave us two methods, and we just developed a third.” Not only does this science flirt with Dr. Frankenstein-esque ideologies, but it will also need extensive experimentation to work out how to control the appropriate chromosome retention in the developed oocytes. This has already required the generation and destruction of hundreds of experimental and control human embryos for explicitly research purposes. As the boundaries of how far these embryos can develop are pushed further, human life will continue to be denigrated to the level of disposable research material.

The U.S. government will not provide funding for studies that create human embryos for solely research purposes, a fact that must be preserved. However, private funding and a lack of laws prohibiting cloning or human embryo generation for research purposes in Oregon have allowed for this research to proceed.

Not only did this new development lead to significant destruction of life, but it also relied on healthy women to sell their oocytes for exclusive use in this study. Women were paid approximately $7,000 to undergo hormonal stimulation and egg retrieval specifically to provide research materials to generate human embryos. This process subjects women to a myriad of potential health risks associated with hyperstimulation and retrieval. While the authors claim informed consent was given, the article fails to say whether these women were informed that embryos would be created and destroyed for this study. What was once unthinkable is now reality – healthy women are selling healthy gametes to create artificial eggs and real human embryos destined for death, all in the name of research progress.

Other major ethical considerations for IVG: Lack of consent, “embryo farming,” and the elimination of women

In an article published last year in Stem Cell Reports, the views of those who would most benefit from the technology of IVG were assessed. These primarily included “those experiencing involuntary childlessness due to biological or social infertility,” further redefining the definition of infertility to a social condition. The authors mention that safety of the technique was a primary concern, but the frequency of issues discussed overwhelmingly concern equity, financial burden, and the desire for a child and far outpace discussions involving the risks to the children conceived via this method. Couples don’t want to use the technique until it’s “tested,” but it will indeed be tested, and the unconsenting research subjects will be the smallest and most vulnerable among us.

In an ironic twist, the use of this technology is touted as a means to eliminate the need for egg retrieval and freezing. No need for ovarian stimulation and retrieval, something the participants notably and unsurprisingly deemed as “horrible” and “excruciating.” While this is a fortunate byproduct, it still renders this technique too readily accessible to the potential ethical abuses, especially the creation of gametes without consent. As several ethicists have noted, if gametes can be created from any old reprogrammed skin cell, what would stop someone from obtaining cells from an unsuspecting partner? Or even an idolized movie or sports star, to create eggs or sperm and, ultimately, an embryo and child from that individual without them ever knowing?

Not only does the generation of eggs from iPSCs create dilemmas regarding consent, but it could also allow for creation of embryos from same-sex parents. The same research team in Japan has recently achieved the first live births following oocyte-generation from a male skin cell. While the technology is far from efficient, with just 1% of embryos making it all the way to live pup, the implications of this technique are startling. There could be a complete elimination of the need for women to create a new life. Embryos could be created from two men, opening the doors to “bipaternal reproduction.” Or, even more radically, from a single individual. However, women would still need to carry these embryos, thereby increasing the demand for surrogates. If the unthinkable mechanized womb enters mainstream, then there will be no need for women at all.

Additionally, the authors of the study claim that this is a breakthrough in eliminating a specific aneuploidy, or abnormal number of chromosomes, that causes Down Syndrome. This perpetuates the already persistent problem of genetic selection of embryos. Since IVG is not limited by the number of eggs a woman can have retrieved, IVG will allow for the large-scale production of embryos, or “embryo farming,” in order to select the best, most desirable genetics. This will assuredly lead to the perpetuation of eugenic practices of eliminating and disposing of embryonic life deemed not desirable enough to be given the chance to live fully.

How close are we to the reality of IVG in clinical use?

Some claim the technology to put IVG into clinical practice is 10-20 years away. Dr. Katsuhiko Hayashi of the team responsible for the original 2016 breakthrough study estimates his group is seven years away from creating viable, fully lab grown human eggs and sperm.

Private industry has also gotten into the IVG game. Conception, a biotech startup in Berkeley, CA, claims to have made headway by producing eggs, as well as the follicles made of cells that typically surround and support eggs within the ovary, all in vitro. However, private companies typically keep their scientific advancements as proprietary and don’t share or publish their methods and results, so there is no way to substantiate their claims yet.

IVG exploits a few key scientific processes used by nature to create eggs capable of fertilization, and what was once thought to be unreachable is now possible. However, early embryonic development involves the precise coordination of so many other genetic and epigenetic processes – developmental programming that ensures the proper health and development of the individual not just in utero, but throughout their entire life. There is still so much that is unknown about how these events occur in nature, let alone how to ensure they are carried out properly in a dish.

It is more likely that, for now, IVG will be used at the research level. It is touted as a method to better understand early human development, model infertility, explore new treatments, and improve artificial reproductive technologies. However, the goal of this research is also to put IVG into practice. So now is the time to prepare. We must continue to advocate for enforced limitations on embryo use and destruction before IVG becomes a clinical realization. As noted by Dr. Saitou and Dr. Hayashi, the original pioneers of IVG technology, the ethics must be rigorously considered “because such an application would change our understanding of human origins and the continuity of life.”

Final thoughts on IVG

“We shouldn’t pause science while we wait for the ethical issues to catch up.”

This statement was made by Dr. Paula Amato, a professor at OHSU and a lead author of the recent “mitomeiosis” study. There’s no question that scientific progress is vital. When guided by ethical principles, it expands our understanding of the world and drives meaningful advances in human health. But should we really move forward first and ask the ethical questions later, after harm has already been done? Are we willing to inflict deep wounds on human dignity in the name of innovation? Progress should not come at the cost of our moral lives.

There are still profound mysteries that control the very beginning of human life and questions science has yet to answer. These unknowns make IVG unfit for clinical use. For now. But how many embryos will be subjected to endless experimentation in the pursuit of biological knowledge that perhaps does not need to be revealed?

Research driving these technologies is often justified under the banner of women’s reproductive health. This is not women’s health. These studies divert critical funding away from research that could truly improve women’s lives and identify root causes of infertility. Even more troubling, IVG could further reduce women to unnecessary components of reproduction or relegate them to mere vessels for gestating lab-created life made from the DNA of two men.

And perhaps most alarming of all, we simply don’t know the long-term effects on children conceived through IVG. We are risking real lives and the future health of these children, all in the name of reproductive equity and scientific ambition. Embryos will be created and destroyed, treated as research material, all to fulfill the belief that having a child is a right that must be guaranteed no matter the ethical cost.

It is still possible that these technologies will never reach clinical use. That uncertainty makes vigilance more important than ever. That is why the Center for Bioethics and Culture remains at the forefront, confronting the ethical challenges of third-party reproduction head-on. We will not stand by and wait for ethics to catch up. Instead, we will lead the conversation, advocating for science that respects human dignity and defending the rights of women and the unborn every step of the way.

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