Is There a Relevant Clinical Impact in Differentiating Idiopathic versus Unexplained Male Infertility?

Purpose: Overall, male factor infertility (MFI) accounts for up to 50% of etiologies of couple’s infertility, with almost 30% of MFI cases being idiopathic in nature. Idiopathic MFI does not support a tailored treatment work-up in clinical practice. To investigate
rates of and characteristics of men presenting for idiopathic versus unexplained primary infertility as compared with same-ethnicity, age-comparable fertile men.
Materials and Methods: Demographic, clinical and laboratory data from 3,098 primary infertile men consecutively evaluated were analyzed and compared with those of 103 fertile controls. Idiopathic male infertility (IMI) was defined for abnormality
at semen analysis with no previous history of diseases affecting fertility and normal findings on physical examination and genetic and laboratory testing. Unexplained male infertility (UMI) was defined as infertility of unknown origin with completely
normal findings at semen analysis. Descriptive statistics and logistic regression models tested the association between clinical variables and idiopathic infertility status.
Results: Overall, 570 (18.5%) and 154 (5.0%) patients depicted criteria suggestive for either IMI or UMI, respectively. Groups were similar in terms of age, BMI, CCI, recreational habits, hormonal milieu, and sperm DNA fragmentation indexes. Conversely, testicular volume was lower in IMI (p<0.001). Vitamin D3 levels were lower in IMI vs. UMI vs. fertile controls (p=0.01).
At multivariable logistic regression analysis only vitamin D3 deficiency (OR, 9.67; p=0.03) was associated with IMI. Characteristics suggestive for IMI versus UMI were observed in almost 20% and 5% of men, respectively. Overall, clinical differences
between groups were slightly significant and certainly not supportive of a tailored management work-up.
Conclusions: Current findings further support the urgent need of a more detailed and comprehensive assessment of infertile men to better tailoring their management work-up in the everyday clinical setting.

目的：总体而言，男性因素不育（male factor infertility, MFI）占夫妇不育病因的比例高达50%，其中近30%的MFI病例为特发性。特发性MFI在临床实践中无法支持个性化治疗方案的制定。本研究旨在调查特发性与不明原因原发性不育男性的比例及特征，并与同种族、年龄匹配的可育男性进行对比。
材料与方法：分析3098名连续评估的原发性不育男性的人口学、临床及实验室数据，并与103名可育对照组进行比较。特发性男性不育（idiopathic male infertility, IMI）定义为精液分析异常，但无既往影响生育的疾病史，且体格检查、遗传及实验室检测结果正常；不明原因男性不育（unexplained male infertility, UMI）定义为来源不明的不育，且精液分析结果完全正常。采用描述性统计和逻辑回归模型检验临床变量与特发性不育状态的关联。
结果：共570例（18.5%）和154例（5.0%）患者分别符合IMI或UMI的诊断标准。各组在年龄、体重指数（BMI）、CCI、娱乐习惯、激素环境及精子DNA碎片指数方面相似；但IMI组睾丸体积更低（p<0.001），维生素D3水平低于UMI组及可育对照组（p=0.01）。多变量逻辑回归分析显示，仅维生素D3缺乏（比值比OR=9.67；p=0.03）与IMI相关。近20%和5%的男性分别表现出IMI和UMI的特征。各组间临床差异轻微显著，显然无法支持个性化管理方案的制定。
结论：本研究结果进一步表明，在日常临床实践中迫切需要对不育男性进行更详细、全面的评估，以更好地定制其管理方案。