Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen K, Denmark.
Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen NV, Denmark.
Hum Reprod. 2019 Nov 1;34(11):2290-2296. doi: 10.1093/humrep/dez165.
STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.
研究问题:辅助生殖技术(ART)治疗期间的激素刺激是否会增加卵巢癌的风险?
总结答案:除了患有子宫内膜异位症的 ART 治疗女性外,ART 治疗女性并未发现卵巢癌风险增加。
已知情况:先前关于 ART 期间卵巢刺激与卵巢癌之间关联的研究结果存在冲突。卵巢癌的风险因不孕原因而异,只有少数关于 ART 治疗和卵巢癌风险的研究有足够的数据来解决这个问题。子宫内膜异位症与卵巢癌风险增加有关。
研究设计、规模、持续时间:1994 年至 2015 年间接受 ART 治疗的女性在丹麦 IVF 登记处登记。使用分配给丹麦居民的个人身份号码,将数据与丹麦癌症登记处和社会人口学人群登记处的数据进行链接。
参与者/材料、地点、方法:所有接受 ART 治疗的女性均与女性背景人群的随机样本进行年龄匹配,并随访长达 22 年。经过相关排除后,该人群包括 58472 名接受 ART 治疗的女性和 625330 名未接受治疗的女性,均无先前的恶性肿瘤。使用多变量 Cox 回归分析评估卵巢癌风险,并根据教育程度、婚姻状况、产次和治疗年份进行调整。结果显示为风险比(HR)及其相应的置信区间。
主要结果和机会的作用:在随访期间(平均 9.7 年),共有 393 名(0.06%)女性被诊断为卵巢癌。接受 ART 治疗的女性卵巢癌风险增加(HR 1.20,95%CI 1.10-1.31),随着时间的推移风险逐渐降低。这种风险在患有女性因素不孕的女性中更为明显(HR 1.36,95%CI 1.25-1.48),而没有女性因素不孕的女性风险较低(HR 0.87,95%CI 0.76-1.00)。患有子宫内膜异位症的女性风险增加(HR 3.78,95%CI 2.45-5.84),而接受 ART 治疗且患有多囊卵巢综合征、其他女性不孕原因和不明原因不孕的女性风险并未增加。
局限性、谨慎的原因:ART 治疗与卵巢癌之间的关联可能因 ART 治疗期间多次超声扫描导致的检测增加而受到影响。
研究结果的更广泛意义:在没有子宫内膜异位症的情况下接受 ART 治疗与卵巢癌风险增加无关,这令人安心。ART 治疗是否会增加患有子宫内膜异位症的女性的卵巢癌风险仍需进一步研究。
研究资金/利益冲突:这项工作得到了丹麦哥本哈根大学健康与医学科学学院博士学位授予给 D.V.的资助。丹麦国家 ART 夫妇 II 队列的建立得到了 Ebba Rosa Hansen 基金会的支持。资助者对数据收集、分析或呈现的结果没有影响。作者没有利益冲突。
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