Child Population and Translational Health Research, The Children's Hospital at Westmead Clinical School, The University of Sydney, NSW, Australia.
Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Lancet Child Adolesc Health. 2018 Oct;2(10):736-743. doi: 10.1016/S2352-4642(18)30254-2. Epub 2018 Aug 30.
The male genital anomalies hypospadias and undescended testes have been linked to adult male reproductive disorders, testicular cancer, and decreased fertility. Few population-based studies have evaluated their effects on adult fertility outcomes and, in the case of undescended testes, the importance of early corrective surgery (orchidopexy).
We did a population-based cohort study of all liveborn boys in Western Australia in 1970-99, and followed them up until 2016 via data linkage to registries for hospital admissions, congenital anomalies, cancer, and assisted reproductive technologies (ART). Study factors were hypospadias or undescended testes, and study outcomes were testicular cancer, paternity, and use of ART for male infertility. Cox regression was used to calculate hazard ratios (HRs) for the associations between genital anomalies and testicular cancer or paternity, and log-binomial regression was used to calculate relative risks (RRs) for the associations between genital anomalies and use of ART.
The cohort comprised 350 835 boys, of whom 2484 (0·7%) had been diagnosed with hypospadias and 7499 (2·1%) with undescended testes. There were 505 (0·1%) cases of testicular cancer, 109 471 (31·2%) men had fathered children, and 2682 (0·8%) had undergone fertility treatment with ART. Undescended testes was associated with a more than two times increase in risk of testicular cancer (HR 2·43, 95% CI 1·65-3·58) and hypospadias with an almost 40% increase (1·37, 0·51-3·67), although this increase was not significant. Both hypospadias and undescended testes were associated with a 21% reduction in paternity (adjusted HR 0·79 [95% CI 0·71-0·89] for hypospadias and 0·79 [0·74-0·85] for undescended testes). Undescended testes was associated with a two times increase in use of ART (adjusted RR 2·26, 95% CI 1·58-3·25). For every 6 months' delay in orchidopexy, there was a 6% increase in risk of testicular cancer (HR 1·06, 95% CI 1·03-1·08), a 5% increase in risk of future use of ART (1·05, 1·03-1·08), and a 1% reduction in paternity (RR 0·99, 95% CI 0·98-0·99).
Undescended testes is associated with an increased risk of testicular cancer and male infertility, and decreased paternity. We provide new evidence to support current guidelines for orchidopexy before age 18 months to decrease the risk of future testicular cancer and infertility.
National Health and Medical Research Council and Sydney Medical School Foundation.
男性生殖器异常，如尿道下裂和隐睾，与成年男性生殖障碍、睾丸癌和生育能力下降有关。很少有基于人群的研究评估了它们对成年生育结果的影响，而且对于隐睾，早期矫正手术（睾丸固定术）的重要性也尚未可知。
我们对 1970 年至 1999 年西澳大利亚州所有活产男婴进行了基于人群的队列研究，并通过数据链接对他们进行了随访，直至 2016 年，这些数据链接到了医院入院、先天性异常、癌症和辅助生殖技术（ART）的登记处。研究因素为尿道下裂或隐睾，研究结局为睾丸癌、父亲身份和男性不育症的 ART 治疗。使用 Cox 回归计算生殖器异常与睾丸癌或父亲身份之间的关联的风险比（HR），使用对数二项式回归计算生殖器异常与使用 ART 治疗之间的关联的相对风险（RR）。
该队列包括 350835 名男婴，其中 2484 名（0.7%）被诊断为尿道下裂，7499 名（2.1%）为隐睾。有 505 例（0.1%）睾丸癌，109471 名（31.2%）男性成为了父亲，2682 名（0.8%）接受了 ART 生育治疗。隐睾与睾丸癌风险增加两倍以上相关（HR 2.43，95%CI 1.65-3.58），尿道下裂与睾丸癌风险增加近 40%相关（1.37，0.51-3.67），但这一增加并不显著。尿道下裂和隐睾均与父亲身份降低 21%相关（尿道下裂的校正 HR 0.79 [95%CI 0.71-0.89]，隐睾的校正 HR 0.79 [0.74-0.85]）。隐睾与 ART 使用率增加两倍相关（校正 RR 2.26，95%CI 1.58-3.25）。睾丸固定术每延迟 6 个月，睾丸癌风险增加 6%（HR 1.06，95%CI 1.03-1.08），未来使用 ART 的风险增加 5%（1.05，1.03-1.08），父亲身份降低 1%（RR 0.99，95%CI 0.98-0.99）。
隐睾与睾丸癌和男性不育风险增加以及父亲身份降低有关。我们提供了新的证据，支持目前在 18 个月前进行睾丸固定术的指南，以降低未来睾丸癌和不育的风险。
澳大利亚国家卫生和医学研究委员会和悉尼医学院基金会。
