Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.
Department of Urology, Stanford University, Palo Alto, CA, USA.
Hum Reprod. 2019 Nov 1;34(11):2266-2273. doi: 10.1093/humrep/dez189.
What is the risk of death among men with oligospermia, unspecified male factor and azoospermia in the years following fertility treatment?
No significantly elevated risk was observed among men with oligospermia and unspecified male factor, while an increased risk was found among men with azoospermia.
Previous studies have shown associations between male factor infertility and risk of death, but these studies have relied on internal reference groups and the risk of death according to type of male infertility is not well characterized.
STUDY DESIGN, SIZE, DURATION: In this prospective record-linkage cohort study, we identified men who had undergone medically assisted reproduction (MAR) between 1994 and 2015. Data was linked to the Danish causes of death register and sociodemographic registers through personal identification numbers assigned to all Danish citizens at birth.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Men that had undergone MAR in Denmark (MAR Cohort; n = 64 563) were identified from the Danish IVF register, which includes data on whether infertility was due to male factor. For each man in the MAR cohort, five age-matched men who became fathers without fertility treatment were selected from the general population (non-MAR fathers; n = 322 108). Men that could not adequately be tracked in the Danish CPR register (n = 1259) and those that were censored prior to study entry (n = 993) were excluded, leaving a final population of 384 419 men. Risk of death was calculated by Cox regression analysis with age as an underlying timeline and adjustments for educational attainment, civil status and year of study entry. The risk of death was compared among men with and without male factor infertility identified from the IVF register (internal comparisons) as well as to the non-MAR fathers (external comparison).
The risk of death between the MAR cohort (all men, regardless of infertility) and the non-MAR fathers was comparable [hazard ratio (HR), 1.07; 95% CI, 0.98-1.15]. When the MAR cohort was limited to infertile men, these men were at increased risk of death [HR, 1.27; 95% CI, 1.12-1.44]. However, when stratified by type of male factor infertility, men with azoospermia had the highest risk of death, which persisted when in both the internal [HR, 2.30; 95% CI, 1.54-3.41] and external comparison [HR, 3.32; 95% CI, 2.02-5.40]. No significantly elevated risk of death was observed among men with oligospermia [HR, 1.14; 95% CI, 0.87-1.50] and unspecified male factor [HR, 1.10; 95% CI, 0.75-1.61] compared with the non-MAR fathers. The same trends were observed for the internal comparison.
LIMITATIONS, REASONS FOR CAUTION: Duration of the follow-up was limited and there is limited generalizability to infertile men who do not seek fertility treatment.
Using national health registers, we found an increased risk of death among azoospermic men while no increased risk was found among men with other types of infertility. For the azoospermic men, further insight into causal pathways is needed to identify options for monitoring and prevention.
STUDY FUNDING/COMPETING INTEREST(S): This study is part of the ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS. C.G.'s research stay at Stanford was funded by grants from the University of Copenhagen, Kong Christian den Tiendes Fond, Torben og Alice Frimodt Fond and Julie Von Müllen Fond. M.E. is an advisor for Sandstone and Dadi. All other authors declare no conflict of interests.
Not relevant.
在接受生育治疗后的几年中，不明原因男性因素、少精子症和无精子症男性的死亡率是多少？
未发现不明原因男性因素和少精子症男性的死亡风险显著增加，而无精子症男性的死亡风险增加。
先前的研究表明男性因素不育与死亡风险之间存在关联，但这些研究依赖于内部参考组，并且根据男性不育症的类型，死亡风险的特征描述并不完善。
研究设计、规模、持续时间：在这项前瞻性记录链接队列研究中，我们确定了 1994 年至 2015 年间接受过医学辅助生殖（MAR）的男性。通过个人身份号码将数据与丹麦死因登记处和社会人口登记处相关联，该号码分配给所有丹麦公民出生时。
参与者/材料、设置、方法：从丹麦 IVF 登记处确定了丹麦接受 MAR 的男性（MAR 队列；n=64563），该登记处包含不育是否归因于男性因素的信息。对于 MAR 队列中的每一位男性，从一般人群中选择了 5 位年龄匹配的、无需生育治疗而成为父亲的男性（非 MAR 父亲；n=322108）。那些在丹麦 CPR 登记处无法充分跟踪（n=1259）和那些在研究入组前被屏蔽（n=993）的人被排除在外，最终留下了 384419 名男性。通过 Cox 回归分析计算死亡风险，年龄作为基础时间线，并调整教育程度、婚姻状况和研究入组年份。通过内部比较（从 IVF 登记处确定的男性因素不育男性与非 MAR 父亲）和外部比较（与非 MAR 父亲）比较男性因素不育男性和非 MAR 父亲的死亡风险。
MAR 队列（所有男性，无论不育与否）与非 MAR 父亲之间的死亡风险相当[风险比（HR），1.07；95%置信区间（CI），0.98-1.15]。当将 MAR 队列限制为不育男性时，这些男性的死亡风险增加[HR，1.27；95% CI，1.12-1.44]。然而，当按男性因素不育症的类型分层时，无精子症男性的死亡风险最高，这种风险在内部[HR，2.30；95% CI，1.54-3.41]和外部比较[HR，3.32；95% CI，2.02-5.40]中仍然存在。与非 MAR 父亲相比，少精子症和不明原因男性因素不育症男性的死亡风险无显著升高[HR，1.14；95% CI，0.87-1.50]和[HR，1.10；95% CI，0.75-1.61]。对于内部比较，也观察到了同样的趋势。
局限性、谨慎的原因：随访时间有限，并且对于不寻求生育治疗的不育男性的普遍性有限。
使用国家健康登记处，我们发现无精子症男性的死亡风险增加，而其他类型不育症男性的死亡风险没有增加。对于无精子症男性，需要进一步了解因果途径，以确定监测和预防的选择。
研究资助/利益冲突：本研究是 ReproUnion 合作研究的一部分，由欧盟、Interreg V ÖKS 共同资助。C.G 在斯坦福的研究停留由哥本哈根大学、Kong Christian den Tiendes 基金会、Torben og Alice Frimodt 基金会和 Julie Von Müllen 基金会资助。M.E. 是 Sandstone 和 Dadi 的顾问。所有其他作者均声明无利益冲突。
不适用。
