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Effect of paternal age on outcomes in assisted reproductive technology cycles: systematic review and meta-analysis 父亲年龄对辅助生殖技术周期结果的影响:系统回顾和荟萃分析
Pub Date : 2020-10-01 DOI: 10.1016/j.xfnr.2020.04.001
Guy Morris M.B.Ch.B. (Honours), M.R.C.O.G. , Dimitrios Mavrelos M.D., M.R.C.O.G. , Efstathios Theodorou M.R.C.O.G. , Mia Campbell-Forde B.Sc., M.Sc. , David Cansfield B.Sc. (Hons), M.Res. , Ephia Yasmin M.D., M.R.C.O.G. , Philippa Sangster M.Sc., F.R.C.S. (Urol) , Wael Saab M.D., M.R.C.O.G. , Paul Serhal F.R.C.O.G. , Srividya Seshadri M.D., M.Sc., M.R.C.O.G.

Objective

To investigate whether paternal age exerts an independent effect on the clinical outcomes of assisted reproductive technology (ART) cycles.

Evidence Review

Observational studies were identified through a systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and National Health Service evidence. Data for women aged ≤39 years were extracted and analyzed. We included all studies, both autologous and donor oocyte, into separate analyses of the effect of paternal age on ART outcome. We excluded studies in azoospermic men, women aged ≥40 years, ART including preimplantation genetic testing, and involving donor sperm. The included studies scored well on the Newcastle-Ottawa Quality Assessment Scale for observational studies. The primary outcome was live birth rate and secondary outcome measures were clinical pregnancy rate and miscarriage rate. When pooling data, the random-effects model was used to counter the effect of heterogeneity in the studies.

Result(s)

Live birth rate was reported in three autologous oocyte studies (2,926 cycles) and five donor oocyte studies (7,648 cycles). Live birth rate was found to be increased significantly when male age was <40 years in autologous oocyte studies but no difference in live birth rate was found in donor oocyte studies. Clinical pregnancy rates were found to be statistically higher when the paternal age was under 40 years in autologous oocyte studies, however, there was no difference in clinical pregnancy in the same age category when donor oocyte studies were analyzed. Miscarriage rate was reported in two autologous oocyte studies (970 cycles) and four donor oocyte studies (3,741 cycles). Miscarriage was found to be more likely with male age >40 years in autologous studies. In donor oocyte studies, the miscarriage rate was not increased when male age was >50 years. All of the autologous oocyte studies reported a statistically significant association between male age and female age.

Conclusion(s)

The findings of this review and meta-analysis, based on the donor oocyte model, suggest that advanced paternal age does not exert an independent effect on the outcome of ART cycles. Miscarriage rates do not appear to be increased even for men >50 years of age after treatment with donor oocytes. The meta-analysis of autologous oocyte studies suggests that increasing male age may have a deleterious effect on the outcome of ART, however, this may be confounded by the strong association with increasing maternal age.

目的探讨父亲年龄是否对辅助生殖技术(ART)周期的临床结果有独立影响。证据回顾:观察性研究是通过MEDLINE、EMBASE、Cochrane中央对照试验登记和国家卫生服务证据的系统检索确定的。提取年龄≤39岁女性的数据并进行分析。我们纳入了所有研究,包括自体和供体卵母细胞,分别分析父亲年龄对ART结果的影响。我们排除了无精子男性、年龄≥40岁女性、包括植入前基因检测的ART和涉及供体精子的研究。纳入的研究在观察性研究的纽卡斯尔-渥太华质量评估量表中得分很高。主要结局指标为活产率,次要结局指标为临床妊娠率和流产率。结果在3个自体卵母细胞研究(2,926个周期)和5个供体卵母细胞研究(7,648个周期)中报告了活产率。自体卵母细胞研究发现,当男性年龄为40岁时,活产率显著增加,而在供体卵母细胞研究中,活产率无差异。在自体卵母细胞研究中,发现父亲年龄在40岁以下的临床妊娠率有统计学意义较高,而在供体卵母细胞研究中,相同年龄的临床妊娠率无统计学差异。2例自体卵母细胞研究(970个周期)和4例供体卵母细胞研究(3741个周期)报告了流产率。在自体研究中发现,40岁的男性更容易流产。在供体卵母细胞研究中,当男性年龄为50岁时,流产率没有增加。所有的自体卵母细胞研究都报道了男性年龄和女性年龄之间具有统计学意义的相关性。结论:本综述和基于供体卵母细胞模型的荟萃分析的结果表明,父亲年龄的增加对ART周期的结果没有独立的影响。即使是50岁的男性,在接受供体卵母细胞治疗后,流产率似乎也没有增加。自体卵母细胞研究的荟萃分析表明,男性年龄的增加可能对抗逆转录病毒治疗的结果产生有害影响,然而,这可能与母亲年龄增加的强烈关联相混淆。
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