Young women with lymphoma may have lower ovarian reserve even before starting cancer treatment, and their ovarian reserve declines even further during chemotherapy, according to a study published in the journal Pediatric Blood & Cancer. Although ovarian function showed some recovery after treatment, ovarian reserve remained lower than expected one year later. Importantly, about one-third of participants had evidence of diminished ovarian reserve one year after treatment. 

Researchers also identified two factors that can help predict who is most likely to experience diminished ovarian reserve: having a low ovarian reserve at the time of lymphoma diagnosis and receiving higher doses of alkylating chemotherapy. These findings suggest that measuring ovarian reserve at diagnosis, before treatment begins, may help doctors and families better understand an individual patient’s potential fertility risks and make more informed, personalized decisions about fertility preservation, says lead author Lindsay Schwartz, MD, MS, a pediatric oncologist and physician-scientist at Ann & Robert H. Lurie Children’s Hospital of Chicago and Assistant Professor of Pediatrics (Hematology, Oncology, and Stem Cell Transplantation) at Northwestern University Feinberg School of Medicine. 

Key Takeaways

  • Fertility risks may exist before cancer treatment even begins. 
    The researchers found that girls and young women with lymphoma had lower levels of anti-Müllerian hormone (AMH)—a blood marker of ovarian reserve—than healthy peers even before receiving chemotherapy. This suggests that lymphoma itself may affect ovarian reserve, in addition to the effects of treatment. 
  • Chemotherapy can cause a substantial but not necessarily permanent drop in ovarian reserve. 
    AMH levels fell dramatically during treatment and began to recover after treatment ended. However, one year later, levels had not returned to pre-treatment. The researchers will need longer follow-up to understand how much additional recovery occurs over time. 
  • About one in three patients still had diminished ovarian reserve one year after treatment. 
    This is important because diminished ovarian reserve does not necessarily mean that someone cannot become pregnant. Rather, it may mean that she has fewer remaining eggs and may have a shorter reproductive window or potentially a lower response to fertility preservation techniques, such as egg retrieval and freezing. 
  • Researchers can identify some patients at particularly high risk. 
    Patients who already had a low AMH at diagnosis or who received higher doses of alkylating chemotherapy were much more likely to have diminished ovarian reserve after treatment. This information could help clinicians personalize fertility counseling rather than treating all patients with lymphoma as having the same fertility risk. 
  • There is still an opportunity to discuss fertility preservation after treatment. 
    Importantly, none of the participants had evidence of acute ovarian failure one year after treatment. Therefore, even when fertility preservation cannot happen before cancer treatment, it may still be worth discussing options such as egg freezing after treatment. The findings of the study reinforce the importance of having fertility conversations early and revisiting them throughout treatment and survivorship.    

Opportunities for Future Research 

The next step is to follow patients like these for a longer period of time to determine how ovarian reserve changes over several years after treatment and, ultimately, how these changes relate to real-world reproductive outcomes. “AMH is an important marker of ovarian reserve, but it cannot tell us exactly whether or when an individual patient will be able to become pregnant. Longer follow-up will help us better understand the connection between ovarian reserve, fertility potential, and future reproductive health,” says Dr. Schwartz.  

Dr. Schwartz also wants to build on this work by studying how newer lymphoma treatments affect fertility. “Most patients in this study received chemotherapy-based treatment, whereas today’s patients are increasingly receiving newer therapies, including targeted treatments and immunotherapy. We currently know very little about the effects of these treatments on ovarian reserve and future fertility,” she says. 

More broadly, Dr. Schwartz’s research is focused on developing a more personalized approach to fertility and survivorship care for children, adolescents, and young adults with cancer. This includes understanding which patients are at greatest risk for treatment-related late effects, identifying opportunities to preserve fertility, and ensuring that patients have access to appropriate fertility counseling and preservation options. Ultimately, the goal is to help young people not only survive cancer, but also have the opportunity to pursue life goals that matter to them, including having biological children if they choose to do so. 

Pediatric research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute.