Gonadal Function Recovery and Fertility in Women Treated with Chemo- and/or Radiotherapy for Hodgkin’s and Non-Hodgkin Lymphoma

Abstract

Background: Fertility and gonadal function represent one of the most important aspects for long-term lymphoma survivors. Aims: The aim of our study was to determine possible risk factors, such as age at treatment, chemotherapeutic regimen, protection with oral contraceptives (OCs), and gonadotropin-releasing hormone (GnRH) analogues in female patients treated for Hodgkin’s lymphoma (HL) or non-Hodgkin lymphoma (NHL) at a reproductive age. Methods: Patients between the age of 16 and 50 years at the time of HL or NHL diagnosis were selected. Eligible patients were requested to respond to a questionnaire by phone interview about fertility, menstrual status, sexual aspects, and treatment with OCs or GnRH analogues during chemotherapy. Results: The resumption of menstrual activity was associated with the use of the OCs and GnRH analogues during chemotherapy (p = 0.008 and 0.034, respectively). At univariate analysis, the use of OCs during chemotherapy was associated with a lower risk of amenorrhea (prevalence ratio [PR] = 0.37; 95% CI 0.17–0.82). A higher age at the time of treatment correlated positively with therapy-induced amenorrhea, with a difference of 12.8 years between the mean age at diagnosis of the women with therapy-induced amenorrhea and those who resumed their menses. Amenorrhea was significantly higher in women receiving R-CHOP than in women treated with ABVD (PR = 6.00; 95% CI 2.32–15.54). Moreover, NHL had an infertility PR of 1.51 (95% CI 0.86–2.45) at multivariate analysis compared to HL. Conclusions: This study suggests a possible role of pharmacological prophylaxis with OCs and GnRH analogues.

Fertility Preservation in Female Pediatric Patients With Cancer: A Clinical and Regulatory Issue

“…Several prospective non-randomized studies have shown the ability of GnRHa to provide a powerful instrument for protection of the ovarian function even in adolescents with hematological malignancies (88,96,99,101,105).…”

GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation

“…The study found that GnRHa co-treatment significantly decreased the POF rate from 33% to 82%. Moreover, a recent single-center retrospective study on postmenarchal adolescent patients (median age 14, range 11 to 18) treated for acute lymphoblastic leukemia, acute myeloid leukemia, Hodgkin's lymphoma, and other cancers showed that co-treatment with GnRH analogues preserved ovarian function and fertility in adolescents [65]. Other large retrospective and prospective studies, as well as case series, also showed a potential protective effect of GnRHa during chemotherapy in women with hematological malignancies [40,61,63,[65][66][67][68].…”

“…Gini et al [65] 97 pre-menopausal women with Hodgkin's and non-Hodgkin's lymphoma undertaking chemotherapy with or without GnRHa co-treatment. Data collected up to 2012.…”

Chinese expert consensus on clinical practice of female fertility preservation

“…The 15-year survival rates are 94%, 91%, and 87% in patients aged 18 to 29 years, 30 to 39, and 40 to 49 years, respectively [9] . The overall 5-year survival rate of non-Hodgkin's lymphoma is approximately 65%, but the prognosis of different subtypes varies greatly [10] . Chemotherapy is currently the main treatment for Hodgkin's lymphoma, and the common chemotherapy regimens include Common chemotherapy regimens for non-Hodgkin's lymphoma, such as cyclophosphamide + doxorubicin + vincristine + prednisone (CHOP) and rituximab-CHOP, confer a high risk of POI.…”