STUDY QUESTION Does advanced male partner’s age impact live birth rates (LBRs) in IVF treatment when female partner’s age is factored in? SUMMARY ANSWER In fresh IVF cycles LBRs decline with male partner’s age ≥40 years when the female partner is aged 35–39 years, irrespective of the presence or absence of male factor; but not when the female partner is <35 years or ≥40 years of age; this decline is not observed in ICSI cycles. WHAT IS KNOWN ALREADY Advanced paternal age is associated with declining sperm parameters, impaired embryo development, compromised pregnancy outcomes, and abnormalities in the offspring in IVF/ICSI cycles. However, data on the interaction between maternal and paternal age on IVF outcomes are very limited and inconsistent. No significant effect of male partner’s age on pregnancy outcomes has been noted in donor oocyte cycles. STUDY DESIGN, SIZE, DURATION Retrospective analysis of all eligible autologous IVF/ICSI cycles with oocyte retrieval and intended fresh embryo transfer (ET) from the UK’s national anonymized registry, published online by the Human Fertilisation and Embryology Authority (HFEA). There were 59 951 cycles that qualified the inclusion criteria in the study period: 1 January 2017 to 31 December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples underwent IVF (n = 27 226) or ICSI (n = 32 725) treatment with partner’s sperm followed by fresh ET due to unexplained (n = 31 846), tubal (n = 6605), or male infertility (n = 22 905). Treatment cycles with endometriosis (n = 5563), ovulatory disorders (n = 9970), female partner aged >44 years (n = 636), and PGT (n = 280) were excluded. Women were stratified by age in the following groups: <35, 35–39, 40–42, and 43–44 years; male partner’s age as <35 (reference group), 35–37, 38–39, 40–42, 43–44, 45–50, 51–55, 55–60, and >55 years as presented by the HFEA. Some age-groups were merged in the analysis to increase the population size. Chi-square test was used to compare binominal data; and multiple logistic regression to find any association between male and female age-groups on live birth adjusting for other confounders that had a significant effect on this outcome. MAIN RESULTS AND THE ROLE OF CHANCE LBRs per oocyte retrieval as well as per ET were no different across the male partners’ age-groups when the female partners were aged <35 years or in 40- to 44-year age-group, whether male-factor infertility was included or excluded and whether it was IVF or ICSI cycle. However, when IVF was the method of insemination in the female partner’s age-group of 35–39 years, LBRs per oocyte retrieval dropped significantly from 27.0% in the male age-group of <35 years (reference group) to 22.9% (P = 0.002), 22.0% (P = 0.006), and 18.8% (P = 0.004) in 40–44, 45–50, and >50 years age-group, respectively in population that included male-factor infertility. Likewise, LBR per retrieval declined from 27.6% in 35 years age-group to 23.5% (P = 0.002) and 22.2% (P = 002) in 40–44 years and older groups, respectively in cycles without male infertility. However, there was no impact of male age on LBR in any female partner’s age-group when ICSI was performed in either the presence or the absence of male infertility. A similar decline in the LBR per retrieval and per ET was observed in female age-group of 35–39 years in the analyses with IVF and ICSI cycles combined. The inference remained unchanged when only the first treatment cycle was included (per patient analysis) or when single blastocyst transfer cycles were analysed, eliminating the impact of the number and stage of embryo transferred. After adjusting for confounders including male age, female age, number of previous treatment cycles, previous live birth, insemination method (IVF or ICSI), number of embryos transferred, and day (stage) of ET, male partner’s age remained significantly associated with LBR in the female age-group of 35–39 years, but not when women were in <35 years or 40- to 44-year age-group, in population including as well as excluding male infertility. Miscarriage rates per single ET trended to rise (non-significantly) in IVF as well as ICSI cycle only when men were over 55 years and female partners aged <40 years, particularly when male infertility was excluded. LIMITATIONS, REASONS FOR CAUTION Information on ovarian reserve and stimulation protocols was not available. This probably would have had little impact, given the large size of the population studied. The ages of female and male partners were given in groups necessitating taking them as ordinal variable in the regression analysis. Cumulative LBRs could not be determined as the information on subsequent frozen-thawed ET cycles could not be traced and the severity or cause of abnormal semen parameters were not present in the HFEA database. Some age-groups with small number of patients were merged to obtain a reliable result. WIDER IMPLICATIONS OF THE FINDINGS This is the largest clinical data to support the laboratory evidence of the ability of oocytes from young women to reverse the age-related deterioration of sperm quality. As the ageing oocytes lose this reparatory mechanism, the ageing sperm exert a detrimental effect on the LBR. The message of this study is important in counselling of patients and planning out treatment. Further research on interaction between male and female age will increase our understanding of this matter and help to establish whether ICSI procedure is more appropriate for older male partners even when there is no apparent semen abnormality. STUDY FUNDING/COMPETING INTEREST(S) No funding was required. There is no competing interest. TRIAL REGISTRATION NUMBER N/A (retrospective analysis).

中文翻译：

---

活产率受男性和女性伴侣年龄之间相互作用的影响：分析 59 951 个新鲜 IVF/ICSI 周期，有和没有男性不育症


研究问题：当考虑到女性伴侣的年龄时，高级男性伴侣的年龄是否会影响 IVF 治疗中的活产率 （LBR）？总结答案 在新的体外受精周期中，LBR 会随着男性伴侣的年龄 ≥40 岁而下降，而女性伴侣的年龄为 35-39 岁，无论是否存在男性因素;但当女性伴侣 <35 岁或 ≥40 岁时不行;在 ICSI 周期中未观察到这种下降。已知的 高龄父亲与精子参数下降、胚胎发育受损、妊娠结果受损以及 IVF/ICSI 周期中后代异常有关。然而，关于母亲和父亲年龄对 IVF 结局的相互作用的数据非常有限且不一致。在供体卵母细胞周期中，未发现男性伴侣的年龄对妊娠结局有显著影响。研究设计、规模、持续时间 回顾性分析所有符合条件的自体 IVF/ICSI 周期，包括取卵和预期的新鲜胚胎移植 （ET），来自英国国家匿名登记处，由人类受精和胚胎学管理局 （HFEA） 在线发布。在研究期间（2017 年 1 月 1 日至 2018 年 12 月 31 日），有 59 951 个周期符合纳入标准。参与者/材料、设置、方法 夫妇接受了用伴侣精子进行的 IVF （n = 27 226） 或 ICSI （n = 32 725） 治疗，然后由于原因不明 （n = 31 846）、输卵管 （n = 6605） 或男性不育症 （n = 22 905） 进行了新鲜 ET。子宫内膜异位症 （n = 5563） 、排卵障碍 （n = 9970） 、年龄 >44 岁 （n = 636） 和 PGT （n = 280） 的治疗周期被排除在外。 女性按年龄分为以下组：<35、35-39、40-42 和 43-44 岁;男性伴侣的年龄为 <35（参考组）、35-37、38-39、40-42、43-44、45-50、51-55、55-60 和 >55 岁，由 HFEA 提供。在分析中合并了一些年龄组以增加种群规模。卡方检验比较双名数据;和多元 logistic 回归，以发现男性和女性年龄组与活产率之间的任何关联，并调整对该结局有显着影响的其他混杂因素。主要结果和每次取卵的机会 LBRs 的作用在男性伴侣的年龄组中没有差异 <35 岁或 40 至 44 岁年龄组，是否包括或排除男性因素不孕症，无论是 IVF 还是 ICSI 周期。然而，当 IVF 是女性伴侣 35-39 岁年龄组的授精方法时，每次取卵的 LBR 从 <35 岁男性年龄组（参考组）的 27.0% 显着下降到 22.9% （P = 0.002）、22.0% （P = 0.006） 和 18.8% （P = 0.004） 分别在 40-44 岁、45-50 岁和 >50 岁年龄组中，在包括男性因素不孕症的人群中。同样，在没有男性不育症的周期中，每次检索的 LBR 从 35 岁年龄组的 27.6% 分别下降到 40-44 岁及以上组的 23.5% （P = 0.002） 和 22.2% （P = 002）。然而，在存在或不存在男性不育症的情况下进行 ICSI 时，男性年龄对任何女性伴侣年龄组的 LBR 都没有影响。在 IVF 和 ICSI 周期相结合的分析中，在 35-39 岁的女性年龄组中观察到每次取卵和每次 ET 的 LBR 也有类似的下降。 当仅包括第一个治疗周期（每个患者分析）或分析单个囊胚移植周期时，推断保持不变，从而消除了胚胎移植数量和阶段的影响。在调整了包括男性年龄、女性年龄、既往治疗周期数、既往活产、授精方法（IVF 或 ICSI）、移植胚胎数量和 ET 的天数（阶段）在内的混杂因素后，男性伴侣的年龄与 LBR 在 35-39 岁的女性年龄组中仍然显著相关，但当女性处于 <35 岁或 40 至 44 岁年龄组时则不然， 在人群中包括和排除男性不育症。只有当男性超过 55 岁和女性伴侣年龄 <40 岁时，每个单次 ET 的流产率在 IVF 和 ICSI 周期中呈上升（不显着）的趋势，特别是当排除男性不育症时。局限性，谨慎的原因 没有关于卵巢储备和刺激方案的信息。考虑到所研究的种群规模很大，这可能影响不大。女性和男性伴侣的年龄被分组给出，因此有必要在回归分析中将他们作为顺序变量。由于无法追踪后续冻融 ET 周期的信息，并且 HFEA 数据库中不存在异常精液参数的严重程度或原因，因此无法确定累积 LBR。合并一些患者人数较少的年龄组以获得可靠的结果。研究结果的更广泛意义 这是支持年轻女性卵母细胞能够逆转与年龄相关的精子质量恶化的实验室证据的最大临床数据。 随着衰老的卵母细胞失去这种修复机制，衰老的精子对 LBR 产生不利影响。这项研究的信息对于患者咨询和规划治疗很重要。对男性和女性年龄之间相互作用的进一步研究将增加我们对这个问题的理解，并有助于确定即使没有明显的精液异常，ICSI 程序是否更适合老年男性伴侣。研究资金/竞争利益 不需要资金。没有竞争利益。试验注册号 N/A（回顾性分析）。