背景:辅助生殖技术(ART)领域的从业者不断寻求替代或辅助治疗以改善ART结果。这篇Cochrane评论调查了两种天然产生的激素的合成版本的辅助使用,脱氢表雄酮(DHEA)和睾酮(T),辅助生殖。建议类固醇激素通过积极影响卵泡对促性腺激素刺激的反应来提高受孕率。这可能会导致更高的卵母细胞产量,随后,怀孕的机会增加。
目的:评估DHEA和T作为辅助生殖的不孕妇女的预治疗或联合治疗的有效性和安全性。
方法:截至2024年1月8日,我们搜索了以下电子数据库:妇科和生育小组(CGF)专业注册,中部,MEDLINE,Embase,PsycINFO,和正在进行的审判登记处。我们还搜索了引文索引,WebofScience,PubMed,OpenGrey我们搜索了相关研究的参考列表,并联系了该领域的专家进行任何其他试验。没有语言限制。
方法:随机对照试验(RCT)将DHEA或T作为辅助治疗与任何其他积极干预措施进行比较,安慰剂,或者在接受辅助生殖的女性中没有治疗。
方法:两位综述作者独立选择了研究,提取相关数据,并评估偏见的风险。我们使用固定效应模型汇集了研究数据。我们计算了每个二分法结果的比值比(OR)。分析按治疗类型分层。我们使用GRADE方法评估了主要发现的证据的确定性。
结果:我们纳入了29项随机对照试验。干预组有1599名妇女,对照组有1469名妇女。除了三项试验,试验参与者是被认定为标准体外受精(IVF)方案反应不良的女性.纳入的试验比较了T或DHEA治疗与安慰剂或不治疗。DHEA治疗前与安慰剂/不治疗:DHEA可能导致活产/持续妊娠率几乎没有差异(OR1.30,95%置信区间(CI)0.95至1.76;I²=16%,9项随机对照试验,N=1433,中度确定性证据)。这表明,在安慰剂或不治疗的情况下,活产/持续怀孕的可能性为12%的女性,使用DHEA的女性活产/持续妊娠率将在12%至20%之间.DHEA可能不会降低流产率(OR0.85,95%CI0.53至1.37;I²=0%,10个随机对照试验,N=1601,中度确定性证据)。DHEA可能导致临床妊娠率几乎没有差异(OR1.18,95%CI0.93至1.49;I²=0%,13项随机对照试验,N=1886,中度确定性证据)。这表明,在安慰剂或不治疗的临床怀孕机会为17%的女性中,使用DHEA的女性的临床妊娠率将在16%至24%之间.我们非常不确定DHEA对多胎妊娠的影响(OR3.05,95%CI0.47至19.66;7项RCT,N=463,确定性非常低的证据)。T治疗前与安慰剂/不治疗:T可能会提高活产率(OR2.53,95%CI1.61至3.99;I²=0%,8个随机对照试验,N=716,中度确定性证据)。这表明,在安慰剂或不治疗的情况下,活产机会为10%的女性,使用T的妇女的活产率将在15%至30%之间。T可能不会降低流产率(OR1.63,95%CI0.76至3.51;I²=0%,9项随机对照试验,N=755,中度确定性证据)。T可能会增加临床妊娠率(OR2.17,95%CI1.54至3.06;I²=0%,13项随机对照试验,N=1152,中度确定性证据)。这表明,在安慰剂或不治疗的情况下,临床妊娠几率为12%的女性,使用T的女性的临床妊娠率将在17%至29%之间。我们非常不确定T对多胎妊娠的影响(OR2.56,95%CI0.59至11.20;5个RCT,N=449,非常低的确定性证据)。我们不确定T与雌二醇或T与雌二醇口服避孕药的作用。证据的确定性中等到很低,主要限制是纳入的试验缺乏盲法,研究方法报告不充分,以及试验中事件和样本量较低。不良事件的数据很少;任何报告的事件都是次要的。
结论:T前治疗可能会改善,用DHEA预处理可能几乎没有差异,在接受IVF的女性中,活产和临床妊娠率被确定为反应不良的女性。DHEA和T可能不会降低接受IVF治疗的女性的流产率。DHEA和T对多胎妊娠的影响尚不确定。有关不良事件的数据非常有限;任何报告的事件都是轻微的。需要研究确定T治疗的最佳持续时间。未来的研究应包括不良事件和多胎妊娠的数据收集。
Practitioners in the field of assisted reproductive technology (ART) continually seek alternative or adjunct treatments to improve ART outcomes. This Cochrane review investigates the adjunct use of synthetic versions of two naturally produced hormones,
dehydroepiandrosterone (DHEA) and testosterone (T), in assisted reproduction. Steroid hormones are proposed to increase conception rates by positively affecting follicular response to gonadotrophin stimulation. This may lead to a greater oocyte yield and, subsequently, an increased chance of pregnancy.
To assess the effectiveness and safety of DHEA and T as pre- or co-treatments in infertile women undergoing assisted reproduction.
We searched the following electronic databases up to 8 January 2024: the Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, and trial registries for ongoing trials. We also searched citation indexes, Web of Science, PubMed, and OpenGrey. We searched the reference lists of relevant studies and contacted experts in the field for any additional trials. There were no language restrictions.
Randomised controlled trials (RCTs) comparing DHEA or T as an adjunct treatment to any other active intervention, placebo, or no treatment in women undergoing assisted reproduction.
Two review authors independently selected studies, extracted relevant data, and assessed risk of bias. We pooled data from studies using fixed-effect models. We calculated odds ratios (ORs) for each dichotomous outcome. Analyses were stratified by type of treatment. We assessed the certainty of evidence for the main findings using GRADE methods.
We included 29 RCTs. There were 1599 women in the intervention group and 1469 in the control group. Apart from three trials, the trial participants were women identified as \'poor responders\' to standard in vitro fertilisation (IVF) protocols. The included trials compared either T or DHEA treatment with placebo or no treatment. Pre-treatment with DHEA versus placebo/no treatment: DHEA likely results in little to no difference in live birth/ongoing pregnancy rates (OR 1.30, 95% confidence interval (CI) 0.95 to 1.76; I² = 16%, 9 RCTs, N = 1433, moderate certainty evidence). This suggests that in women with a 12% chance of live birth/ongoing pregnancy with placebo or no treatment, the live birth/ongoing pregnancy rate in women using DHEA will be between 12% and 20%. DHEA likely does not decrease miscarriage rates (OR 0.85, 95% CI 0.53 to 1.37; I² = 0%, 10 RCTs, N =1601, moderate certainty evidence). DHEA likely results in little to no difference in clinical pregnancy rates (OR 1.18, 95% CI 0.93 to 1.49; I² = 0%, 13 RCTs, N = 1886, moderate certainty evidence). This suggests that in women with a 17% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using DHEA will be between 16% and 24%. We are very uncertain about the effect of DHEA on multiple pregnancy (OR 3.05, 95% CI 0.47 to 19.66; 7 RCTs, N = 463, very low certainty evidence). Pre-treatment with T versus placebo/no treatment: T likely improves live birth rates (OR 2.53, 95% CI 1.61 to 3.99; I² = 0%, 8 RCTs, N = 716, moderate certainty evidence). This suggests that in women with a 10% chance of live birth with placebo or no treatment, the live birth rate in women using T will be between 15% and 30%. T likely does not decrease miscarriage rates (OR 1.63, 95% CI 0.76 to 3.51; I² = 0%, 9 RCTs, N = 755, moderate certainty evidence). T likely increases clinical pregnancy rates (OR 2.17, 95% CI 1.54 to 3.06; I² = 0%, 13 RCTs, N = 1152, moderate certainty evidence). This suggests that in women with a 12% chance of clinical pregnancy with placebo or no treatment, the clinical pregnancy rate in women using T will be between 17% and 29%. We are very uncertain about the effect of T on multiple pregnancy (OR 2.56, 95% CI 0.59 to 11.20; 5 RCTs, N = 449, very low certainty evidence). We are uncertain about the effect of T versus oestradiol or T versus oestradiol + oral contraceptive pills. The certainty of the evidence was moderate to very low, the main limitations being lack of blinding in the included trials, inadequate reporting of study methods, and low event and sample sizes in the trials. Data on adverse events were sparse; any reported events were minor.
Pre-treatment with T likely improves, and pre-treatment with DHEA likely results in little to no difference, in live birth and clinical pregnancy rates in women undergoing IVF who have been identified as poor responders. DHEA and T probably do not decrease miscarriage rates in women under IVF treatment. The effects of DHEA and T on multiple pregnancy are uncertain. Data regarding adverse events were very limited; any reported events were minor. Research is needed to identify the optimal duration of treatment with T. Future studies should include data collection on adverse events and multiple pregnancy.