Artificial Ovaries Could Provide Safer HRT, Fertility Treatments

Ovarian Tissue and Human Egg

As organs fail, and with limited donors, scientists are keen to create artificial organs in the lab. In the latest advances, researchers have made progress creating artificial ovaries, a technology that could one day help restore fertility and act as a safer, drug-free alternative to hormone replacement therapy (HRT).

The study comes from Marie-Madeleine Dolmans of the Université Catholique de Louvain in Belgium, and colleagues, and was published in the Journal of Assisted Reproduction and Genetics. One of the major challenges with artificial organs is getting the structure just right, and ovaries have a particular composition that can be hard to mimic in the laboratory. These researchers set out to create an artificial ovary prototype that was close to natural human ovarian tissue in architecture and rigidity.

Current Ovarian Replacement Technology

When a woman undergoes radiation or chemotherapy, one concern is fertility. Often younger women will face these cancer treatments before they have a chance to start a family, but the harsh treatments can take their toll on delicate tissues such as the ovaries. The same treatments that help destroy the cancer can also destroy ovarian cells, making it difficult or impossible to conceive once the cancer treatments are complete.

There is a way to help women preserve their fertility during treatment: cryopreservation. Using this technology, a medical team will store the patient’s own ovarian tissue before radiation or chemotherapy, then once the treatment is complete and she is in remission, transplant the ovarian tissue back into her body.

This current technique has helped 130 cancer survivors conceive and give birth, but there is a catch: not everyone is suitable for this fertility restoration technique. When a patient has a risk of having malignant cells in their frozen tissue, the doctors cannot place the ovarian tissue back in her body since that could cause the cancer to return. This leaves too many aspiring mothers with few choices as they face their battle with cancer.

New Hope for Post-Cancer Fertility

For the women who cannot accept their removed ovarian tissue, options are limited, but new research provides hope. Ms. Dolmans and colleagues may have just found a way to give them an artificial ovary, based on their own tissue.

First, the researchers removed and froze mouse ovarian tissue, similar to the current techniques for preserving fertility. Later, the scientists isolated follicles from the tissue and encapsulated the follicles within a fibrin scaffold which they grafted to the patient. This scaffolding is made from filamentous protein which blood clots form around, giving follicles a place to settle, produce estrogen, and form mature egg cells. If the fibrin scaffold closely mimics the structure and physical properties of the ovary, it could support follicle growth. With restored follicle growth, the women could once again produce eggs, restoring their fertility after cancer treatment.

Although the researchers studied mice, they believe the same techniques could work in humans. They analyzed ovarian tissue from three women of child-bearing age using a scanning electron microscope. They analyzed the layer thickness, tissue stiffness, and other characteristics of the natural ovarian tissue, then compared that with different fibrin concentrations. They identified the fibrin formulation that most closely matched the architecture, porosity, and rigidity of the human ovary. This particular fibrin matrix is the best candidate for producing an artificial ovary in the future.

Once the researchers do produce an artificial ovary, there are many potential applications. Not only could the technology help restore fertility after chemotherapy or radiation therapy, it could also help women who are affected by infertility for other reasons. The ability to support follicle growth could also help women produce the estrogen they need to maintain a hormonal balance.

Lab-engineered Ovaries to Replace HRT

The Belgian researchers are not the only ones looking into creating artificial ovaries to help women: a team of researchers at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina, investigated the difference between hormone replacement therapy using hormonal drugs versus laboratory-made ovaries.

Although hormone replacement therapy can be an effective way to manage menopause symptoms, it does have its drawbacks. Taking drugs to compensate for lower natural sex hormone production can increase the risk of breast cancer and heart disease, so doctors do not recommend the treatment for long-term use. As an alternative, Emmanel Opara and team decided to look into using bioengineered artificial ovaries as an alternative hormone source. Instead of pills, injections, or topical gels with a set dose of hormones, cell-based hormone replacement might more closely match the hormone dose to the body’s needs, making it a more customized and therefore safer HRT method.

To test this HRT method, the researchers first isolated theca and granulosa cells from rat ovaries, then used a thin membrane to encapsulate the cells. The scientists then implanted this bioartificial ovary in rats who had no ovaries. These rats were compared with groups of rats who received a high or low dose of hormone replacement drugs, who were untreated, or who had normal ovarian function, as far as body composition, bone health, and uterine health. These three indicators reflect the body’s response to loss of ovarian function.

Effect of Artificial Ovaries on Body Composition

Previous research had established the link between loss of ovarian function and body fat accumulation as well as weight gain. When the researchers compared the rat groups for these indicators, they discovered the rats with artificial ovaries had similar body-fat levels to animals with intact ovaries. However, the rats with low-dose drug therapy had higher body fat percentage than these two groups. This seems to indicate the artificial ovaries kept hormone levels appropriate to normal body-fat levels, similar to natural ovaries.

Effect of Artificial Ovaries on Bone Health

As estrogen levels drop, osteoporosis can occur, increasing the risk of bone fracture. When the researchers compared the rats with artificial ovaries to those on hormone replacement drugs, they discovered the artificial ovary rats had better bone outcomes. This seems to indicate the artificial ovaries kept hormone levels appropriate to normal bone health.

Effect of Artificial Ovaries on Uterine Health

As ovarian function is lost, it can affect the genital and urinary system, leading to issues such as sexual dysfunction and urinary incontinence. When the researchers examined uterine tissue in the artificial ovary rats, they discovered uterine health similar to that of the rats with intact ovaries. This seems to indicate the artificial ovaries were able to maintain appropriate hormone levels for a healthy urogenital system.

Are Artificial Ovaries Available Soon?

The Wake Forest Baptist study is encouraging, offering a more targeted hormone replacement option to hormone drugs. These artificial ovaries could potentially help women maintain their usual hormone levels without the risks associated with hormone replacement. That said, there are some limitations. The current study involved rats, so future studies would need to be on humans and ensure long-term safety and effectiveness. Although women needing hormone therapy would not likely have enough ovarian cells for transplantation, donor cells could be an option. The researchers designed their artificial ovary capsule to allow oxygen and nutrients in while preventing the patient’s body from rejecting the cells, so donor ovarian tissue could potentially work to create the bioartificial ovaries. The Université Catholique de Louvain study is also encouraging, suggesting researchers may have found just the right structure to create an artificial ovary from a woman’s own preserved tissue.

That said, artificial ovaries are still in their experimental stages. It could take a while before the technologies are proven and available for everyday use. When they are, doctors like you may have a better option for helping women facing cancer treatments, affected by infertility, or going through menopause.

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