BACKGROUND The positive effects of growth hormone (GH) on IVF are often attributed to improvements in oocyte and embryo quality. While emerging evidence emphasizes GH-induced improvements in the endometrium, these results are controversial. OBJECTIVE AND RATIONALE This meta-analysis aimed to evaluate whether GH administration improved endometrial function and reproductive outcomes during IVF cycles and to thus guide clinical practice. SEARCH METHODS A literature search in the Cochrane Central Register of Controlled Trials, PubMed and Embase was performed through to 30 November 2021, without language restrictions. Randomized controlled trials (RCTs) evaluating the effects of GH on IVF outcomes were included. Risk of bias and quality of evidence (QoE) were assessed according to the Cochrane Collaboration’s tool and the Grading of Recommendations Assessment, Development and Evaluation system. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed by random-effects models. OUTCOMES A total of 25 trials with 2424 women were included. Seventeen RCTs with poor responders (n = 1723) showed that GH administration significantly increased endometrial thickness (EMT) (MD = 0.38, 95% CI: 0.18–0.59; moderate QoE), which contributed to an improved live birth rate (OR = 1.67, 95% CI: 1.13–2.49; very low QoE) and clinical pregnancy rate (CPR) (OR = 1.97, 95% CI: 1.43–2.72; low QoE). Subgroup analyses showed a dose- and time-dependent relationship between GH cotreatment and IVF outcomes; the optimal recommendation for improving CPR was consistent with that for EMT, rather than for oocytes and embryos. Hence, GH might improve fertility via effects on the endometrium. Administration of GH daily from the follicular phase of previous cycle until the hCG trigger with < 5 IU/day led to a thicker endometrium and a greater chance of becoming pregnant, while 5–10 IU/day or administration from the luteal phase of the previous cycle until the hCG trigger resulted in higher oocyte and embryo quality. Poor responders might benefit from cotreatment with the GnRH agonist long protocol more than other stimulation protocols. Pooled data from four trials (n = 354) on women with a thin endometrium indicated that improved endometrial function might be critical for improving reproductive outcomes during GH treatment, as no improvements in embryo quality were found. GH administration not only increased EMT (MD = 1.48, 95% CI: 1.21–1.75; moderate QoE) but also promoted endometrial morphology (OR = 2.67, 95% CI: 1.36–5.23; low QoE) and perfusion (OR = 5.84, 95% CI: 1.30–26.17; low QoE), thereby improving the CPR (OR = 2.71, 95% CI: 1.69–4.34; P < 0.0001; low QoE). There was insufficient evidence to reach a conclusion regarding the effects of GH in normal responders (n = 80). Due to obvious improvements in the CPR, women with a thin endometrium might be the most appropriate population to benefit from GH administration. WIDER IMPLICATIONS Improving endometrial function might be another vital mechanism by which GH improves IVF outcomes. Optimal treatment should be offered to the target population according to their personal conditions and needs. The QoE was moderate to very low, due to limited sample sizes and methodological problems; thus, the results should be interpreted with caution. More rigorous RCTs with large sample sizes are needed to confirm the effects and determine optimal GH protocols.

中文翻译：

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施用生长激素可改善接受体外受精的女性的子宫内膜功能：一项系统评价和荟萃分析

背景技术 生长激素 (GH) 对 IVF 的积极影响通常归因于卵母细胞和胚胎质量的改善。虽然新出现的证据强调 GH 诱导的子宫内膜改善，但这些结果是有争议的。目的和基本原理 本荟萃分析旨在评估 GH 给药是否改善了 IVF 周期中的子宫内膜功能和生殖结果，从而指导临床实践。检索方法 截至 2021 年 11 月 30 日，在 Cochrane 对照试验中央登记册、PubMed 和 Embase 中进行了文献检索，没有语言限制。包括评估 GH 对 IVF 结果影响的随机对照试验 (RCT)。偏倚风险和证据质量 (QoE) 是根据 Cochrane 协作网的工具和建议分级评估、开发和评估系统进行评估的。通过随机效应模型评估优势比 (OR) 和均值差 (MD) 以及 95% 置信区间 (CI)。结果 共纳入 25 项试验，共有 2424 名女性。17 项反应不佳的随机对照试验 (n = 1723) 表明，GH 给药显着增加了子宫内膜厚度 (EMT)（MD = 0.38，95% CI：0.18–0.59；中等 QoE），这有助于提高活产率（OR = 1.67 , 95% CI: 1.13–2.49; 极低的 QoE) 和临床妊娠率 (CPR) (OR = 1.97, 95% CI: 1.43–2.72; 低 QoE)。亚组分析显示 GH 联合治疗与 IVF 结果之间存在剂量和时间依赖关系；改善 CPR 的最佳建议与 EMT 一致，而不是卵母细胞和胚胎。因此，GH 可能通过影响子宫内膜来提高生育能力。从前一个周期的卵泡期每天给予 GH，直到 hCG 触发为 5 IU/天导致子宫内膜变厚并增加怀孕的机会，而 5-10 IU/天或从前一个周期的黄体期给药直到 hCG 触发导致更高的卵母细胞和胚胎质量。与其他刺激方案相比，反应较差的患者可能会从与 GnRH 激动剂长期方案的联合治疗中获益更多。来自四项针对子宫内膜薄的女性的试验（n = 354）的汇总数据表明，改善子宫内膜功能可能对于改善 GH 治疗期间的生殖结果至关重要，因为没有发现胚胎质量的改善。GH 给药不仅增加了 EMT（MD = 1.48，95% CI：1.21-1.75；中等 QoE），还促进了子宫内膜形态（OR = 2.67，95% CI：1.36-5.23；低 QoE）和灌注（OR = 5.84， 95% CI：1.30–26.17；低 QoE），从而改善 CPR（OR = 2.71，95% CI：1.69–4.34；P < 0.0001；低 QoE）。没有足够的证据得出关于 GH 对正常反应者 (n = 80) 的影响的结论。由于 CPR 的明显改善，子宫内膜薄的女性可能是最适合从 GH 给药中获益的人群。更广泛的意义 改善子宫内膜功能可能是 GH 改善 IVF 结果的另一个重要机制。应根据目标人群的个人条件和需要向他们提供最佳治疗。由于样本量有限和方法问题，QoE 中等到极低；因此，应谨慎解释结果。需要更严格的大样本随机对照试验来确认效果并确定最佳 GH 方案。