Boomsma Carolien M, Cohlen Ben J, Farquhar Cindy
Obstetrics and Gynaecology, Bravis Hospital, Boerhaaveplein 1, Bergen op Zoom, Netherlands, 4624 VT.
Cochrane Database Syst Rev. 2019 Oct 15;10(10):CD004507. doi: 10.1002/14651858.CD004507.pub4.
Semen preparation techniques for assisted reproduction, including intrauterine insemination (IUI), were developed to select the motile morphologically normal spermatozoa. The yield of many motile, morphologically normal spermatozoa might influence treatment choices and therefore outcomes.
To compare the effectiveness of three different semen preparation techniques (gradient; swim-up; wash and centrifugation) on clinical outcomes (live birth rate; clinical pregnancy rate) in subfertile couples undergoing IUI.
We searched the Cochrane Gynaecology and Fertility Group (CGFG) trials register, CENTRAL, MEDLINE, Embase, Science Direct Database, National Research Register, Biological Abstracts and clinical trial registries in March 2019, and checked references and contacted study authors to identify additional studies.
We included randomised controlled trials (RCTs) comparing the efficacy in terms of clinical outcomes of semen preparation techniques used for subfertile couples undergoing IUI.
We used standard methodological procedures recommended by Cochrane. The primary review outcomes are live birth rate and clinical pregnancy rate per couple.
We included seven RCTS in the review; we included six of these, totalling 485 couples, in the meta-analysis. No trials reported the primary outcome of live birth. The evidence was of very low-quality. The main limitations were (unclear) risk of bias, signs of imprecision and inconsistency in results among studies and the small number of studies/participants included.Swim-up versus gradient technique Considering the quality of evidence, we are uncertain whether there was a difference between clinical pregnancy rates (CPR) for swim-up versus a gradient technique (odds ratio (OR) 0.83, 95% CI 0.51 to 1.35; I² = 71%; 4 RCTs, 370 participants; very low-quality evidence). The results suggest that if the chance of pregnancy after the use of a gradient technique is assumed to be 24%, the chance of pregnancy after using the swim-up technique is between 14% and 30%. We are uncertain whether there was a real difference between ongoing pregnancy rates per couple (OR 0.39, 95% CI 0.19 to 0.82; heterogeneity not applicable; 1 RCT, 223 participants; very low-quality evidence). Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates (MPR) per couple comparing a swim-up versus gradient technique (MPR per couple 0% versus 0%; 1 RCT, 25 participants; very low-quality of evidence). Considering the quality of evidence, we are also uncertain whether there was a difference between miscarriage rates (MR) per couple comparing a swim-up versus gradient technique (OR 0.85, 95% CI 0.28 to 2.59; I² = 44%; 3 RCTs, 330 participants; very low-quality evidence). No studies reported on ectopic pregnancy rate, fetal abnormalities or infection rate.Swim-up versus wash techniqueConsidering the quality of evidence, we are uncertain whether there is a difference in clinical pregnancy rates after a swim-up technique versus wash and centrifugation (OR 0.41, 95% CI 0.15 to 1.13; I² = 55%; 2 RCTs, 78 participants; very low-quality evidence). The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 38%, the chance of pregnancy after using the swim-up technique is between 9% and 41%. Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates between swim-up technique versus wash technique (OR 0.49, 95% CI 0.02 to 13.28; heterogeneity not applicable; 1 RCT, 26 participants; very low-quality evidence). Miscarriage rate was only reported by one study: no miscarriages were reported in either treatment arm. No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate.Gradient versus wash techniqueConsidering the quality of evidence, we are uncertain whether there is a difference in clinical pregnancy rates after a gradient versus wash and centrifugation technique (OR 1.78, 95% CI 0.58 to 5.46; I² = 52%; 2 RCTs, 94 participants; very low-quality evidence). The results suggest that if the chance of pregnancy after the use of a wash technique is assumed to be 13%, the chance of pregnancy after using the gradient technique is between 8% and 46%. Considering the quality of evidence, we are uncertain whether there was a difference between multiple pregnancy rates per couple between the treatment groups (OR 0.33, 95% CI 0.01 to 8.83; very low-quality evidence). Considering the quality of evidence, we are also uncertain whether there was a difference between miscarriage rates per couple between the treatment groups (OR 6.11, 95% CI 0.27 to 138.45; very low-quality evidence). No studies reported on ongoing pregnancy rate, ectopic pregnancy rate, fetal abnormalities or infection rate.
AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend any specific semen preparation technique: swim-up versus gradient versus wash and centrifugation technique. No studies reported on live birth rates. Considering the quality of evidence (very low), we are uncertain whether there is a difference in clinical pregnancy rates, ongoing pregnancy rates, multiple pregnancy rates or miscarriage rates per couple) between the three sperm preparation techniques. Further randomised trials are warranted that report live birth data.
辅助生殖的精液制备技术,包括宫腔内人工授精(IUI),旨在挑选出形态正常且具有运动能力的精子。大量形态正常且具有运动能力的精子的产出量可能会影响治疗方案的选择,进而影响治疗结果。
比较三种不同精液制备技术(梯度离心法;上游法;洗涤离心法)对接受IUI的不育夫妇临床结局(活产率;临床妊娠率)的有效性。
我们检索了Cochrane妇科与生育组(CGFG)试验注册库、CENTRAL、MEDLINE、Embase、科学Direct数据库、国家研究注册库、生物学文摘以及临床试验注册库,检索时间为2019年3月,并检查参考文献并联系研究作者以识别其他研究。
我们纳入了比较用于接受IUI的不育夫妇的精液制备技术在临床结局方面疗效的随机对照试验(RCT)。
我们采用了Cochrane推荐的标准方法程序。主要的综述结局是每对夫妇的活产率和临床妊娠率。
我们在综述中纳入了7项RCT;我们将其中6项纳入荟萃分析,共计485对夫妇。没有试验报告活产这一主要结局。证据质量非常低。主要局限性在于(不明确的)偏倚风险、结果的不精确迹象和研究间的不一致性以及纳入的研究/参与者数量较少。
上游法与梯度离心法
考虑到证据质量,我们不确定上游法与梯度离心法在临床妊娠率方面是否存在差异(优势比(OR)0.83,95%置信区间0.51至1.35;I² = 71%;4项RCT,370名参与者;证据质量非常低)。结果表明,如果假设使用梯度离心法后的妊娠几率为24%,那么使用上游法后的妊娠几率在14%至30%之间。我们不确定每对夫妇的持续妊娠率之间是否存在真正差异(OR 0.39,95%置信区间0.19至0.82;异质性不适用;1项RCT,223名参与者;证据质量非常低)。考虑到证据质量,我们不确定上游法与梯度离心法相比,每对夫妇的多胎妊娠率之间是否存在差异(每对夫妇的多胎妊娠率0%对0%;1项RCT,25名参与者;证据质量非常低)。考虑到证据质量,我们也不确定上游法与梯度离心法相比,每对夫妇的流产率之间是否存在差异(OR 0.85,95%置信区间0.28至2.59;I² = 44%;3项RCT,330名参与者;证据质量非常低)。没有研究报告异位妊娠率、胎儿异常或感染率。
上游法与洗涤法
考虑到证据质量,我们不确定上游法与洗涤离心法在临床妊娠率方面是否存在差异(OR 0.41,95%置信区间0.15至1.13;I² = 55%;2项RCT,78名参与者;证据质量非常低)。结果表明,如果假设使用洗涤法后的妊娠几率为38%,那么使用上游法后的妊娠几率在9%至41%之间。考虑到证据质量,我们不确定上游法与洗涤法在多胎妊娠率之间是否存在差异(OR 0.49,95%置信区间0.02至13.28;异质性不适用;1项RCT,26名参与者;证据质量非常低)。只有一项研究报告了流产率:两个治疗组均未报告流产情况。没有研究报告持续妊娠率、异位妊娠率、胎儿异常或感染率。
梯度离心法与洗涤法
考虑到证据质量,我们不确定梯度离心法与洗涤离心法在临床妊娠率方面是否存在差异(OR 1.78,95%置信区间0.58至5.46;I² = 52%;2项RCT,94名参与者;证据质量非常低)。结果表明,如果假设使用洗涤法后的妊娠几率为13%,那么使用梯度离心法后的妊娠几率在8%至46%之间。考虑到证据质量,我们不确定治疗组之间每对夫妇的多胎妊娠率是否存在差异(OR 0.33,95%置信区间0.01至8.83;证据质量非常低)。考虑到证据质量,我们也不确定治疗组之间每对夫妇的流产率是否存在差异(OR 6.11,95%置信区间0.27至138.45;证据质量非常低)。没有研究报告持续妊娠率、异位妊娠率、胎儿异常或感染率。
没有足够的证据推荐任何特定的精液制备技术:上游法与梯度离心法与洗涤离心法。没有研究报告活产率。考虑到证据质量(非常低),我们不确定三种精子制备技术在每对夫妇的临床妊娠率、持续妊娠率、多胎妊娠率或流产率方面是否存在差异。有必要进行进一步的随机试验并报告活产数据。