STUDY QUESTION Among couples with infertility and normal total sperm count and motility, can sperm morphology be used as a biomarker to identify couples who benefit more from ICSI over conventional IVF (c-IVF) on fertility outcomes? SUMMARY ANSWER Based on this secondary analysis of a large randomized clinical trial (RCT), sperm morphology has limited value as a biomarker to identify couples who benefit more from ICSI over c-IVF on live birth, ongoing pregnancy, clinical pregnancy or total fertilization failure. WHAT IS KNOWN ALREADY Our recent RCT showed that ICSI did not result in higher live birth rates in couples with normal total sperm count and motility. It is unclear whether sperm morphology can be used as a biomarker to identify couples who benefit more from ICSI over c-IVF in this population. STUDY DESIGN, SIZE, DURATION This was a secondary analysis of an open-label, multi-centre, RCT comparing ICSI versus c-IVF in 1064 couples with infertility and normal total sperm count and motility. In this secondary study, we evaluated the effectiveness of ICSI over c-IVF in relation to sperm morphology. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples were eligible if they had ≤2 previous IVF/ICSI attempts, and the male partner had normal total sperm count and motility according to the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Sperm morphology was measured from samples obtained during the first consultation and data for sperm morphology were available in partners of all participants in this trial. The outcomes of interest were live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure. We first conducted a logistic regression analysis with an interaction term (sperm morphology as a continuous variable by treatment (ICSI versus c-IVF)) on the four outcomes. We also used restricted cubic spline analysis to evaluate non-linear interaction and plotted the treatment effects of ICSI over c-IVF at different sperm morphology levels and the predicted probability of these outcomes in both ICSI and c-IVF groups. MAIN RESULTS AND THE ROLE OF CHANCE The median proportion of sperm with normal morphology in both groups was 3% (Interquartile range 1–6%). Live birth rates were (184/532) 34.6% for ICSI versus (166/532) 31.2% for c-IVF. No significant interaction was found between sperm morphology and treatment effect of ICSI versus c-IVF on the rates of live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure (P = 0.181, 0.153, 0.168, and 0.788 respectively). In the analyses using restricted cubic splines, no evidence of interaction between sperm morphology and the treatment effect was found. Interaction figures showed that the treatment effect of ICSI over c-IVF at different sperm morphology levels was fluctuating around no effect line, and the predicted outcomes for the two groups were mostly overlapping at different sperm morphology levels. LIMITATIONS AND REASONS FOR CAUTION This secondary analysis may be underpowered to detect a difference in treatment effects at different sperm morphology levels due to relatively small number of events at some sperm morphology levels. Moreover, sperm morphology assessment was performed during the first consultation, rather than on the day of randomization. WIDER IMPLICATIONS OF THE FINDINGS In couples with infertility and normal total sperm count and motility, sperm morphology has a limited role as a biomarker to identify couples who benefit more from ICSI over c-IVF on fertility outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by My Duc Hospital, Ho Chi Minh City, Vietnam. RW was supported by an NHMRC EL Investigator Grant (GNT2009767). LNV has received speaker and conference fees from Merck, grant, speaker, conference fees from Merck Sharpe and Dohme, and speaker, conference, and scientific board fees from Ferring. TMH has received speaker fees from Merck, Merck Sharp Dohme, and Ferring. BWM reports consultancy, travel support and research funding from Merck and consultancy for Organon and Norgine. BWM holds stock from ObsEva. TRIAL REGISTRATION NUMBER NCT03428919

中文翻译：

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卵胞浆内单精子注射与常规体外受精对精子总数和活力正常的不孕夫妇的比较：精子形态重要吗？


研究问题 在不孕症且总精子数量和活力正常的夫妇中，精子形态是否可以用作生物标志物来识别从ICSI中受益比传统IVF （c-IVF） 在生育结果方面受益更多的夫妇？总结答案 根据一项大型随机临床试验 （RCT） 的二次分析，精子形态作为生物标志物的价值有限，无法识别在活产、持续妊娠、临床妊娠或完全受精失败方面从 ICSI 中受益超过 c-IVF 的夫妇。已经知道的 我们最近的 RCT 表明，ICSI 不会导致总精子数量和活力正常的夫妇的活产率更高。目前尚不清楚精子形态是否可以用作生物标志物来识别在该人群中从 ICSI 中受益更多而不是 c-IVF 的夫妇。研究设计、规模、持续时间 这是一项开放标签、多中心、随机对照试验的二次分析，在 1064 对不孕症和总精子数量和活力正常的夫妇中比较 ICSI 与 c-IVF。在这项二次研究中，我们评估了 ICSI 优于 c-IVF 对精子形态的有效性。参与者/材料、设置、方法 根据 WHO 第五版人类精液检查和处理实验室手册，如果夫妇之前有 ≤2 次 IVF/ICSI 尝试，并且男性伴侣的总精子数量和活力正常，则他们符合条件。从第一次咨询期间获得的样本中测量精子形态，并且精子形态数据可在该试验的所有参与者的伴侣中获得。感兴趣的结局是活产、持续妊娠、临床妊娠和完全受精失败。 我们首先对四个结局进行了交互项 （精子形态作为治疗的连续变量 （ICSI 与 c-IVF） ） 的 logistic 回归分析。我们还使用限制性三次样条分析来评估非线性相互作用，并绘制了 ICSI 对不同精子形态水平下 c-IVF 的治疗效果以及 ICSI 和 c-IVF 组中这些结果的预测概率。主要结果和机会的作用 两组中形态正常的精子的中位比例为 3%（四分位距 1-6%）。ICSI 的活产率为 （184/532） 34.6%，而 c-IVF 的活产率为 （166/532） 31.2%。未发现精子形态与 ICSI 与 c-IVF 的治疗效果对活产率、持续妊娠率、临床妊娠率和总受精失败率的显着交互作用 （P = 0.181 、 0.153 、 0.168 和 0.788）。在使用限制性三次样条的分析中，没有发现精子形态与治疗效果之间相互作用的证据。交互图显示，ICSI 优于 c-IVF 在不同精子形态水平上的治疗效果在无影响线附近波动，两组预测结果在不同精子形态水平上大多重叠。限制和谨慎的原因由于某些精子形态水平的事件数量相对较少，这种二次分析可能不足以检测不同精子形态水平的治疗效果差异。此外，精子形态学评估是在第一次咨询期间进行的，而不是在随机分组当天进行的。 研究结果的更广泛意义 在不孕症且总精子数量和活力正常的夫妇中，精子形态作为生物标志物的作用有限，无法识别从 ICSI 中受益比 c-IVF 对生育结果更有利的夫妇。研究资金/竞争利益 本研究由越南胡志明市 My Duc 医院资助。RW 得到了 NHMRC EL 研究者资助 （GNT2009767） 的支持。LNV 已收到 Merck 的演讲和会议费用、Merck Sharpe 和 Dohme 的赠款、演讲者、会议费用，以及 Ferring 的演讲者、会议和科学委员会费用。TMH 已收到 Merck、Merck Sharp Dohme 和 Ferring 的演讲费。BWM 报告了默克的咨询、差旅支持和研究资金，以及 Organon 和 Norgine 的咨询。BWM 持有 ObsEva 的股票。试验注册号 NCT03428919