Australian researchers have discovered that a type of immunotherapy commonly used to treat cancer may cause fertility issues in women.
Led by a team from Monash University’s Biomedicine Discovery Institute and WA’s Peter MacCallum Cancer Centre, the pre-clinical trial showed that immune checkpoint inhibitors resulted in permanent damage to mouse ovaries and the eggs stored inside.
Specifically, the results, published August 25th in Nature Cancer, demonstrated that checkpoint inhibitors reduced the number and quality of the eggs, interfered with ovulation, and disrupted the fertility cycle, suggesting that these treatments could also affect the future fertility and hormonal health of women fighting cancer.
Traditional cancer therapies, such as chemotherapy and radiotherapy, have already been linked to permanent, negative side effects on the ovaries, potentially leading to infertility and premature menopause in young women and girls.
Yet until now, the potential fertility side effects of checkpoint inhibitor immunotherapy, an emerging and increasingly common cancer treatment that stimulates the immune system to enhance a patient’s ability to fight cancer, were unknown.
Lead author Lauren Alesi, a PhD candidate at Monash’s Biomedicine Discovery Institute Ovarian Biology Laboratory, explained that their research demonstrated that immune checkpoint inhibition increased immune cell infiltration and tumour necrosis factor-α expression within the ovary, diminished the ovarian follicular reserve and impaired the ability of oocytes to mature and ovulate.
“Initially these treatments were thought to be less damaging (than chemo and radiotherapy) in the context of off-target effects to the body in general, however, it is now clear that inflammatory side effects in other organ systems are quite common with these drugs,” Ms Alesi said.
“Our study highlights that caution should be exercised by clinicians and their patients, for whom fertility may be a concern. Studies in women receiving these drugs must now be prioritised.”
Senior author and head of the Translational Breast Cancer Genomics and Therapeutics Laboratory at the Peter MacCallum Cancer Centre, Professor Sherene Loi, said further research into how these drugs impact the ovarian function and fertility must be prioritised and included in future clinical trials involving women of reproductive age.
“Immunotherapy is now becoming a standard of care for many women with curable early-stage breast cancer, due to impressive results in reducing breast cancer recurrences, but further research into the long-term effects of immunotherapy is needed,” Professor Loi said.
“Our study further highlights that fertility discussions are critical for all age-appropriate women who are recommended to receive chemotherapy as well as immunotherapy.”
The findings have also prompted the authors to call for more preventative measures for women using checkpoint inhibitors.
“Apart from drugs that block ovaries from producing hormones during chemotherapy, and strategies to prevent premature menopause in younger women, egg and embryo freezing is the only fertility preservation measure available,” Ms Alesi said.
“[However], it is important to remember that embryo freezing is expensive, invasive and does not prevent ovarian damage, which means that premature menopause could still be a risk for these women.
“Therefore, we are now prioritising investigation of targeted ovarian preservation strategies that aim to prevent the damage to the ovary from occurring in the first place, without interfering with the drugs’ ability to fight the cancer.”
Ms Alesi highlighted that other immunotherapy classes should also be assessed in light of their study’s findings.
“Our results may have implications for other immunotherapies, since our results have revealed a close relationship between immune cells, the communication molecules (cytokines) they release, and regulating many aspects of fertility,” she said.
“Appropriate interventions that can preserve fertility and ovarian function can be implemented to facilitate pregnancies in the future, post completion of treatment. These interventions need to be implemented in a timely manner, so as not to delay anti-cancer treatment.”