BACKGROUND The beneficial effects of hormonal therapy in stimulating spermatogenesis in patients with non-obstructive azoospermia (NOA) and either normal gonadotrophins or hypergonadotropic hypogonadism prior to surgical sperm retrieval (SSR) is controversial. Although the European Association of Urology guidelines state that hormone stimulation is not recommended in routine clinical practice, a significant number of patients undergo empiric therapy prior to SSR. The success rate for SSR from microdissection testicular sperm extraction is only 40-60%, thus hormonal therapy could prove to be an effective adjunctive therapy to increase SSR rates. OBJECTIVE AND RATIONALE The primary aim of this systematic review and meta-analysis was to compare the SSR rates in men with NOA (excluding those with hypogonadotropic hypogonadism) receiving hormone therapy compared to placebo or no treatment. The secondary objective was to compare the effects of hormonal therapy in normogonadotropic and hypergonadotropic NOA men. SEARCH METHODS A literature search was performed using the Medline, Embase, Web of Science and Clinicaltrials.gov databases from 01 January 1946 to 17 September 2020. We included all studies where hormone status was confirmed. We excluded non-English language and animal studies. Heterogeneity was calculated using I2 statistics and risk of bias was assessed using Cochrane tools. We performed a meta-analysis on all the eligible controlled trials to determine whether hormone stimulation (irrespective of class) improved SSR rates and also whether this was affected by baseline hormone status (hypergonadotropic versus normogonadotropic NOA men). Sensitivity analyses were performed when indicated. OUTCOMES A total of 3846 studies were screened and 22 studies were included with 1706 participants. A higher SSR rate in subjects pre-treated with hormonal therapy was observed (odds ratio (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03) and this trend persisted when excluding a study containing only men with Klinefelter syndrome (OR 1.90, 95% CI: 1.03-3.51, P = 0.04). However, the subgroup analysis of baseline hormone status demonstrated a significant improvement only in normogonadotropic men (OR 2.13, 95% CI: 1.10-4.14, P = 0.02) and not in hypergonadotropic patients (OR 1.73, 95% CI: 0.44-6.77, P = 0.43). The literature was at moderate or severe risk of bias. WIDER IMPLICATIONS This meta-analysis demonstrates that hormone therapy is not associated with improved SSR rates in hypergonadotropic hypogonadism. While hormone therapy improved SSR rates in eugonadal men with NOA, the quality of evidence was low with a moderate to high risk of bias. Therefore, hormone therapy should not be routinely used in men with NOA prior to SSR and large scale, prospective randomized controlled trials are needed to validate the meta-analysis findings.

中文翻译：

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激素疗法是否能提高非梗阻性无精子症男性的精子取回率：系统评价和荟萃分析。

背景激素治疗在非梗阻性无精子症 (NOA) 和正常促性腺激素或高促性腺激素性性腺功能减退症患者在手术取精 (SSR) 之前刺激精子发生的有益作用是有争议的。尽管欧洲泌尿外科协会指南指出在常规临床实践中不推荐激素刺激，但仍有大量患者在 SSR 之前接受经验性治疗。显微解剖睾丸精子提取的 SSR 成功率仅为 40-60%，因此激素疗法可被证明是提高 SSR 率的有效辅助疗法。目的和理由 本系统评价和荟萃分析的主要目的是比较接受激素治疗与安慰剂或不治疗的 NOA 男性（不包括促性腺功能减退症患者）的 SSR 率。次要目标是比较激素治疗对正常促性腺激素和高促性腺激素 NOA 男性的影响。检索方法 从 1946 年 1 月 1 日至 2020 年 9 月 17 日，使用 Medline、Embase、Web of Science 和 Clinicaltrials.gov 数据库进行文献检索。我们纳入了所有确认激素状态的研究。我们排除了非英语语言和动物研究。使用 I2 统计计算异质性，使用 Cochrane 工具评估偏倚风险。我们对所有符合条件的对照试验进行了荟萃分析，以确定激素刺激（不论类别）是否提高了 SSR 率，以及这是否受基线激素状态（高促性腺激素与正促性腺激素 NOA 男性）的影响。在需要时进行敏感性分析。结果 共筛选了 3846 项研究，纳入了 22 项研究，共有 1706 名参与者。在接受激素治疗的受试者中观察到更高的 SSR 率（优势比 (OR) 1.96, 95% CI: 1.08-3.56, P = 0.03）并且当排除仅包含克氏综合征男性的研究时，这种趋势仍然存在（OR 1.90, 95% CI: 1.03-3.51, P = 0.04)。然而，基线激素状态的亚组分析表明仅在正常促性腺激素的男性中有显着改善（OR 2.13, 95% CI: 1.10-4.14, P = 0. 02) 而不是在高促性腺激素患者中 (OR 1.73, 95% CI: 0.44-6.77, P = 0.43)。文献存在中度或重度偏倚风险。更广泛的意义 这项荟萃分析表明，激素治疗与提高促性腺激素性性腺功能减退症患者的 SSR 率无关。虽然激素治疗提高了患有 NOA 的性腺功能正常的男性的 SSR 率，但证据质量低，偏倚风险为中度至高度。因此，激素治疗不应常规用于 SSR 之前患有 NOA 的男性，需要进行大规模前瞻性随机对照试验来验证荟萃分析结果。更广泛的意义 这项荟萃分析表明，激素治疗与提高促性腺激素性性腺功能减退症患者的 SSR 率无关。虽然激素治疗提高了患有 NOA 的性腺功能正常的男性的 SSR 率，但证据质量低，偏倚风险为中度至高度。因此，激素治疗不应常规用于 SSR 之前患有 NOA 的男性，需要进行大规模前瞻性随机对照试验来验证荟萃分析结果。更广泛的意义 这项荟萃分析表明，激素治疗与提高促性腺激素性性腺功能减退症患者的 SSR 率无关。虽然激素治疗提高了患有 NOA 的性腺功能正常的男性的 SSR 率，但证据质量低，偏倚风险为中度至高度。因此，激素治疗不应常规用于 SSR 之前患有 NOA 的男性，需要进行大规模前瞻性随机对照试验来验证荟萃分析结果。