Long-term follow-up to assess criteria for ovarian tissue cryopreservation for fertility preservation in young women and girls with cancer.
Long-term follow-up to assess criteria for ovarian tissue cryopreservation for fertility preservation in young women and girls with cancer.
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DOI：
10.1093/humrep/dead060
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发表时间：
2023-06-01
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爱丁堡选择标准是否正确识别了18岁以下有卵巢功能不全（POI）风险的女性癌症患者作为卵巢组织冷冻保存（OTC）的候选人？使用这些标准进行的患者评估准确地识别了那些有POI风险的患者，这些患者可以提供OTC和未来的移植作为生育力保护的手段。儿童癌症的治疗可能对未来的生育能力产生不利影响;在诊断时，应进行生育风险评估，以确定应向其提供生育能力保护的患者。爱丁堡的选择标准，根据计划的癌症治疗和患者的健康状况，用于确定那些在高风险，因此有资格为OTC。然而，该手术并非没有风险，并且关于该手术在青春期前患者中的疗效的数据很少。因此，有必要对生殖结果进行长期随访，以确保适当提供OTC。队列研究涵盖了1996年1月1日至2020年4月30日期间苏格兰东南部18岁以下被诊断患有癌症的所有女性。随访患者的生殖结局，以评估POI的诊断。共确定了638名合格患者; 12岁以下或12岁之前死亡的患者被排除在研究之外，留下431名患者的研究人群。审查电子记录的生殖功能，通过当前月经、妊娠（在没有POI诊断的情况下）、生殖激素测量、青春期进展或POI诊断进行评估。从分析中排除接受激素避孕的患者（除治疗POI或无性腺毒性治疗史的全垂体功能减退症外）（n = 9）。其余422例患者采用Kaplan-Meier方法进行分析，POI作为定义事件，采用考克斯比例风险模型。在431例患者的研究人群中，诊断和分析时的中位年龄分别为9.8岁和22.2岁。142例患者的生殖结局不可用;假设这些患者没有POI，但也进行了排除这些患者的亚组分析。在分析时年龄>12岁且未服用激素避孕药的422名患者中，37名患者接受了OTC治疗，25名患者成功接受了OTC治疗。在37名提供OTC的患者中（1名在复发时），9名（24.3%）发生POI。在386名未提供OTC的患者中，有11名（2.9%）发生了POI。接受OTC治疗的患者发生POI的概率显著更高（风险比[HR] 8.7 [95% CI 3.6-21]; P < 0.0001），即使将结局未知的患者排除在分析之外（HR 8.1 [95% CI 3.4-20]; P < 0.001）。所有接受OTC治疗的患者在治疗原发病后发生POI;在未接受OTC治疗的患者中，5例患者（45.5%）在治疗疾病复发后发生POI。大量患者的生殖结局未知;其中许多患者正在进行随访，但没有记录生殖评估。这可能给分析带来了偏差，并强调了生殖随访作为常规癌症治疗后护理的一部分的必要性。此外，患者人群年龄相对较小，在某些情况下随访持续时间较短，表明需要对该队列进行持续随访。儿童癌症后POI的患病率较低，但爱丁堡选择标准仍然是在诊断时选择高风险人群的有力工具，以提供适当的OTC。然而，需要更强化治疗的疾病复发仍然是一个挑战。本研究还强调了在血液学/肿瘤学随访中常规评估和记录生殖状态的重要性。K.D.由CRUK资助（C157/A25193）支持。这项工作的一部分是在医学研究理事会生殖健康中心进行的（由医学研究理事会赠款MR/N 022556/1支助）。R.A.A.已收到Ferring和Roche Diagnostics的咨询费; Merck和IBSA的教育活动费用; Roche Diagnostics的实验室材料。其他作者没有竞争利益需要声明。N/A.
Do the Edinburgh Selection Criteria correctly identify female cancer patients under the age of 18 who are at risk of premature ovarian insufficiency (POI) as candidates for ovarian tissue cryopreservation (OTC)? Patient assessment using these criteria accurately identifies those at risk of POI, who can be offered OTC and future transplantation as a means of fertility preservation. Treatment for childhood cancer can have adverse consequences on future fertility; at the time of diagnosis, fertility risk assessment should be undertaken in order to identify patients to whom fertility preservation should be offered. The Edinburgh selection criteria, based on planned cancer treatment and patient health status, are utilized to identify those at high risk and therefore eligible for OTC. However, this procedure is not without risk and there are few data on the efficacy of the procedure in prepubertal patients. As such, long-term follow-up of reproductive outcomes is necessary, to ensure that OTC is being offered appropriately. Cohort study encompassing all females diagnosed with cancer under the age of 18 in South East Scotland, from 1 January 1996 to 30 April 2020. Patients were followed up for reproductive outcomes to assess for diagnosis of POI. A total of 638 eligible patients were identified; patients under the age of 12 or deceased before the age of 12 were excluded from the study, leaving a study population of 431 patients. Electronic records were reviewed for reproductive function, assessed by current menstruation, pregnancy (in the absence of POI diagnosis), reproductive hormone measurements, pubertal progression, or diagnosis of POI. Patients on hormonal contraception (other than for treatment of POI or panhypopituitarism with no history of gonadatoxic treatment) were excluded from analysis (n = 9). Analysis on remaining 422 patients was carried out using the Kaplan–Meier methods, with POI as the defined event, and Cox proportional hazards model. In the study population of 431 patients, median ages at diagnosis and analysis were 9.8 and 22.2 years, respectively. Reproductive outcomes were unavailable in 142 patients; the assumption was made that these patients did not have POI, but a subanalysis excluding these patients was also performed. Of the 422 patients aged >12 at analysis and not taking hormonal contraception, OTC was offered to 37 patients and successfully performed in 25 patients. Of the 37 patients offered OTC (one at time of relapse), nine (24.3%) developed POI. Of the 386 not offered OTC, 11 (2.9%) developed POI. The probability of developing POI was significantly higher in those offered OTC (hazard ratio [HR] 8.7 [95% CI 3.6–21]; P < 0.0001), even when those patients with unknown outcomes were excluded from the analysis (HR 8.1 [95% CI 3.4–20]; P < 0.001). All patients offered OTC who developed POI did so after treatment for primary disease; in those not offered OTC, five patients (45.5%) developed POI after treatment for disease relapse. A significant number of patients had unknown reproductive outcomes; many of these patients were engaged in ongoing follow-up but did not have documented reproductive assessment. This may have introduced bias to the analysis and highlights the need for reproductive follow-up as part of routine cancer aftercare. In addition, the relatively young age of the patient population and short duration of follow-up in some cases demonstrates the need for ongoing follow-up of this cohort. The prevalence of POI after childhood cancer is low, but the Edinburgh selection criteria remain a robust tool for selecting those at high risk at the time of diagnosis, to offer OTC appropriately. However, disease relapse necessitating more intensive treatments remains a challenge. This study additionally highlights the importance of routine assessment and documentation of reproductive status in haematology/oncology follow-up. K.D. is supported by a CRUK grant (C157/A25193). This work was undertaken in part in the MRC Centre for Reproductive Health, (supported by MRC grant MR/N022556/1). R.A.A. has received consulting fees from Ferring and Roche Diagnostics; payment from Merck and IBSA for educational events; and laboratory materials from Roche Diagnostics. The other authors have no competing interests to declare. N/A.
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儿童癌症幸存者的非手术过早绝经和生殖影响：儿童癌症幸存者研究的报告。
影响因子：
6.2
作者：
Levine JM;Whitton JA;Ginsberg JP;Green DM;Leisenring WM;Stovall M;Robison LL;Armstrong GT;Sklar CA
通讯作者：
Sklar CA
影响因子：
51.1
作者：
Mulder, Renee L.;Font-Gonzalez, Anna;Tissing, Wim J. E.
通讯作者：
Tissing, Wim J. E.
影响因子：
51.1
作者：
Chow, Eric J.;Stratton, Kayla L.;Green, Daniel M.
通讯作者：
Green, Daniel M.
影响因子：
8.3
作者：
ESHRE Guideline Group on Female Fertility Preservation;Anderson RA;Amant F;Braat D;D'Angelo A;Chuva de Sousa Lopes SM;Demeestere I;Dwek S;Frith L;Lambertini M;Maslin C;Moura-Ramos M;Nogueira D;Rodriguez-Wallberg K;Vermeulen N
通讯作者：
Vermeulen N
DOI：
10.1093/humrep/det388
发表时间：
2014-01
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
Anderson RA;McLaughlin M;Wallace WH;Albertini DF;Telfer EE
通讯作者：
Telfer EE