Viviani Simonetta, Caccavari Valentina, Gerardi Chiara, Ramadan Safaa, Allocati Eleonora, Minoia Carla, Guarini Attilio, Di Russo Anna
Division of Onco-Hematology IEO, European Institute of Oncology IRCCS, 20141 Milan, Italy.
Assisted Reproduction Unit, Istituto Clinico Città Studi, 20131 Milan, Italy.
Cancers (Basel). 2021 Jun 9;13(12):2881. doi: 10.3390/cancers13122881.
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.
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.
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.
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.
成年霍奇金淋巴瘤（HL）和弥漫性大B细胞淋巴瘤（DLBCL）患者生存期延长，但面临治疗导致生育能力受损的风险。由意大利淋巴瘤基金会（FIL）研究人员进行的这项系统评价旨在评估治疗相关不孕症的发生率、生育力保存选择、生育力评估措施以及治疗结束与受孕之间的最佳间隔。
截至2020年9月，系统检索了MEDLINE、Cochrane图书馆和EMBASE，以查找已发表的关于生育问题的队列研究、病例对照研究和横断面研究。
确定了45项符合条件的研究。性腺毒性与性别、治疗类型和剂量有关，在女性中还与年龄有关。接受含烷化剂方案治疗后，不到30%的男性恢复精子发生，45%年龄≥30岁的女性保持规律月经周期。大多数患者接受了精子冷冻保存；精子利用导致的妊娠率为33%-61%。卵巢组织移植后，自然妊娠率和活产率分别为38%和23%；体外受精后，活产率为38.4%。关于冷冻保存的成熟卵母细胞利用率，无法提取数据。关于促性腺激素释放激素类似物（GnRH）的研究结果存在争议；因此，不应将其使用视为既定冷冻保存技术的替代方法。精子计数、卵泡刺激素（FSH）和抑制素B水平是调查男性生育力的合适指标；血清抗缪勒管激素（AMH）水平和窦卵泡计数是卵巢储备的最合适标志物。未找到关于治疗结束与受孕之间最佳间隔的数据。
应在诊断时与成年淋巴瘤患者讨论不孕风险，并应在含烷化剂方案一线治疗前提出生育力保存选择。
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