Every year, over 20,000 women of childbearing age are diagnosed with cancer. Cancer treatments often include chemotherapy regimens that damage other tissues and the ovaries and its eggs are particularly sensitive to such treatments. Consequently, many young, female, cancer survivors are infertile as a result of their cancer treatments, and suffer early menopause and ovarian failure.
Now an earth-shaking study by Egyptian and American scientists has shown that stem cell injections into the ovaries can rejuvenate them and restore the fertility of laboratory animals.
“This approach carries high promise to women with chemotherapy-induced and potentially other types of premature ovarian failure,” said Dr Sara Mohamed, lead researcher for this project.
Woman who must undergo chemotherapy are routinely advised to freeze their eggs before they undergo any cancer treatments. However this procedure is labor intensive and takes time, and in urgent cases, there is not enough time to preserve the patient’s eggs. This leaves the woman in the unsavory position of having to decide between her fertility or her life.
A procedure like the one used in this study might give female patients other options that do not force them to choose between the Scylla of their ability to have their own children and the Charybdis of their survival.
To date, this procedure has been successfully performed in laboratory mice. In this experiment, a clutch of eighteen laboratory mice were broke into three groups of six. One group of six female mice was treated with anticancer chemotherapeutic agents, followed by injections of bone marrow stem cells into their ovaries. The second group of six female mice also received chemotherapy, followed by injections of sterile saline into their ovaries. The third group, a control group, received injections of sterile saline into their ovaries without receiving prior treatments with chemotherapy.
One week after receiving their treatments, the stem cell-treated mice showed a significant increase in estrogen production. Since estrogen is a sex steroid hormone that is essential to ovulation, these results suggested that the menstrual cycles of the infertile mice was actually being reconstituted. Then a week later, mice in the stem cell-treated group showed regeneration of their ovarian tissue and increased numbers of ovarian follicles. Ovarian follicles produce the sex steroid hormones estrogen and progesterone and contain a single egg that matures during the follicular stage of the menstrual cycle and is potentially released during ovulation. These same mice, which had experienced ovarian failure as a result of chemotherapy, were able to mate with male mice, and eventually give birth to large litters of healthy mouse pups while those who had saline injections continued to suffer from reduced fertility of even infertility.
These treatments worked so remarkably well, that the members of the researcher team who were involved with this project want to move to human trials as soon as possible.
Dr Sara Mohamed, of Mansoura Medical School in Egypt, who served as the lead researcher of this project, said she had come up with the idea after meeting a 22-year-old cancer patient who had a high risk of infertility from chemotherapy. Dr. Mohamed said: “It was a very emotional for me so I decided to pursue it and work on it to figure it out. It [is] a very common problem based on statistics of cancer female diagnosis every year. “
Dr. Mohamed continued: “We inject[ed] stem cells in[to] the ovaries of mice which had chemotherapy and were damaged and we got very good ovarian function restoration in form of follicle number, hormonal production, and finally getting pregnant and having new pups, which was our ultimate goal. We are now working on translating that into clinical trials (for humans). This approach carries high promise to women with chemotherapy-induced and potentially other types of premature ovarian failure.”
Imperial College gynecologist Stuart Lavery said: “This is very exciting piece of research that adds to our understanding of how cells differentiate to become egg stem cells.” Dr. Lavery served as a consultant on this research. I must add at this point as an aside that it is rather unlikely that the bone marrow stem cells are differentiating into eggs. Instead the bone marrow stem cells are probably augmenting the survival and health of existing eggs in the ovary.
Dr. Lavery continued: “Clearly, there remains an enormous amount of work to see whether these results would be transferable into humans. But it does provide some realistic hope that post-chemotherapy patients who have been made menopausal could one day restore ovarian function and possibly fertility.”
Dr. Mohamed and her colleagues would like to initiate human trials using umbilical cord or even embryonic stem cells. They will need to convince regulatory agencies that the procedures they have designed are safe. For this reason, I find it unlikely in the extreme that the US Food and Drug Administration (FDA) would give approval for an embryonic stem cell-based trial in the ovaries, given the large numbers of regulatory and safety hurdles other recent embryonic stem cell-based trials have had to conquer. Also, it is worth noting that the FDA has not approved other proposed trials that sought to stimulate ovarian-based stem cells. For this reason, getting FDA approval for their trial might prove difficult. Also, one mouse experiment is not going to be enough to persuade the FDA to acquiesce to their proposals. Large experiments will need to be done and large animals studies would also be needed as well.
Women who opt to freeze their eggs can use in vitro fertilization (IVF) to have their own children. Alternatively, if the eggs are fertilized with her mate’s sperm, then the embryos can development to the blastocyst stage after which they are cryopreserved (frozen) before chemotherapy for later family-building purposes.
Such a strategy leads to some problems in countries with nationalized medicine: some provinces have decreased funding for IVF, since IVF is very expensive and the demand is below the cost to maintain such faculties. Likewise, at times, female cancer patients are denied the option of cryopreservation, again because of the costs and the lack of a nearby facility that has the space, means, or funding to keep her embryos on ice for a time. A new regenerative therapy might give such a female patient some solace with regards to her future fertility.
A consultant in Reproductive Medicine and Surgery at Hammersmith Hospital, London, Dr Geoffrey Trew, said of this research: “Fertility-wise, if this works it would be stupendous. Certainly it does appear promising and anything you can do to regenerate and ovary is a good thing. Theoretically if you are regenerating the ovary you should be getting better quality eggs. Clearly we’re not here yet, and it’s good that the researchers are not over-claiming their findings, but it’s a great proof of concept.”
Dr Edgar Mocanu, consultant gynecologist at Rotunda Hospital in Dublin and a board member of the International Federation of Fertility Societies, said: “This could open phenomenal opportunities for women. Millions of women around the world undergo cancer treatment and some of them will become infertile through ovarian failure. While cancer survival rates have increased dramatically, to date there is no effective method of preventing infertility after chemotherapy. It could also open new avenues for the treatment of menopause induced health issues.”
Dr Owen Davis president of the American Society for Reproductive Medicine: “If this experimental treatment can be translated to women who have lost ovarian function from chemotherapy, it will be a great advance. Restoring ovarian hormone production, follicle development and fertility to chemotherapy patients is a potential new application for bone marrow donation that could help many women.”