Insights from a Pseudo-Polygyny Cohort unmasking high sperm concentration and low forward motility as potential risk factors for recurrent failure of sperm donation IVF (RFDI), a subset of unexplained male infertility (UMI).

IF 10.8 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
EBioMedicine Pub Date : 2025-09-01 Epub Date: 2025-08-05 DOI:10.1016/j.ebiom.2025.105871
Tiancheng Zhang, Fan Dong, Xu Zhang, Ping Ping, Jin Qiu, Zhen Lu, Huachun Zou, Qian Xiao, Jianhui Li, Gaoyue Zhang, Huijuan Shi, Xiangfeng Chen
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引用次数: 0

Abstract

Background: Unexplained male infertility (UMI) accounts for 15%-30% of cases of male infertility, but it is poorly understood. We investigated potential risk factors for UMI leveraging data from a sperm bank with a "one male to multiple females" structure to reduce confounding arising from female factors.

Methods: Data on sperm donation provided by the Shanghai Human Sperm Bank (SHSB) to 39 qualified reproduction centres across China, along with information on IVF (In Vitro Fertilization) donor insemination cycles (DICs) performed at these centres and their reported outcomes, were retrieved from the Shanghai Human Sperm Bank (SHSB) for the period from 2004 to 2018. The association between semen parameters, demographic factors, and Cumulative Live Birth Rate from Donor Insemination (cLBR -DI) was analysed using linear regression analysis. Recurrent Failure of Sperm Donation IVF (RFDI) was defined as ≤1 pregnancy despite ≥4 DICs (indicating a cLBR -DI of ≤25%). Progressive Motility Rate (PR) refers to the percentage of grade (a + b) sperm among all sperm ((a + b)/(a + b + c + d)%). Forward Motility Rate (FR) refers to the percentage of grade (a + b) sperm among (a + b + c) sperm ((a + b)/(a + b + c)%). Sperm concentration<100 × 106/mL and FR > 95% was termed as normal group. The group with sperm concentration>200 × 106/mL or FR < 90% was termed high-risk RFDI (HR-RFDI). Logistic regression was used to assess correlations of RFDI. Propensity score matching (PSM) was used to match the RFDI and non-RFDI populations. Miscarriage conditions were also analysed in this study.

Findings: We included 4734 qualifying sperm donors and 17,307 IVF DICs, of which 2447 donors had more than 4 DICs per donor, forming a Pseudo-Polygyny Cohort. 8.05% of the 2447 donors with normal semen parameters and more than 4 DICs met RFDI criteria. RFDI donors exhibited higher sperm concentration (96.00 [75.00, 130.00] vs. 90.00 [72.00, 122.22], p = 0.057) and lower Forward Motility Rate (95.12 [89.02, 97.01] vs. 96.59 [93.33, 97.30], p < 0.001) compared to non-RFDI. Forward Motility Rate, rather than Progressive Motility Rate, correlated with cLBR -DI Compared to the normal group, HR-RFDI had an over three-fold higher risk of RFDI before (RR = 3.48, 95% CI [1.94, 6.25], p < 0.0001) and after (OR = 3.04, 95% CI [1.92, 4.81], p < 0.0001) PSM adjustment. Notably, RFDI donors had higher miscarriage rates (10.80 ± 14.20% vs. 3.90 ± 8.50%, p < 0.0001) compared to non-RFDI donors. High-risk RFDI donors also had higher miscarriage rates (5.40 ± 9.20% vs. 4.20 ± 9.40%, p = 0.011) compared to low-risk RFDI donors.

Interpretation: The negative impact of high sperm concentration on pseudo-polygyny cohort in vitro fertilization (IVF) outcomes strongly supports the hypothesis of a potential "inverted U-shape" relationship between sperm concentration and fertility. The superior correlation of FR with sperm donation IVF outcomes compared to PR suggests that FR may be a more meaningful measure of sperm motility in this context. The identification of an RFDI population, characterized by recurrent IVF failure and high miscarriage rates despite normal semen parameters, provides substantial evidence that the prevalence and severity of unexplained male infertility (UMI) may be greater than currently recognized. Therefore, a more comprehensive evaluation of male fertility should be considered in couples experiencing these issues.

Funding: National Key R&D Program of China (2023YFC2705503), Fujian Province's Third Batch of Flexible Introduction of High-Level Medical Talent Teams (TD202307) and the National Key Technologies R&D Program (2023YFC2306700).

一项伪一夫多妻队列研究揭示了高精子浓度和低前向运动是精子捐赠IVF (RFDI)复发性失败的潜在危险因素,这是不明原因男性不育(UMI)的一个子集。
背景:不明原因男性不育症(UMI)占男性不育症病例的15%-30%,但对其了解甚少。我们利用“一男多女”结构的精子库数据调查了UMI的潜在危险因素,以减少女性因素引起的混淆。方法:从上海人类精子库(SHSB)检索2004年至2018年期间上海人类精子库(SHSB)向全国39个合格生殖中心提供的精子捐赠数据,以及在这些中心进行的体外受精(IVF)供体授精周期(dic)及其报告结果的信息。采用线性回归分析精液参数、人口统计学因素与供体人工授精累积活产率(cLBR -DI)之间的关系。精子捐赠IVF (RFDI)的复发性失败定义为尽管DICs≥4(表明cLBR -DI≤25%),但仍≤1次妊娠。进行性活动力率(PR)是指(a + b)级精子占全部精子的百分比((a + b)/(a + b + c + d)%)。前向运动率(FR)指(a + b)级精子占(a + b + c)级精子的百分比((a + b)/(a + b + c)%)。精子浓度6/mL、FR bb0 95%为正常组。精子浓度低于200 × 106/mL或FR < 90%者称为高危RFDI (HR-RFDI)。采用Logistic回归评估RFDI的相关性。倾向得分匹配(PSM)用于匹配RFDI和非RFDI人群。本研究还分析了流产情况。结果:我们纳入了4734名符合条件的捐精者和17307名体外受精DICs,其中2447名捐精者每个DICs超过4个,形成伪一夫多妻队列。在2447名精液参数正常且DICs超过4个的捐精者中,8.05%符合RFDI标准。与非RFDI供者相比,RFDI供者精子浓度较高(96.00[75.00,130.00]比90.00 [72.00,122.22],p = 0.057),前向运动率较低(95.12[89.02,97.01]比96.59 [93.33,97.30],p < 0.001)。与正常组相比,调整PSM前(RR = 3.48, 95% CI [1.94, 6.25], p < 0.0001)和调整PSM后(OR = 3.04, 95% CI [1.92, 4.81], p < 0.0001), HR-RFDI发生的风险高出3倍以上。值得注意的是,与非RFDI供者相比,RFDI供者的流产率更高(10.80±14.20% vs. 3.90±8.50%,p < 0.0001)。高风险RFDI供者的流产率也高于低风险RFDI供者(5.40±9.20% vs 4.20±9.40%,p = 0.011)。解释:高精子浓度对假一夫多妻队列体外受精(IVF)结果的负面影响有力地支持了精子浓度与生育能力之间潜在的“倒u型”关系的假设。与PR相比,FR与精子捐赠IVF结果的相关性更强,这表明FR可能是在这种情况下更有意义的精子活力指标。尽管精液参数正常,但RFDI人群的特征是IVF反复失败和高流产率,这为不明原因男性不育症(UMI)的患病率和严重程度可能比目前认识到的要高提供了大量证据。因此,在遇到这些问题的夫妇中,应该考虑对男性生育能力进行更全面的评估。资助项目:国家重点研发计划项目(2023YFC2705503)、福建省第三批灵活引进高层次医学人才队伍项目(TD202307)、国家重点技术研发计划项目(2023YFC2306700)。
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来源期刊
EBioMedicine
EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍: eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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