Verkuijlen Jolijn, Verhaak Christianne, Nelen Willianne L D M, Wilkinson Jack, Farquhar Cindy
Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, Nijmegen, Netherlands, 6525 GA.
Cochrane Database Syst Rev. 2016 Mar 31;3(3):CD011034. doi: 10.1002/14651858.CD011034.pub2.
Approximately one-fifth of all subfertile couples seeking fertility treatment show clinically relevant levels of anxiety, depression, or distress. Psychological and educational interventions are frequently offered to subfertile couples, but their effectiveness, both in improving mental health and pregnancy rates, is unclear.
To assess the effectiveness of psychological and educational interventions for subfertile couples on psychological and fertility treatment outcomes.
We searched (from inception to 2 April 2015) the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2015), MEDLINE, EMBASE, PsycINFO, EBSCO CINAHL, DARE, Web of Science, OpenGrey, LILACS, PubMed, and ongoing trials registers. We handsearched reference lists and contacted experts in the field.
We included published and unpublished randomised controlled trials (RCTs), cluster randomised trials, and cross-over trials (first phase) evaluating the effectiveness of psychological and educational interventions on psychological and fertility treatment outcomes in subfertile couples.
Two review authors independently assessed trial risk of bias and extracted data. We contacted study authors for additional information. Our primary outcomes were psychological measures (anxiety and depression) and fertility rates (live birth or ongoing pregnancy). We assessed the overall quality of the evidence using GRADE criteria.As we did not consider the included studies to be sufficiently similar to permit meaningful pooling, we summarised the results of the individual studies by presenting the median and interquartile range (IQR) of effects as well as the minimum and maximum values. We calculated standardised mean differences (SMDs) for continuous variables and odds ratios (ORs) for dichotomous outcomes.
We included 39 studies involving 4925 participants undergoing assisted reproductive technology. Studies were heterogeneous with respect to a number of factors, including nature and duration of interventions, participants, and comparator groups. As a result, we judged that pooling results would not result in a clinically meaningful estimate of a treatment effect. There were substantial methodological weaknesses in the studies, all of which were judged to be at high risk of bias for one or more quality assessment domains. There was concern about attrition bias (24 studies), performance bias for psychological outcomes (27 studies) and fertility outcomes (18 studies), and detection bias for psychological outcomes (26 studies). We therefore considered study-specific estimates of intervention effects to be unreliable. Thirty-three studies reported the outcome mental health. Only two studies reported the outcome live birth, and both of these had substantial attrition. One study reported ongoing pregnancy, again with substantial attrition. We have combined live birth and ongoing pregnancy in one outcome. Psychological outcomesStudies utilised a variety of measures of anxiety and depression. In all cases a low score denoted benefit from the intervention.SMDs for anxiety were as follows: psychological interventions versus attentional control or usual care: median (IQR) = -0.30 (-0.84 to 0.00), minimum value -5.13; maximum value 0.84, 17 RCTs, 2042 participants; educational interventions versus attentional control or usual care: median = 0.03, minimum value -0.38; maximum value 0.23, 4 RCTs, 330 participants.SMDs for depression were as follows: psychological interventions versus attentional control or usual care: median (IQR) = -0.45 (-0.68 to -0.08), minimum value -3.01; maximum value 1.23, 12 RCTs, 1160 participants; educational interventions versus attentional control or usual care: median = -0.33, minimum value -0.46; maximum value 0.17, 3 RCTs, 304 participants. Fertility outcomesWhen psychological interventions were compared with attentional control or usual care, ORs for live birth or ongoing pregnancy ranged from minimum value 1.13 to maximum value 10.05. No studies of educational interventions reported this outcome.
AUTHORS' CONCLUSIONS: The effects of psychological and educational interventions on mental health including distress, and live birth or ongoing pregnancy rates is uncertain due to the very low quality of the evidence. Existing trials of psychological and educational interventions for subfertility were generally poorly designed and executed, resulting in very serious risk of bias and serious inconsistency in study findings. There is a need for studies employing appropriate methodological techniques to investigate the benefits of these treatments for this population. In particular, attentional control groups should be employed, that is groups receiving a treatment that mimics the amount of time and attention received by the treatment group but is not thought to have a specific effect upon the participants, in order to distinguish between therapeutic and non-specific effects of interventions. Where attrition cannot be minimised, appropriate statistical techniques for handling drop-out must be applied. Failure to address these issues in study design has resulted in studies that do not provide a valid basis for answering questions about the effectiveness of these interventions.
在寻求生育治疗的所有不育夫妇中，约五分之一表现出具有临床意义的焦虑、抑郁或痛苦水平。心理和教育干预经常提供给不育夫妇，但其在改善心理健康和提高妊娠率方面的有效性尚不清楚。
评估心理和教育干预对不育夫妇心理及生育治疗结局的有效性。
我们检索了（从数据库建立至2015年4月2日）Cochrane妇科与生育组专业对照试验注册库、Cochrane对照试验中央注册库（CENTRAL；2015年第2期）、MEDLINE、EMBASE、PsycINFO、EBSCO CINAHL、DARE、科学引文索引、OpenGrey、LILACS、PubMed以及正在进行的试验注册库。我们手工检索了参考文献列表并联系了该领域的专家。
我们纳入了已发表和未发表的随机对照试验（RCT）、整群随机试验以及交叉试验（第一阶段），这些试验评估了心理和教育干预对不育夫妇心理及生育治疗结局的有效性。
两位综述作者独立评估试验的偏倚风险并提取数据。我们联系研究作者以获取更多信息。我们的主要结局是心理测量指标（焦虑和抑郁）以及生育率（活产或持续妊娠）。我们使用GRADE标准评估证据的总体质量。由于我们认为纳入的研究不够相似，无法进行有意义的合并，因此我们通过呈现效应的中位数和四分位间距（IQR）以及最小值和最大值来总结各个研究的结果。我们计算了连续变量的标准化均数差（SMD）和二分结局的比值比（OR）。
我们纳入了39项研究，涉及4925名接受辅助生殖技术的参与者。研究在多个因素方面存在异质性，包括干预的性质和持续时间、参与者以及对照人群。因此，我们判断合并结果不会得出具有临床意义的治疗效应估计值。这些研究存在大量方法学上的弱点，所有研究在一个或多个质量评估领域均被判定为高偏倚风险。人们担心存在失访偏倚（24项研究）、心理结局的实施偏倚（27项研究）和生育结局的实施偏倚（18项研究）以及心理结局的检测偏倚（26项研究）。因此，我们认为特定研究的干预效应估计值不可靠。33项研究报告了心理健康结局。只有两项研究报告了活产结局，且这两项研究均有大量失访。一项研究报告了持续妊娠结局，同样存在大量失访。我们将活产和持续妊娠合并为一个结局。心理结局研究使用了多种焦虑和抑郁测量指标。在所有情况下，低分表示干预有益。焦虑的标准化均数差如下：心理干预与注意力控制或常规护理相比：中位数（IQR）=-0.30（-0.84至0.00），最小值-5.13；最大值0.84，17项RCT，2042名参与者；教育干预与注意力控制或常规护理相比：中位数=0.03，最小值-0.38；最大值0.23，4项RCT，330名参与者。抑郁的标准化均数差如下：心理干预与注意力控制或常规护理相比：中位数（IQR）=-0.45（-0.68至-0.08），最小值-3.01；最大值1.23，12项RCT，1160名参与者；教育干预与注意力控制或常规护理相比：中位数=-0.33，最小值-0.46；最大值0.17，3项RCT，304名参与者。生育结局当将心理干预与注意力控制或常规护理进行比较时，活产或持续妊娠的比值比范围为最小值1.13至最大值10.05。没有关于教育干预的研究报告此结局。
由于证据质量极低，心理和教育干预对包括痛苦在内的心理健康以及活产或持续妊娠率的影响尚不确定。现有的不育心理和教育干预试验通常设计和实施不佳，导致存在非常严重的偏倚风险以及研究结果的严重不一致性。需要采用适当方法学技术的研究来调查这些治疗对该人群的益处。特别是，应采用注意力控制组，即接受一种模拟治疗组所接受的时间和注意力量但被认为对参与者没有特定影响的治疗的组，以便区分干预的治疗效果和非特异性效果。在无法将失访降至最低的情况下，必须应用适当的统计技术来处理失访问题。在研究设计中未能解决这些问题导致研究无法为回答这些干预措施的有效性问题提供有效的依据。
