By Rebecca Elstrom, MD and Glenn Schattman, MD
Dr. Elstrom is an Assistant Professor of Medicine at Weill Cornell Medical College whose clinical and research interests focus on the treatment of patients with lymphoma. Dr. Schattman is an Associate Professor of Obstetrics and Gynecology at Weill Cornell Medical College, specializing in reproductive endocrinology/infertility.
Preservation of fertility is a major concern in many patients with lymphoma, as many patients are within their child-bearing years at diagnosis. Furthermore, many young patients with lymphoma have a significant chance of being cured, making consideration of quality of life issues after lymphoma a critical aspect of care. Reliable data regarding the likelihood of infertility after chemotherapy however, have been difficult to come by. While many women may regain their menstrual cycles and possibly fertility, premature ovarian failure (POF), or menopause before age 40, can shorten the window of potential child-bearing following cancer treatment. Unfortunately, most studies use resumption of menstrual bleeding as a measure of fertility, though it is not a reliable indicator.
These issues are particularly relevant to patients with Hodgkin lymphoma, as peak incidence occurs at approximately 20 years of age, and most patients, even those with advanced stage disease, are cured. A paper recently published in the Journal of Clinical Oncology presented encouraging results for young women treated with ABVD chemotherapy, which is currently the standard approach in the United States. This study reviewed the reproductive outcomes of a subset of female patients treated on clinical trials within the European Organisation for Research and Treatment of Cancer (EORTC), and found that women less than age 32 who were treated with non-alkylating chemotherapy (such as ABVD) had no increased risk of POF (overall incidence 3%, similar to women in the general population), whereas those older than 32 years had a moderately increased risk of POF (9%). In contrast, women treated with alkylator-containing therapy, such as MOPP or BEACOPP, experienced a high rate of POF regardless of age, with an overall incidence of 60%.
Although this large cohort evaluation has shed light on the incidence and risk factors for POF in women with Hodgkin lymphoma, the data in women treated for non-Hodgkin lymphoma (NHL) are less clear. Standard therapy for Diffuse Large B-cell Lymphoma (DLBCL), the most common aggressive lymphoma, is R-CHOP, which contains cyclophosphamide, an alkylating agent. Small observational studies have not suggested a significant risk of absolute infertility following R-CHOP therapy; that is, most women regain menstrual function following therapy. However, for the most part, these studies do not address the risk of POF.
Strategies to maintain the possibility of child-bearing following chemotherapy are not standardized. Some investigators have explored the use of gonadotropin releasing hormone (GNRH) analogs during chemotherapy, with the idea that suppression of function of the reproductive organs may protect them from the effects of chemotherapy. Although some small studies have suggested this might be a useful strategy, other larger studies have shown no benefit, and this approach is not universally accepted. Other strategies which have a proven track record are available but require time for a cycle of ovarian stimulation and egg harvesting (2-3 weeks). Additionally, removal and freezing of ovarian tissue with subsequent transplantation has resulted in the birth of children although the efficiency of this technique is unknown and requires 2 surgeries. With the exception of in vitro fertilization and embryo freezing, which requires the presence of a male partner or donated sperm for fertilization, these strategies are in the early stages of development.
For men, the issues surrounding fertility are similar, but with different considerations. Alkylating agents are similarly more likely to induce infertility in men (with nearly universal loss of production of active sperm in a study of male fertility after BEACOPP), but non-alkylator-based chemotherapy is unlikely to cause infertility. Sperm banking is available and unlikely to require delay of chemotherapy, but it can be expensive. The rate of sperm recovery from a testicular biopsy in men who have no sperm after chemotherapy can be as high as 37%, allowing a potential alternative for those unable to bank sperm prior to therapy.
We at Weill Cornell recognize the critical importance of preservation of fertility to our younger patients with lymphoma. We have partnered with physicians at the Center for Reproductive Medicine (CRMI) here at New York-Presbyterian Hospital to provide timely consultation for our patients facing this issue in order to ensure that optimal and current information regarding fertility issues are available to patients prior to initiating potentially life-saving treatment for lymphoma. While focusing on our goal of developing new and better therapies to increase the chance of cure or long term survival, we are committed to preserving the quality of our patients’ lives after lymphoma treatment.