Male and Female Fertility: Prevention and Monitoring Hodgkin' Lymphoma and Diffuse Large B-Cell Lymphoma Adult Survivors. A Systematic Review by the Fondazione Italiana Linfomi

Simple Summary Patients with Hodgkin lymphoma or diffuse large B-cell lymphoma treated with chemotherapy, with or without radiation therapy on pelvic nodes, may suffer permanent damage to their reproductive function, which significantly affects their quality of life. Established gamete cryopreservation techniques, including the freezing of embryos, oocytes, spermatozoa, ovarian and testicular tissue, can, nowadays, be offered to any adult patient candidate receiving gonadotoxic therapy who is interested in preserving future fertility. In order to offer updated information on anticancer treatment harm and to better advise patients on fertility preservation options, Fondazione Italiana Linfomi (FIL) researchers conducted this systematic review to evaluate the frequency of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between end of treatment and conception in adult lymphoma patients. Background: Adult patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) have prolonged survival but face the risk of treatment-induced impaired fertility. This systematic review, conducted by Fondazione Italiana Linfomi (FIL) researchers, aims to evaluate the incidence of treatment-related infertility, fertility preservation options, fertility assessment measures, and the optimal interval between the end of treatment and conception. Methods: MEDLINE, the Cochrane Library, and EMBASE were systematically searched up to September 2020 for published cohort, case-control, and cross-sectional studies on fertility issues. Results: Forty-five eligible studies were identified. Gonadotoxicity was related to sex, type and dosage of treatment, and, in females, to age. After receiving alkylating-agent-containing regimens, less than 30% of males recovered spermatogenesis, and 45% of females >= 30 years in age retained regular menstrual cycles. Sperm cryopreservation was offered to the majority of patients; sperm utilization resulted in a 33-61% pregnancy rate. After ovarian tissue transplantation, the spontaneous pregnancy and live birth rates were 38% and 23%; after IVF, the live birth rate was 38.4%. No data could be extracted on the utilization rate of cryopreserved mature oocytes. The results of studies on GnRH analogs are controversial; therefore, their use should not be considered an alternative to established cryopreservation techniques. Sperm count, FSH, and inhibin-B levels were appropriate measures to investigate male fertility; serum AMH levels and antral follicle count were the most appropriate markers for ovarian reserve. No data could be found regarding the optimal interval between the end of treatment and conception. Conclusions: The risk of infertility should be discussed with adult lymphoma patients at the time of diagnosis, and fertility preservation options should be proposed before first-line treatment with alkylating-agent-containing regimens.