Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts.
Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts.
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DOI：
10.1093/humrep/dew284
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Laan M
中科院分区：
文献类型：
--
作者：
Punab M;Poolamets O;Paju P;Vihljajev V;Pomm K;Ladva R;Korrovits P;Laan M
严重男性因素不育的主要原因是什么？虽然40%的患者有不育的原发原因，根据其影响的严重程度可分为三组，但约75%的少精子症患者仍为特发性。很少有大规模的流行病学研究分析男性因素不育症的原因。2005年至2013年，塔尔图大学医院男科中心进行了一项前瞻性的临床流行病学研究，招募了未能怀孕超过≥12个月的夫妇的男性伴侣。在8518例患者中，1737例(20.4%)被诊断为严重男性因素不育症。生育控制的参照组由325名孕妇的伴侣组成。不孕症患者的平均年龄为33.2±67.3岁，生育对照组的平均年龄为31.7±66.3岁。所有参与者都接受了标准化的男科检查，同时还进行了结构化的医学访谈。激素分析包括血清促卵泡激素、促黄体生成素和睾酮。精液质量是根据世界卫生组织的建议确定的。对精子≤浓度为500万/ml的患者进行了染色体异常和Y染色体微缺失筛查。在1737例患者中，695例(~40%)确定了不孕症的主要原因。分析的原因可分为绝对原因(继发性性腺功能减退、遗传因素、精道梗阻)、严重原因(肿瘤性疾病、严重性功能障碍)和合理原因(生殖道先天性异常、后天性或继发性睾丸损害)。后者也在11名(3.4%)已证实有生育能力的男性(诊断为单侧隐睾症、睾丸癌、睾丸炎、腮腺炎睾丸炎)中检测到。对最严重的生精障碍背后的原因有较好的了解；归类原因：46/46例(100%)为无精子症，321/388例为无精子症(82.7%)，54/130例为隐精(41.5%)。相比之下，75%的少精子症病例仍无法解释。无精症的主要原因是严重的性功能障碍(占71.7%)。无精子症占继发性性腺功能减退症的86.4%，占精道梗阻的97.1%。在已知遗传因素的患者中，87.4%患有极端不孕症(无精子症、无精子症或无精子症)。泌尿生殖道先天畸形的发生率与精子产生受损的严重程度没有明显的相关性。之前定义的“潜在致病因素”精索静脉曲张和白细胞精子症被排除为男性不育的主要原因。然而，在特发性不孕症组中，他们的发病率是对照组的2倍(31.0vs13.5%和16.1vs7.4%；P<0.001)。此外，在几乎所有的患者亚组中，超重(或肥胖)患者和患有慢性病的患者的比例都显著增加。这项研究只包括精子总数减少的受试者。因此，这些发现不能自动适用于所有男性因素不育症病例。关于男性不育的绝对、致因和可能的因素，以及“潜在的致病因素”，在综合分析中取得的新见解和改进的清晰度，将是更新当前临床指南的宝贵工具。这项研究强调了知识差距，并重申迫切需要揭示少精子症病例背后的原因和机制以及可能的治疗方法，这些病例占特发性不育患者的大多数(86.3%)。该项目由欧盟通过ERDF项目快乐怀孕资助，编号3.2.0701.12-004(M.P.，M.L.)和爱沙尼亚研究理事会：拨款PUT181(M.P.)和IUT34-12(M.L.)。资助者没有参与研究设计、数据收集和分析、决定发表或准备手稿。我们没有相互竞争的利益需要申报。不适用
What are the primary causes of severe male factor infertility? Although 40% of all patients showed primary causes of infertility, which could be subdivided into three groups based on the severity of their effect, ~75% of oligozoospermia cases remained idiopathic. There are few large-scale epidemiological studies analyzing the causes of male factor infertility. A prospective clinical-epidemiological study was conducted at the Andrology Centre, Tartu University Hospital between 2005 and 2013, recruiting male partners of couples failing to conceive a child for over ≥12 months. Among 8518 patients, 1737 (20.4%) were diagnosed with severe male factor infertility. A reference group of fertile controls was comprised of 325 partners of pregnant women. The mean age of infertility patients and fertile controls was 33.2 ± 7.3 and 31.7 ± 6.3 years, respectively. All participants were examined using a standardized andrology workup, accompanied by a structured medical interview. Hormonal analysis included serum FSH, LH and testosterone. Semen quality was determined in accordance to the World Health Organization recommendations. Cases with spermatozoa concentrations of ≤5 million/ml were screened for chromosomal aberrations and Y-chromosomal microdeletions. The primary cause of infertility was defined for 695 of 1737 patients (~40%). The analyzed causal factors could be divided into absolute (secondary hypogonadism, genetic causes, seminal tract obstruction), severe (oncological diseases, severe sexual dysfunction) and plausible causal factors (congenital anomalies in uro-genital tract, acquired or secondary testicular damage). The latter were also detected for 11 (3.4%) men with proven fertility (diagnoses: unilateral cryptorchidism, testis cancer, orchitis, mumps orchitis). The causal factors behind the most severe forms of impaired spermatogenesis were relatively well understood; causes were assigned: for aspermia in 46/46 cases (100%), for azoospermia in 321/388 cases (82.7%), and for cryptozoospermia in 54/130 cases (41.5%). In contrast, 75% of oligozoospermia cases remained unexplained. The main cause of aspermia was severe sexual dysfunction (71.7% of aspermia patients). Azoospermia patients accounted for 86.4% of all cases diagnosed with secondary hypogonadism and 97.1% of patients with seminal tract obstruction. Of patients with a known genetic factor, 87.4% had extreme infertility (azoo-, crypto- or aspermia). The prevalence of congenital anomalies in the uro-genital tract was not clearly correlated with the severity of impaired sperm production. Previously defined ‘potential contributing factors’ varicocele and leukocytospermia were excluded as the primary causes of male infertility. However, their incidence was >2-fold higher (31.0 vs 13.5% and 16.1 vs 7.4%; P < 0.001) in the idiopathic infertility group compared to controls. In addition, the proportions of overweight (or obese) patients and patients suffering from a chronic disease were significantly increased in almost all of the patient subgroups. The study included only subjects with reduced total spermatozoa counts. Thus, these findings cannot be automatically applied to all male factor infertility cases. The novel insights and improved clarity achieved in the comprehensive analysis regarding the absolute, causative and plausible factors behind male infertility, as well as the ‘potential contributing factors’, will be valuable tools in updating the current clinical guidelines. The study highlights knowledge gaps and reiterates an urgent need to uncover the causes and mechanisms behind, and potential treatments of, oligozoospermic cases, representing the majority of idiopathic infertility patients (86.3%). The project was financed by the EU through the ERDF, project HAPPY PREGNANCY, no. 3.2.0701.12-004 (M.P., M.L.) and the Estonian Research Council: grants PUT181 (M.P.) and IUT34-12 (M.L.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. We have no competing interests to declare. Not applicable
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