BACKGROUND Despite great advances in assisted reproductive technology, poor ovarian response (POR) is still considered as one of the most challenging tasks in reproductive medicine. OBJECTIVE AND RATIONALE The aim of this systemic review is to evaluate the role of different adjuvant treatment strategies on the probability of pregnancy achievement in poor responders undergoing IVF. Randomized controlled trials (RCTs) comparing 10 adjuvant treatments [testosterone, dehydroepiandrosterone (DHEA), letrozole, recombinant LH, recombinant hCG, oestradiol, clomiphene citrate, progesterone, growth hormone (GH) and coenzyme Q10 (CoQ10)] were included. SEARCH METHODS Relevant studies published in the English language were comprehensively selected using PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) until 11 July 2018. We included studies that investigated various adjuvant agents, including androgen and androgen-modulating agents, oestrogen, progesterone, clomiphene citrate, GH and CoQ10, during IVF treatment and reported subsequent pregnancy outcomes. The administration of GnRH analogs and gonadotrophins without adjuvant treatment was set as the control. We measured study quality based on the methodology and categories listed in the Cochrane Collaboration Handbook. This review protocol was registered with PROSPERO (CRD42018086217). OUTCOMES Of the 1124 studies initially identified, 46 trials reporting on 6312 women were included in this systematic review, while 19 trials defining POR using the Bologna criteria reporting 2677 women were included in the network meta-analysis. Compared with controls, DHEA and CoQ10 treatments resulted in a significantly higher chance of clinical pregnancy [odds ratio (OR) 2.46, 95% CI 1.16 to 5.23; 2.22, 1.08-4.58, respectively]. With regard to the number of retrieved oocytes, HCG, oestradiol and GH treatments had the highest number of oocytes retrieved [weighted mean difference (WMD) 2.08, 0.72 to 3.44; 2.02, 0.23 to 3.81; 1.72, 0.98 to 2.46, compared with controls, respectively]. With regard to the number of embryos transferred, testosterone and GH treatment led to the highest number of embryos transferred (WMD 0.72, 0.11 to 1.33; 0.67, 0.43 to 0.92; compared with controls, respectively). Moreover, GH resulted in the highest oestradiol level on the HCG day (WMD 797.63, 466.45 to 1128.81, compared with controls). Clomiphene citrate, letrozole and GH groups used the lowest dosages of gonadotrophins for ovarian stimulation (WMD 1760.00, -2890.55 to -629.45; -1110.17, -1753.37 to -466.96; -875.91, -1433.29 to -282.52; compared with controls, respectively). CoQ10 led to the lowest global cancelation rate (OR 0.33, 0.15 to 0.74, compared with controls). WIDER IMPLICATIONS For patients with POR, controlled ovarian stimulation protocols using adjuvant treatment with DHEA, CoQ10 and GH showed better clinical outcomes in terms of achieving pregnancy, and a lower dosage of gonadotrophin required for ovulation induction. Furthermore, high-level RCT studies using uniform standards for POR need to be incorporated into future meta-analyses.

中文翻译：

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接受IVF的不良反应者在卵巢刺激中的辅助治疗策略：系统评价和网络荟萃分析。

背景技术尽管辅助生殖技术取得了巨大进步，但是卵巢反应差（POR）仍然被认为是生殖医学中最具挑战性的任务之一。目的和理由本系统评价的目的是评估在接受IVF的较弱反应者中，不同辅助治疗策略对实现怀孕机率的作用。包括比较10种辅助治疗的随机对照试验（RCT）[睾丸激素，脱氢表雄酮（DHEA），来曲唑，重组LH，重组hCG，雌二醇，克罗米芬柠檬酸盐，孕酮，生长激素（GH）和辅酶Q10（CoQ10）]。搜索方法截至2018年7月11日，使用PubMed，Embase和Cochrane对照试验中央注册系统（CENTRAL）全面选择以英语发表的相关研究。我们纳入了在IVF治疗期间调查各种佐剂（包括雄激素和雄激素调节剂，雌激素，孕激素，克罗米芬，GH和CoQ10）的研究，并报告了随后的妊娠结局。将未经辅助治疗的GnRH类似物和促性腺激素的给药作为对照。我们根据《 Cochrane合作手册》中列出的方法和类别对研究质量进行了评估。该审核协议已在PROSPERO（CRD42018086217）中注册。结果在最初确定的1124项研究中，该系统评价包括46项报告了6312名妇女的试验，而19项使用Bologna标准定义POR的试验报告了2677名妇女，该研究纳入了网络荟萃分析。与对照相比，DHEA和CoQ10治疗导致临床妊娠的几率显着更高[几率（OR）2.46，95％CI 1.16至5.23；2.22、1.08-4.58]。对于回收的卵母细胞数量，HCG，雌二醇和GH处理的卵母细胞回收率最高[加权平均差异（WMD）为2.08，0.72至3.44；2.02，0.23至3.81；与对照组相比分别为1.72、0.98至2.46]。关于转移的胚胎数量，睾丸激素和GH处理导致转移的胚胎数量最高（与对照相比，WMD分别为0.72、0.11至1.33、0.67、0.43至0.92）。此外，GH导致HCG日的雌二醇水平最高（与对照组相比，WMD 797.63、466.45至1128.81）。柠檬酸克罗米芬 来曲唑和GH组使用最低剂量的促性腺激素刺激卵巢（分别与对照组相比，WMD 1760.00，-2890.55至-629.45; -1110.17，-1753.37至-466.96; -875.91，-1433.29至-282.52）。辅酶Q10导致总体取消率最低（与对照组相比，OR为0.33，从0.15到0.74）。对POR患者的影响，采用DHEA，CoQ10和GH辅助治疗的可控卵巢刺激方案在实现妊娠方面表现出更好的临床效果，并且促排卵所需的促性腺激素剂量更低。此外，使用统一的POR标准进行的高级RCT研究需要纳入未来的荟萃分析中。辅酶Q10导致总体取消率最低（与对照组相比，OR为0.33，从0.15到0.74）。对POR患者的影响，采用DHEA，CoQ10和GH辅助治疗的可控卵巢刺激方案在实现妊娠方面表现出更好的临床效果，并且促排卵所需的促性腺激素剂量更低。此外，使用统一的POR标准进行的高级RCT研究需要纳入未来的荟萃分析中。辅酶Q10导致总体取消率最低（与对照组相比，OR为0.33，从0.15到0.74）。对POR患者的影响，采用DHEA，CoQ10和GH辅助治疗的可控卵巢刺激方案在实现妊娠方面表现出更好的临床效果，并且促排卵所需的促性腺激素剂量更低。此外，使用统一的POR标准进行的高级RCT研究需要纳入未来的荟萃分析中。