Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Stanford Hospital and Clinics, Stanford, CA, USA.
Department of Urology, Stanford University School of Medicine, Stanford, CA, USA.
Hum Reprod. 2019 May 1;34(5):894-902. doi: 10.1093/humrep/dez018.
Is female infertility associated with higher risk of cancer?
Although absolute risks are low, infertility is associated with higher risk of cancer compared to a group of non-infertile women.
Infertile women are at higher risk of hormone-sensitive cancers. Information on risk of non-gynecologic cancers is rare and conflicting, and the effect of pregnancy on these risk associations is known for only a minority of cancer types.
STUDY DESIGN, SIZE, DURATION: Retrospective cohort analysis between 2003 and 2016 using an insurance claims database.
PARTICIPANTS/MATERIALS, SETTING, METHODS: In all, 64 345 infertile women identified by infertility diagnosis, testing or treatment were compared to 3 128 345 non-infertile patients seeking routine gynecologic care. Women with prior diagnosis of cancer or within 6 months of index event were excluded. Main outcomes were development of any malignancy and individual cancers as identified by ICD-9/ICD-10 codes. Results were adjusted for age at index date, index year, nulliparity, race, smoking, obesity, number of visits per year and highest level of education.
Infertile women had an overall higher risk of developing cancer compared to non-infertile women (2.0 versus 1.7%, adjusted hazard ratio (aHR) = 1.18; CI: 1.12-1.24). In addition, the risk of uterine cancer (0.10 versus 0.06%, aHR = 1.78; CI: 1.39-2.28), ovarian cancer (0.14 versus 0.09%, aHR 1.64; CI: 1.33-2.01), lung cancer (0.21 versus 0.21%, aHR = 1.38; CI: 1.01-1.88), thyroid cancer (0.21 versus 0.16%, aHR = 1.29; CI: 1.09-1.53), leukemia (0.10 versus 0.06%, aHR = 1.55; CI: 1.21-1.98) and liver and gallbladder cancer (0.05 versus 0.03%, aHR = 1.59; CI: 1.11-2.30) were higher in infertile women compared to non-infertile women. In a subgroup analysis of women in each cohort who became pregnant and had a delivery during enrollment, the risk of uterine and ovarian cancer were similar between infertile and non-infertile women. In a subgroup analysis excluding women with PCOS and endometriosis from both cohorts, the risk of uterine cancer was similar between infertile and non-infertile women.
LIMITATIONS, REASONS FOR CAUTION: Absolute risk of cancer was low, average follow up for each individual was limited, and average age at index date was limited. Insurance databases have known limitations.
Using claims-based data, we report that infertile women may have a higher risk of certain cancers in the years after infertility evaluation; continued follow up should be considered after reproductive goals are achieved.
STUDY FUNDING/COMPETING INTEREST(S): None.
女性不孕与癌症风险增加有关吗？
尽管绝对风险较低，但与非不孕女性相比，不孕与癌症风险增加相关。
不孕女性患激素敏感型癌症的风险较高。关于非妇科癌症风险的信息很少且存在冲突，并且仅对少数癌症类型的妊娠对这些风险关联的影响有所了解。
研究设计、大小和持续时间：2003 年至 2016 年期间使用保险索赔数据库进行的回顾性队列分析。
参与者/材料、设置、方法：共纳入 64345 名通过不孕诊断、检查或治疗确定的不孕女性，并与 3128345 名寻求常规妇科护理的非不孕患者进行比较。排除有癌症既往史或索引事件发生后 6 个月内的患者。主要结局为任何恶性肿瘤和通过 ICD-9/ICD-10 代码确定的个别癌症的发展。结果根据索引日期、索引年份、初产妇、种族、吸烟、肥胖、每年就诊次数和最高教育程度进行调整。
与非不孕女性相比，不孕女性总体上癌症发病风险更高（2.0%比 1.7%，调整后的危险比（aHR）=1.18；95%CI：1.12-1.24）。此外，子宫癌（0.10%比 0.06%，aHR=1.78；95%CI：1.39-2.28）、卵巢癌（0.14%比 0.09%，aHR=1.64；95%CI：1.33-2.01）、肺癌（0.21%比 0.21%，aHR=1.38；95%CI：1.01-1.88）、甲状腺癌（0.21%比 0.16%，aHR=1.29；95%CI：1.09-1.53）、白血病（0.10%比 0.06%，aHR=1.55；95%CI：1.21-1.98）和肝癌和胆囊癌（0.05%比 0.03%，aHR=1.59；95%CI：1.11-2.30）的发病风险更高。在每个队列中对怀孕并在入组期间分娩的女性进行亚组分析，不孕和非不孕女性的子宫癌和卵巢癌风险相似。在排除两个队列中多囊卵巢综合征和子宫内膜异位症女性后进行的亚组分析中，不孕和非不孕女性的子宫癌风险相似。
局限性、谨慎的原因：癌症的绝对风险较低，每位患者的平均随访时间有限，索引日期的平均年龄有限。保险数据库有其已知的局限性。
使用基于索赔的数据，我们报告说，不孕女性在不孕评估后数年可能有更高的某些癌症风险；在实现生殖目标后应考虑持续随访。
研究资金/利益冲突：无。
