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
by
, ,
Simonetta Viviani
1,*
,
Valentina Caccavari
2,
Chiara Gerardi
3,
Safaa Ramadan
1,4,
Eleonora Allocati
3,
Carla Minoia
5
,
Attilio Guarini
5 and
Anna Di Russo
6 1
Division of Onco-Hematology IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy
2
Assisted Reproduction Unit, Istituto Clinico Città Studi, 20131 Milan, Italy
3
Istituto di Ricerche Farmacologiche “Mario Negri” IRCCS, 20156 Milan, Italy
4
Department of Medical Oncology, National Cancer Institute, Cairo University, 11796 Cairo, Egypt
5
Hematology Unit—IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
6
Department of Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(12), 2881; https://doi.org/10.3390/cancers13122881
Submission received: 1 May 2021
/
Revised: 2 June 2021
/
Accepted: 5 June 2021
/
Published: 9 June 2021
(This article belongs to the Special Issue Lymphoma Survivorship)
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.
Abstract
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.
