Some immunotherapy treatments may damage female fertility

Australian researchers have discovered that some immunotherapy treatments used to treat cancer could affect the future fertility and hormonal health of female cancer survivors, prompting experts to call for more research and preventative measures, such as freezing eggs. Their results have been published in the journal Nature Cancer.

Traditional cancer therapies, such as chemotherapy and radiotherapy, are already linked to permanent, negative side effects on the ovaries. This can lead to infertility and premature menopause in young girls and women. But until now the potential fertility side effects of immunotherapy, an emerging and increasingly common cancer treatment that stimulates the immune system, have been unknown.

Led by the Monash Biomedicine Discovery Institute and the Peter MacCallum Cancer Centre, the new study found that a type of immunotherapy called immune checkpoint inhibitors, which ‘release the brakes’ on the immune system to enhance a patient’s ability to fight cancer, resulted in permanent damage to mouse ovaries and the eggs stored inside. Its authors said studies in female patients were now needed to investigate the findings; in the meantime, fertility preservation through egg or embryo freezing should be considered for women using these immunotherapies.

“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,” said co-lead author Lauren Alesi, a PhD candidate in the Monash Biomedicine Discovery Institute Ovarian Biology Laboratory. “However, it is now clear that inflammatory side effects in other organ systems are quite common with these drugs.

“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.”

Peter MacCallum Professor Sherene Loi, a senior author on the study, said further research into how these drugs impact the ovarian function and fertility of women receiving these drugs must be prioritised and should be included in future clinical trials involving women of reproductive age.

“Our study further highlights that fertility discussions are critical for all age-appropriate women who are recommended to receive chemotherapy as well as immunotherapy,” Loi 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.

“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.”

Apart from drugs that block ovaries from producing hormones during chemotherapy, and strategies to prevent premature menopause in younger women, Alesi said egg and embryo freezing was the only fertility preservation measure available. She said it was important to remember that embryo freezing is expensive and invasive, and does not prevent ovarian damage, meaning 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,” she said, adding that other immunotherapy classes also need to be assessed.

“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 concluded.

Image caption: Mouse eggs. Image credit: Dr Jessica Stringer.

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