Division of Urology, Department of Surgery, University of Utah, Salt Lake City, UT, USA.
Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA.
Hum Reprod. 2021 Jul 19;36(8):2121-2133. doi: 10.1093/humrep/deab133.
What thresholds for total sperm count, sperm concentration, progressive motility, and total progressive motile sperm count (TPMC) are associated with earlier time-to-conception in couples undergoing fertility evaluation?
Values well above the World Health Organization (WHO) references for total sperm count, concentration, and progressive motility, and values up to 100 million for TPMC were consistently associated with earlier time-to-conception and higher conception rates.
Although individual semen parameters are generally not able to distinguish between fertile and infertile men, they can provide clinically useful information on time-to-pregnancy for counseling patients seeking fertility treatment. Compared to the conventional semen parameters, TPMC might be a better index for evaluating the severity of male infertility.
STUDY DESIGN, SIZE, DURATION: We used data from a longitudinal cohort study on subfertile men from 2002 to 2017 and included 6061 men with initial semen analysis (SA) in the study.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Men from subfertile couples who underwent a SA within the study period were included, and 5-year follow-up data were collected to capture conception data. Couples were further categorized into two subgroups: natural conception (n = 5126), after separating those who achieved conception using ART or IUI; natural conception without major female factor (n = 3753), after separating those with severe female factor infertility diagnoses. TPMC was calculated by multiplying the semen volume (ml) by sperm concentration (million/ml) and the percentage of progressively motile sperm (%). Cox proportional hazard models were used to report hazard ratios (HRs) with 95% CIs before and after adjusting for male age, the number of previous children before the first SA, and income. Using the regression tree method, we calculated thresholds for total sperm count, sperm concentration, progressive motility, and TPMC to best differentiate those who were more likely to conceive within 5 years after first SA from those less likely to conceive. We also plotted continuous values of semen parameters in predicting 5-year conception rates and time-to-conception.
Overall, the median time to conception was 22 months (95% CI: 21-23). A total of 3957 (65%) couples were known to have achieved conception within 5 years of the first SA. These patients were younger and had higher values of sperm concentration, progressive motility, and TPMC. In the overall cohort, a TPMC of 50 million best differentiated men who were more likely to father a child within 5 years. Partners of men with TPMC ≥50 million had a 45% greater chance of conception within 5 years in the adjusted model (HR: 1.45; 95% CI: 1.34-1.58) and achieved pregnancy earlier compared to those men with TPMC < 50 million (median 19 months (95% CI: 18-20) versus 36 months (95% CI: 32-41)). Similar results were observed in the natural conception cohort. For the natural conception cohort without major female factor, the TPMC cut-off was 20 million. In the visual assessment of the graphs for the continuous semen parameter values, 5-year conception rates and time-to-conception consistently plateaued at higher values of sperm concentration, total sperm count, progressive motility, and TPMC compared to the WHO reference levels and our calculated thresholds. For TPMC, values up to 100-150 million were still associated with a better conception rate and time-to-conception in the visual assessment of the curves.
LIMITATIONS, REASONS FOR CAUTION: There was limited information on female partners and potential for inaccuracies in capturing less severe female infertility diagnoses. Also we lacked details on assisted pregnancies achieved outside of our healthcare network (with possible miscoding as 'natural conception' in our cohort). We only used the initial SA and sperm morphology, another potentially important parameter, was not included in the analyses. We had no information on continuity of pregnancy attempts/intention, which could affect the time-to-conception data. Finally, most couples had been attempting conception for >12 months prior to initiating fertility treatment, so it is likely that we are underestimating time to conception. Importantly, our data might lack the generalizability to other populations.
Our results suggest that a TPMC threshold of 50 million sperm provided the best predictive power to estimate earlier time-to-conception in couples evaluated for male factor infertility. Higher values of sperm count, concentration and progressive motility beyond the WHO references were still associated with better conception rates and time-to-conception. This provides an opportunity to optimize semen parameters in those with semen values that are low but not abnormal according to the WHO reference values. These data can be used to better inform patients regarding their chances of conception per year when SA results are used for patient counseling.
STUDY FUNDING/COMPETING INTEREST(S): None.
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总精子数、精子浓度、前向运动精子比例和总前向运动精子计数（TPMC）的阈值与接受生育评估的夫妇中更早的受孕时间相关？
总精子数、浓度和前向运动精子比例的世界卫生组织（WHO）参考值高得多，以及 TPMC 值高达 1 亿，与更早的受孕时间和更高的受孕率相关。
尽管个体精液参数通常无法区分生育能力正常和生育能力异常的男性，但它们可以为寻求生育治疗的患者提供有关妊娠时间的有用临床信息。与传统精液参数相比，TPMC 可能是评估男性不育严重程度的更好指标。
研究设计、规模、持续时间：我们使用了 2002 年至 2017 年对亚生育男性进行的一项纵向队列研究的数据，该研究包括 6061 名在研究期间进行初始精液分析（SA）的男性。
参与者/材料、设置、方法：包括接受研究期间进行 SA 的亚生育夫妇的男性，收集了 5 年的随访数据以获取受孕数据。将夫妇进一步分为两个亚组：自然受孕（n=5126），将那些使用 ART 或 IUI 实现受孕的人分开；自然受孕且无主要女性因素（n=3753），将那些患有严重女性不孕诊断的人分开。通过将精液量（ml）乘以精子浓度（百万/ml）和前向运动精子的百分比（%）计算 TPMC。使用 Cox 比例风险模型报告风险比（HR），并在调整男性年龄、首次 SA 前的前几个孩子的数量和收入后进行。使用回归树方法，我们计算了总精子数、精子浓度、前向运动精子和 TPMC 的阈值，以最好地区分那些在首次 SA 后 5 年内更有可能受孕的人与那些不太可能受孕的人。我们还绘制了精液参数的连续值，以预测 5 年受孕率和受孕时间。
总的来说，中位受孕时间为 22 个月（95%CI：21-23）。共有 3957 对（65%）夫妇在首次 SA 后 5 年内已知已受孕。这些患者更年轻，精子浓度、前向运动精子和 TPMC 值更高。在整个队列中，TPMC 为 5000 万可最好地区分更有可能在 5 年内生育的男性。TPMC≥5000 万的男性伴侣在调整后的模型中（HR：1.45；95%CI：1.34-1.58），在 5 年内受孕的几率增加了 45%，与 TPMC<5000 万的男性相比，他们的受孕时间更早（中位数 19 个月（95%CI：18-20）与 36 个月（95%CI：32-41））。在自然受孕队列中也观察到了类似的结果。对于自然受孕且无主要女性因素的队列，TPMC 截止值为 2000 万。在连续精液参数值的图形视觉评估中，与 WHO 参考水平和我们计算的阈值相比，5 年受孕率和受孕时间在更高的精子浓度、总精子数、前向运动精子和 TPMC 值时趋于稳定。对于 TPMC，在曲线的视觉评估中，高达 100-1500 万的值仍与更好的受孕率和受孕时间相关。
局限性、谨慎原因：关于女性伴侣的信息有限，并且可能存在对不太严重的女性不孕诊断的准确性的潜在影响。我们还缺乏有关在我们的医疗保健网络之外获得的辅助妊娠的详细信息（在我们的队列中可能被错误编码为“自然受孕”）。我们只使用了初始 SA，并且精子形态学等另一个潜在的重要参数未包含在分析中。我们没有关于妊娠尝试/意图连续性的信息，这可能会影响受孕时间数据。最后，大多数夫妇在开始接受生育治疗之前已经尝试受孕超过 12 个月，因此我们可能低估了受孕时间。重要的是，我们的数据可能缺乏对其他人群的普遍性。
我们的结果表明，5000 万 TPMC 阈值提供了对男性因素不育评估夫妇更早的受孕时间的最佳预测能力。高于 WHO 参考值的精子计数、浓度和前向运动精子比例仍然与更好的受孕率和受孕时间相关。这为优化那些精液值较低但根据 WHO 参考值并非异常的精液参数提供了机会。这些数据可用于更好地告知患者，当使用 SA 结果进行患者咨询时，他们每年受孕的几率。
研究资金/利益冲突：无。
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