EPRD, Department of Obstetrics and Gynecology, Monash University, Melbourne, VIC 3168, Australia.
Monash IVF, Melbourne, VIC 3168, Australia.
Hum Reprod. 2019 Dec 1;34(12):2523-2532. doi: 10.1093/humrep/dez223.
Is male age associated with the clinical outcomes of IVF/ICSI cycles for idiopathic infertility after adjustment for female age?
Male ageing is negatively associated with clinical IVF/ICSI outcomes in couples with idiopathic infertility independent of female age.
The effect of male age on the outcomes of infertility treatments is controversial and poorly explored. In contrast, fertility is known to decline significantly with female age beyond the mid-30s, and reduced oocyte quality plays an important role. The negative effect of male age on sperm quality is largely associated with an increasing susceptibility to sperm DNA damage. Although increasing maternal age has been linked with poorer oocyte quality, studies on the effect of male age have disregarded the need to control for female age making it difficult to define clearly the role of male age in infertile couples.
STUDY DESIGN, SIZE, DURATION: This retrospective cohort study analysed 2425 cycles of couples with idiopathic infertility selected from a total of 24 411 IVF/ICSI cycles performed at Monash IVF in Australia between 1992 and 2017. The primary outcome was live birth and secondary outcomes were clinical pregnancy and miscarriage.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples with primary/secondary infertility who underwent IVF/ICSI cycles with male partners classified as normozoospermic were selected (inclusion criteria). Couples in which the female partner had endometriosis, tubal factors, polycystic ovarian syndrome, ovarian hyperstimulation syndrome, poor responders (≤3 mature oocytes retrieved) and couples with more than 15 cumulus oocyte complexes retrieved or who used cryopreserved gametes were excluded. Binary logistic multilevel modelling was used to identify the effect of male age and female age on clinical outcomes after controlling for confounding factors. Male age and female age were examined as continuous and categorical (male age: <40, 40-44, 45-49, 50-54, ≥55; female age:<30, 30-34, 35-39, ≥40) predictors.
There was a negative effect of male age and female age on live birth as odds ratios (OR) with 95% CI for each additional year of age (OR-male age: 0.96 [0.94-0.98]; OR-female age: 0.90 [0.88-0.93] P < 0.001). Potential interactions with male age such as type of treatment (IVF/ICSI), embryo transfer day (Day 3/Day 5) and female age did not have significant associations with outcomes (P > 0.05). Secondary outcomes showed a significant reduction in the odds of clinical pregnancy (OR-male age: 0.97 [0.96-0.99]; OR-female age: 0.92 [0.89-0.94] P < 0.001) and an increase in the odds of miscarriage with older age: male age (OR: 1.05 [1.01-1.08]; P = 0.002); female age (OR: 1.11 [1.05-1.18]; P < 0.001). Worse outcomes were associated with more cycles (clinical pregnancy-OR: 0.96 [0.93-0.99] P = 0.03; live birth-OR: 0.96 [0.92-0.99] P = 0.023) while more inseminated oocytes were associated with better outcomes (clinical pregnancy-OR: 1.06 [1.03-1.06] P < 0.001; live birth-OR: 1.07 [1.04-1.11] P < 0.001). Analyses for age categories showed a gradual worsening of clinical outcomes with increasing male age, with a significantly worse live birth and clinical pregnancy outcomes in males aged older than 50 years compared to males younger than 40 years (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION: This study is limited to the information on confounding factors included. The study may also be limited in its generalizability to a wider population due the strict selection criteria. Age as a category could potentially result in residual confounding due to categorizing a continuous variable.
This study provides information for counselling of couples with idiopathic infertility.
STUDY FUNDING/COMPETING INTEREST(S): Funded by the Education Program in Reproduction and Development, Department of Obstetrics and Gynaecology, Monash University. None of the authors has any conflict of interest to report.
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在调整女性年龄后，男性年龄是否与特发性不孕的 IVF/ICSI 周期的临床结局相关？
男性年龄的增长与特发性不孕夫妇的 IVF/ICSI 临床结局呈负相关，而与女性年龄无关。
男性年龄对不孕治疗结局的影响存在争议，且研究不足。相比之下，女性年龄超过 30 多岁后生育能力显著下降，卵子质量下降是一个重要原因。男性年龄的增加与精子 DNA 损伤的易感性增加密切相关。尽管越来越多的母亲年龄与卵子质量较差有关，但关于男性年龄影响的研究忽略了控制女性年龄的必要性，因此难以明确男性年龄在不孕夫妇中的作用。
研究设计、规模、持续时间：本回顾性队列研究分析了 1992 年至 2017 年期间在澳大利亚莫纳什 IVF 进行的 2425 个特发性不孕夫妇的 IVF/ICSI 周期，这些夫妇的伴侣被归类为正常精子数量。排除了女性伴侣患有子宫内膜异位症、输卵管因素、多囊卵巢综合征、卵巢过度刺激综合征、反应不良（≤3 个成熟卵母细胞）以及取卵超过 15 个或使用冷冻保存配子的夫妇。采用二元逻辑多层模型，在控制混杂因素后，确定男性年龄和女性年龄对临床结局的影响。男性年龄和女性年龄作为连续和分类变量（男性年龄：<40、40-44、45-49、50-54、≥55；女性年龄：<30、30-34、35-39、≥40）进行评估。
男性年龄和女性年龄对活产的影响呈负相关，其优势比（OR）的 95%置信区间（OR-男性年龄：0.96 [0.94-0.98]；OR-女性年龄：0.90 [0.88-0.93]，P<0.001）。潜在的男性年龄与结局的交互作用，如治疗类型（IVF/ICSI）、胚胎移植日（第 3 天/第 5 天）和女性年龄，与结局没有显著关联（P>0.05）。次要结局显示临床妊娠的几率显著降低（OR-男性年龄：0.97 [0.96-0.99]；OR-女性年龄：0.92 [0.89-0.94]，P<0.001），而流产几率随着年龄的增加而增加：男性年龄（OR：1.05 [1.01-1.08]；P=0.002）；女性年龄（OR：1.11 [1.05-1.18]；P<0.001）。更多的周期与较差的结局相关（临床妊娠-OR：0.96 [0.93-0.99]，P=0.03；活产-OR：0.96 [0.92-0.99]，P=0.023），而更多的授精卵与更好的结局相关（临床妊娠-OR：1.06 [1.03-1.06]，P<0.001；活产-OR：1.07 [1.04-1.11]，P<0.001）。年龄分类分析显示，随着男性年龄的增加，临床结局逐渐恶化，与 40 岁以下的男性相比，年龄大于 50 岁的男性的活产和临床妊娠结局明显更差（P<0.05）。
局限性、谨慎原因：本研究仅限于纳入的混杂因素的信息。由于严格的选择标准，该研究也可能在其普遍性方面受到限制。年龄作为一个类别可能会由于对连续变量进行分类而导致残留混杂。
本研究为特发性不孕夫妇提供了咨询信息。
研究资金/利益冲突：由 Monash 大学妇产科生殖与发育教育计划资助。作者均无任何利益冲突。
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