McDowell Simon, Kroon Ben, Ford Emily, Hook Ysanne, Glujovsky Demián, Yazdani Anusch
Queensland Fertility Group Research Foundation, 55 Little Edward St, Level 2 Boundary Court, Spring Hill, Brisbane, Queensland, Australia, 4000.
Cochrane Database Syst Rev. 2014 Oct 28(10):CD010461. doi: 10.1002/14651858.CD010461.pub2.
Assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) bring together gametes outside of the body to enhance the probability of fertilisation and pregnancy. Advanced sperm selection techniques are increasingly being employed in ART, most commonly in cycles utilising ICSI. Advanced sperm selection techniques are thought to improve the chance that structurally intact and mature sperm with high DNA integrity are selected for fertilisation. Advanced sperm selection strategies include selection according to surface charge; sperm apoptosis; sperm birefringence; ability to bind to hyaluronic acid; and sperm morphology under ultra-high magnification. These techniques theoretically improve ART outcomes.
To evaluate the impact of advanced sperm selection techniques on ART outcomes.
Systematic search of electronic databases (Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Health Science Information Database (LILACS)), trials registers (ClinicalTrials.gov, Current Controlled Trials, World Health Organization International Clinical Trials Registry Platform), conference abstracts (Web of Knowledge) and grey literature (OpenGrey) for relevant randomised controlled trials. We handsearched the reference lists of included studies and similar reviews. The search was conducted in May 2014.
We included randomised controlled trials (RCTs) comparing an advanced sperm selection technique versus standard IVF or ICSI or versus another advanced sperm selection technique. We excluded studies of sperm selection using ultra-high magnification (intracytoplasmic morphologically selected sperm injection, or IMSI), as they are the subject of a separate Cochrane review. Quasi-randomised and pseudo-randomised trials were excluded. Our primary outcome measure was live birth rate per woman randomly assigned. Secondary outcome measures included clinical pregnancy per woman randomly assigned, miscarriage per clinical pregnancy and fetal abnormality per clinical pregnancy.
Two review authors independently assessed eligibility of studies and risk of bias, and performed data extraction. Disagreements were resolved by consultation with a third review author. Study investigators were consulted to resolve other queries that arose. Risk ratios (RRs) were calculated with 95% confidence intervals (CIs). We planned to combine studies using a fixed-effect model, if sufficient data were available. The quality of the evidence was evaluated using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methods.
Two RCTs were included in the review. Both evaluated sperm selection by hyaluronanic acid binding for ICSI, but only one reported live births. No studies were identified that were related to surface charge selection, sperm apoptosis or sperm birefringence.One RCT compared hyaluronanic acid binding versus conventional ICSI. Live birth was not reported. Evidence was insufficient to show whether there was a difference between groups in clinical pregnancy rates (RR 1.01, 95% CI 0.84 to 1.22, one RCT, 482 women). This evidence was deemed to be of low quality, mainly as the result of poor reporting of methods and findings. Miscarriage data were unclear, and fetal abnormality rates were not reported.The other RCT compared two different hyaluronanic acid binding techniques, SpermSlow and physiological intracytoplasmic sperm injection (PISCI). Evidence was insufficient to indicate whether there was a difference between groups in rates of live birth (RR 1.16, 95% CI 0.65 to 2.05, one RCT, 99 women), clinical pregnancy (RR 1.07, 95% CI 0.67 to 1.71, one RCT, 99 women) or miscarriage (RR 0.76, 95% CI 0.24 to 2.44, one RCT, 41 women). The evidence for these comparisons was deemed to be of low quality, as it was limited by imprecision and poor reporting of study methods. Fetal abnormality rates were not reported.
AUTHORS' CONCLUSIONS: Evidence was insufficient to allow review authors to determine whether sperm selected by hyaluronanic acid binding improve live birth or pregnancy outcomes in ART, and no clear data on adverse effects were available. Evidence was also insufficient to show whether there is a difference in efficacy between the hyaluronic acid binding methods SpermSlow and PICSI. No randomised evidence evaluating sperm selection by sperm apoptosis, sperm birefringence or surface charge was found.Further studies of suitable quality are required to evaluate whether any of these advanced sperm selection techniques can be recommended for use in clinical practice.
体外受精（IVF）和卵胞浆内单精子注射（ICSI）等辅助生殖技术（ART）在体外使配子结合，以提高受精和怀孕的概率。先进的精子筛选技术在ART中应用越来越广泛，最常见于使用ICSI的周期中。先进的精子筛选技术被认为可以提高选择结构完整、成熟且DNA完整性高的精子进行受精的机会。先进的精子筛选策略包括根据表面电荷进行筛选；精子凋亡；精子双折射；与透明质酸结合的能力；以及超高倍放大下的精子形态。从理论上讲，这些技术可改善ART的结局。
评估先进的精子筛选技术对ART结局的影响。
系统检索电子数据库（Cochrane月经紊乱与生育力低下小组专业注册库、Cochrane对照试验中央注册库（CENTRAL）、MEDLINE、EMBASE、PsycINFO、护理学与健康相关文献累积索引（CINAHL）、拉丁美洲和加勒比健康科学信息数据库（LILACS））、试验注册库（ClinicalTrials.gov、当前对照试验、世界卫生组织国际临床试验注册平台）、会议摘要（Web of Knowledge）和灰色文献（OpenGrey），以查找相关的随机对照试验。我们手工检索了纳入研究和类似综述的参考文献列表。检索于2014年5月进行。
我们纳入了比较先进的精子筛选技术与标准IVF或ICSI或与另一种先进的精子筛选技术的随机对照试验（RCT）。我们排除了使用超高倍放大进行精子筛选的研究（卵胞浆内形态学选择精子注射，即IMSI），因为它们是另一项Cochrane综述的主题。排除半随机和伪随机试验。我们的主要结局指标是随机分组的每位女性的活产率。次要结局指标包括随机分组的每位女性的临床妊娠率、每次临床妊娠的流产率和每次临床妊娠的胎儿异常率。
两位综述作者独立评估研究的纳入资格和偏倚风险，并进行数据提取。通过与第三位综述作者协商解决分歧。向研究调查人员咨询以解决出现的其他疑问。计算风险比（RR）及其95%置信区间（CI）。如果有足够的数据，我们计划使用固定效应模型合并研究。使用推荐分级、评估、制定与评价（GRADE）方法评估证据质量。
本综述纳入了两项RCT。两者均评估了ICSI中通过透明质酸结合进行的精子筛选，但只有一项报告了活产情况。未发现与表面电荷筛选、精子凋亡或精子双折射相关的研究。一项RCT比较了透明质酸结合与传统ICSI。未报告活产情况。证据不足以表明两组在临床妊娠率上是否存在差异（RR 1.01，95%CI 0.84至1.22，一项RCT，482名女性）。该证据被认为质量较低，主要是由于方法和结果报告不佳。流产数据不明确，未报告胎儿异常率。另一项RCT比较了两种不同的透明质酸结合技术，即SpermSlow和生理性卵胞浆内单精子注射（PISCI）。证据不足以表明两组在活产率（RR 1.16，95%CI 0.65至2.05，一项RCT，99名女性）、临床妊娠率（RR 1.07，95%CI 0.67至1.71，一项RCT，99名女性）或流产率（RR 0.76，95%CI 0.24至2.44，一项RCT，41名女性）上是否存在差异。这些比较的证据被认为质量较低，因为它受到研究方法不精确和报告不佳的限制。未报告胎儿异常率。
证据不足，无法让综述作者确定通过透明质酸结合筛选的精子是否能改善ART中的活产或妊娠结局，且没有关于不良反应的明确数据。证据也不足以表明SpermSlow和PISCI这两种透明质酸结合方法在疗效上是否存在差异。未找到评估通过精子凋亡、精子双折射或表面电荷进行精子筛选的随机证据。需要进行质量合适的进一步研究，以评估这些先进的精子筛选技术中是否有任何一种可推荐用于临床实践。
