A Population-Based Study of Fertility in Female Survivors of Young Adult Cancer

描述（由申请人提供）：2007年由尤尼斯·肯尼迪·施莱佛国家儿童健康和人类发展研究所召集的专家小组强调，需要在癌症幸存者的生育能力方面进行更多的研究。随着生存率的提高，越来越明显的是，许多挽救生命的癌症疗法会损害儿童癌症幸存者的生育能力。年轻成人癌症的幸存者也会受到影响，但这一人群中不孕症的发病率和患病率尚不清楚。我们建议进行一项以人群为基础的流行病学研究，以描述年轻成人癌症（20-39岁之间诊断的癌症）女性幸存者继发于化疗和放疗的性腺损伤风险。符合条件的癌症幸存者将通过屡获殊荣的格鲁吉亚癌症统计中心确定，该中心负责全州范围的格鲁吉亚综合癌症登记处和国家癌症研究所SEER计划的大都会亚特兰大监测流行病学和最终结果（SEER）登记处。居住在亚特兰大大都会的年轻成年癌症的育龄女性幸存者将有资格，他们接受不同癌症治疗的情况将根据医疗记录的摘要来确定。我们还将招募一个以社区为基础的对照组，由未接受过癌症治疗的妇女组成。评估不孕症的发病率和患病率是具有挑战性的，因为没有单一的结果测量真正捕捉受损的生育能力，并且在尝试怀孕之前，通常无法识别生育力低下。因此，我们将从两个目标概括的几个角度来评估生育率。首先，我们将评估癌症幸存者（n= 2，000）与未暴露女性（n= 1，000）的生育史。我们将使用深入的计算机辅助电话访谈（CATI）来收集有关影响生殖潜力的各种因素的数据，包括月经史、妊娠史、不孕症史和对孩子的渴望。第二，我们将评估癌症幸存者（n=750）与未暴露妇女（n=250）的当前生育能力，基于许多临床标志物，包括抗M|勒氏管激素水平、窦卵泡计数、卵巢体积和子宫体积。我们的建议在几个方面具有创新性。它改进了现有的研究，首先是基于年轻成年癌症幸存者的人口，其次是通过评估每个妇女生殖生命周期内的各种生育指标，并将这些信息与人口大子集中当前生育率的生物标志物的测量相结合，充分捕捉生育率的复杂性质。对于被诊断患有癌症的年轻女性来说，不同疗法对她们生育能力的潜在影响往往是一个重大问题，但目前，临床医生提供建议的信息有限。我们的建议将直接解决这一关键的知识差距。 公共卫生相关性：越来越明显的是，许多挽救生命的癌症疗法对儿童癌症幸存者的生育能力有害，但对年轻成人癌症（20-39岁之间诊断的癌症）治疗的潜在性腺毒性影响研究较少，尽管年轻成人癌症幸存者占癌症幸存者的比例较大。我们建议进行一项以人群为基础的流行病学研究，比较不同癌症治疗对年轻成人癌症育龄女性幸存者生育相关结局的影响，并与未暴露于癌症治疗的女性进行比较。我们将通过详细的计算机辅助电话访问来评估生育史，包括月经周期、不孕症和生育史（n= 3，000），并将通过测量抗M抗体来评估当前生育力。|在一个亚组人群中（n= 1，000），测定了勒氏管激素、窦卵泡计数和卵巢体积。

DESCRIPTION (provided by applicant): A 2007 expert panel convened by the Eunice Kennedy Shriver National Institute of Child Health and Human Development highlighted the need for more research in the area of fertility among cancer survivors. As survival rates have improved, it has become increasingly apparent that many life-saving cancer therapies impair fertility among childhood cancer survivors. Survivors of young adult cancers are affected as well, but the incidence and prevalence of infertility in this population is unknown. We propose to perform a population-based epidemiology study to characterize the risks of gonadal damage secondary to exposure to chemotherapy and radiation therapy in female survivors of young adult cancers (cancers diagnosed between the ages of 20-39). Eligible cancer survivors will be identified through the award-winning Georgia Center for Cancer Statistics, which operates both the statewide Georgia Comprehensive Cancer Registry and the Metropolitan Atlanta Surveillance Epidemiology and End Results (SEER) Registry of the National Cancer Institute's SEER Program. Reproductive age female survivors of young adult cancers living in Metropolitan Atlanta will be eligible, and their exposure to different cancer treatments will be determined based on abstraction of medical records. We will also recruit a community-based comparison group of women who were not exposed to cancer therapies. Evaluating the incidence and prevalence of infertility is challenging because no single outcome measure truly captures compromised fertility, and subfertility is usually unrecognized until pregnancy is attempted. Therefore, we will evaluate fertility from several angles summarized by two aims. First, we will assess the fertility history of cancer survivors (n=2,000) compared to unexposed women (n=1,000). We will use an in-depth computer assisted telephone interview (CATI) to collect data on a wide range of factors contributing to reproductive potential including, menstrual history, pregnancy history, infertility history, and desire for children. Second, we will assess current fertility of cancer survivors (n=750) compared to unexposed women (n=250) based on a number of clinical markers including anti-M|llerian hormone levels, antral follicle count, ovarian volume, and uterine volume. Our proposal is innovative in several areas. It improves upon existing studies first by being population based in young adult cancer survivors and second by fully capturing the complex nature of fertility by assessing a wide range of indicators of fertility across each woman's reproductive life span and combining this information with measurement of biomarkers of current fertility in a large subset of the population. For young women diagnosed with cancer, the potential effect of different therapies on their ability to have children is often a significant concern, but at present, clinicians have limited information with which to advise them. Our proposal will directly address this critical gap in knowledge. PUBLIC HEALTH RELEVANCE: It has become increasingly apparent that many life-saving cancer therapies are detrimental to the fertility of childhood cancer survivors, but the potential gonadotoxic effects of treatments for young adult cancers (cancers diagnosed between the ages of 20-39) have been less well studied despite the fact that survivors of young adult cancers make up a larger proportion of cancer survivors. We propose to perform a population-based, epidemiologic study of the effects of different cancer treatments on fertility- related outcomes in reproductive age female survivors of young adult cancers compared to women unexposed to cancer treatments. We will assess fertility history through a detailed computer assisted telephone interview on menstrual cycle, infertility, and reproductive history (n=3,000) and will assess current fertility by measuring anti-M|llerian hormone, antral follicle count, and ovarian volume in a subset of the population (n=1,000).