Gonadal toxicity can be a side effect of chemotherapy and radiation therapy. However, a recent study in Denmark confirms what many physicians have suspected: Ovarian tissue cryopreservation and transplantation is a safe, effective method of preserving fertility.
Whether or not a woman becomes infertile during cancer treatment depends on a variety of factors, including her age at the time of diagnosis, the age at which she decides to have a child, the chemotherapy agents used during treatment and the dosage of medication delivered, according to the American Cancer Society. These considerations make it difficult to estimate how many women are able to become pregnant without infertility treatment following cancer therapy. However, women who undergo chemotherapy or radiation therapy may face infertility or premature ovarian insufficiency.
Means of preserving fertility after cancer treatment include oocyte retrieval, oocyte and/or embryo cryopreservation, and ovarian tissue cryopreservation and transplantation. More outcomes data is available on oocyte and/or embryo cryopreservation, so this is typically the method of choice. However, these modalities require delaying cancer treatment for up to two weeks. For women who need to undergo immediate gonadotoxic treatment and for prepubescent girls, ovarian cryopreservation and transplantation represents a viable alternative.
During the cryopreservation procedure, physicians laparoscopically remove one ovary prior to the initiation of cancer treatment. The 1-millimeter fibrous outer cortex of the ovary, which contains the primordial follicles, is removed and cut into small sections that typically range from 0.3 to 2 millimeters in thickness, according to the American Society for Reproductive Medicine. The tissue is then frozen and preserved, and once a woman has completed her cancer treatment, the preserved tissue is transplanted onto the remaining ovary.
Examining Long-term Efficacy Data
The Human Reproduction-published study followed 41 Danish women who had at least one ovarian transplantation procedure from 2003 to June 2014. According to inclusion criteria, the women were younger than 35 at the age of ovarian cryopreservation, had a greater than 50 percent chance of developing premature ovarian insufficiency following treatment and had a greater than 50 percent chance of five-year survival.
At the time the research was published, 12 study participants had given birth to a total of 14 children. However, Professor Claus Yding Andersen, DMSc, of Copenhagen University Hospital, notes the rates may increase because the ovarian tissue was still functional in some cases, which could result in future pregnancies.
“The functional duration [of the ovarian tissue] is very variable and depends on a woman’s age, her ovarian reserve, our freezing technique and probably factors that we are not quite aware of at the moment,” says Dr. Andersen, a study author. “Usually, [the tissue] lasts several years. We have two women in whom the tissue lasted more than 10 years and some in whom [tissue function] barely came back.”
Implications for Future Applications
Even though ovarian cryopreservation and tissue transplantation has been performed for many years, little data on its effectiveness exists. One of the benefits of this study is that it provides a denominator — physicians now have firmer data on which to gauge how effective the procedure is, according to Glenn L. Schattman, MD, Associate Professor of Clinical Obstetrics and Gynecology and Clinical Reproductive Medicine at the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine at Weill Cornell Medical College in New York, who was not involved in the research.
The study also answered the lingering question of whether or not transplanting ovarian tissue into women after cancer treatment increases the risk of cancer recurrence. Of the 41 women who received transplanted tissue, only three had a cancer relapse, and the relapse was unrelated to the procedure.
“We are extremely excited about the fact that none of the women had a [procedure-related] relapse,” Dr. Andersen says. “The tissue is harvested at a time when [women] have a potentially deadly disease, and if we transplanted the disease through the ovarian tissue and [they] had a relapse, this would mean a no-go for this technique.”
Despite the positive results, Dr. Schattman doesn’t believe this procedure will become more widely utilized because it is still considered experimental and isn’t covered by insurance, at least in the United States. He believes that may change if more positive outcomes data are published, but notes that developing fertility-preserving treatments may be an even better aspiration for clinicians.
“There are some new treatments down the line that are gonadoprotective, so [women] may be able to get chemotherapy with other treatments that protect the eggs in ovaries,” Dr. Schattman says. “The goal, hopefully, is that we will never have to freeze ovarian tissue. We will be able to provide treatment for people that won’t affect their fertility, so they won’t face that stress.”