An artificial ovary — the female sex organ that produces eggs — may soon be achievable, say Danish researchers who have engineered a “scaffold” on which early-stage cells can develop into functional ovarian follicles, the small fluid-filled sacs that contain a woman’s eggs.
This represents further progress in preserving a woman’s fertility from the impact of cancer treatments, experts say.
Dr. Susanne Pors, a co-author of the study and postdoctoral fellow in the Laboratory of Reproductive Biology at the University Hospital of Copenhagen Rigshospitalet, will present the research Monday at the 34th Annual Meeting of the European Society of Human Reproduction and Embryology in Barcelona, Spain.
“The artificial ovary will consist of a scaffold (originating from the woman’s own tissue or from donated tissue) combined with her own follicles,” Pors wrote in an email. “It is newly constructed, but biological.”
A new option for fertility?
When a woman is diagnosed with cancer, she might want to consider how best to preserve her fertility, as both radiotherapy and chemotherapy, which are commonly used as cancer treatments, often destroy the function of her ovaries.
Two methods of fertility preservation are available. One option is to remove and freeze some of her eggs so that after her cancer has been treated and she’s ready for a child, she can attempt in-vitro fertilization. The second technique, commonly referred to as ovarian tissue transfer, involves removing ovarian tissue before treatment, freezing it and reimplanting it after treatment.
This second option is used less often than the first due to concerns that the ovarian tissue that is removed before treatment might contain malignant cells and, when it’s implanted, cancer could be reintroduced into a woman’s body.
This is why the American Society of Reproductive Medicine considers the procedure “experimental” — not fully safe. In the society’s published opinion, the risk of reintroducing malignancy is “currently unknown for most types of cancer,” although ovarian, leukemia and other blood-borne cancers are known to carry the greatest risk.
The new research is an attempt to remove the possibility of reintroducing cancer in the original tissue.
Pors and her co-authors theorized that if they could bioengineer an ovarian tissue scaffold that is free of cancer, they could seed it with previously frozen early-stage follicles, which then might develop and mature naturally. Ultimately, this could restore a woman’s fertility.
First, they experimented on human tissue donated by patients attempting fertility preservation. Using a three-day chemical process, the researchers eliminated all cells that could contain cancer from the tissue.
Follicles, unlike ovarian tissue cells, do not contain cancer, Pors said. “The follicle is formed during fetal life [when no cancer is present] and is surrounded by a basal membrane that does not allow cancer cells to penetrate,” she said.
The chemical process left a “decellularized scaffold” made up of proteins and collagens, the normal material that connect cells. The researchers seeded this structural matrix with early-stage follicles. As hoped, the material permitted communication between the cells and allowed them to develop.
This development occurred in vitro, or outside the body.
Next, the researchers experimented with mice and transplanted a decellularized and seeded matrix into the animals. This supported survival and growth of the early-stage follicles.
“This is the first time that isolated human follicles have survived in a decellularized human scaffold,” Pors and her co-authors concluded.
As a proof-of-concept, Pors said it could offer a new strategy in fertility preservation without risk of cancer reoccurrence.
More research needed
Daniel Brison, scientific director of the Department of Reproductive Medicine at the University of Manchester, said the new research is “a very interesting and novel” approach to fertility preservation. Brison, who was not involved in the study, noted that the use of decellularized scaffolds is common in regenerative medicine, where tissues derived from stem cells are transplanted back into patients.
He added that the new technique transplants only the eggs and surrounding cells of the follicle (seeded into a matrix) back into the uterus.
“This could give rise to a problem in itself, however, as the surrounding ovarian cells left behind might be required for the ovary to function fully,” Brison noted.
Though this approach might work, he concluded that “it is not possible to tell until the data from this research group have been peer-reviewed by the scientific community and published in a scientific journal.”
Dr. Richard Anderson, a professor and head of obstetrics and gynecology at the University of Edinburgh, said in a statement that an artificial ovary capable of supporting development of the follicle and the egg within it “would be very valuable scientifically” in that it would help scientists “develop new tests and perhaps treatments for infertility.”
“At this stage many questions remain,” said Anderson, who was not involved in the research. “But it is certainly a promising approach.”
About 2% of women of reproductive age who have cancer and go through treatment are at risk of losing their ovarian function — and thus their fertility. They are thrust into premature menopause, and although the use of hormone replacement therapy and their own cryopreserved eggs allows some of these women to become pregnant, their natural hormones and natural fertility will not be renewed.
For young female cancer patients wanting to preserve their fertility, ovarian tissue transfer that can restore menstrual cycles and allow the woman to get pregnant “the old-fashioned way” — since hundreds of eggs remain intact within the follicles — would be a huge advantage over freezing a few eggs.
A review published this year by Pors and her co-authors reported that a total of 318 women worldwide had undergone ovarian tissue transfers, with nine receiving a diagnosis of cancer afterward (in all cases not directly caused by the procedure). Renewed hormonal function occurred in 95% of these women, and more than 100 children have been conceived after the tissue transfers.