【探泌】为了怀孕，这些年没少吃……

作者：徐煜宇 2020-01-22 浏览 16

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研究表明，精子对氧化应激特别敏感，氧化应激可导致精子染色质损伤、细胞膜过氧化、运动能力受损和细胞凋亡增加。锌作为类固醇受体和参与DNA转录的金属酶的组成部分，在精子形成过程中有着重要作用。锌在精液中的浓度大约是血液中的30倍，这表明锌可能通过其抗氧化作用影响精液质量。叶酸能够为DNA合成和甲基化提供碳元素，其中甲基化在生成精子和清除自由基方面至关重要。此外，叶酸的适度利用和生物有效性还依赖于锌，二者具有协同作用。所以，在备孕时供男性使用的膳食补充剂通常都含有叶酸和锌。

虽然有证据表明，叶酸和锌的组合可能对男性生育力有帮助，但目前仍缺乏大规模临床试验的验证。对此，发表于《JAMA》杂志题为《Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial.》的文章有了新的结论。

【Abstract】

Importance: Dietary supplements marketed for male fertility commonly contain folic acid and zinc based on limited prior evidence for improving semen quality. However, no large-scale trial has examined the efficacy of this therapy for improving semen quality or live birth.

重要性：基于以往关于精液质量改善的有限证据，市面上用于提高男性生育力的膳食补充剂通常含有叶酸和锌。但是目前缺乏大规模试验来验证这种方法对改善精液质量和活产的疗效。

Objective: To determine the effect of daily folic acid and zinc supplementation on semen quality and live birth.

目的：研究每日补充叶酸和锌对精液质量和活产的影响。

Design,Setting,and Participants: The Folic Acid and Zinc Supplementation Trial was a multicenter randomized clinical trial. Couples (n = 2370; men aged ≥18 years and women aged 18-45 years) planning infertility treatment were enrolled at 4 US reproductive endocrinology and infertility care study centers between June 2013 and December 2017. The last 6-month study visit for semen collection occurred during August 2018, with chart abstraction of live birth and pregnancy information completed during April 2019.

设计、布置及参与者：该叶酸和锌补充试验是一项多中心随机临床试验。2013年6月至2017年12月，在美国4家生殖内分泌和不育症治疗研究中心招募计划治疗不育症的夫妻（n＝2370；男性≥18岁，女性18-45岁）。2018年8月进行最后一次取精。2019年4月完成活产和妊娠信息的图表提取。

Interventions: Men were block randomized by study center and planned infertility treatment (in vitro fertilization, other treatment at a study site, and other treatment at an outside clinic) to receive either 5 mg of folic acid and 30 mg of elemental zinc (n = 1185) or placebo (n = 1185) daily for 6 months.

干预措施：将男方随机分组按计划治疗不育症（体外受精、研究中心内的其他治疗以及门诊的其他治疗），并每日分别接受5mg叶酸和30mg锌（n＝1185），或安慰剂（n＝1185）持续6个月。

Main Outcomes and Measures: The co–primary outcomes were live birth (resulting from pregnancies occurring within 9 months of randomization) and semen quality parameters (sperm concentration, motility, morphology, volume, DNA fragmentation, and total motile sperm count) at 6 months after randomization.

主要观察指标：共同的主要观察指标为活产（源自9个月内出现妊娠）和6个月后的精液质量参数（精子浓度、活力、形态、体积、DNA碎片以及总运动精子数）。

Result: Among 2370 men who were randomized (mean age, 33 years), 1773 (75%) attended the final 6-month study visit. Live birth outcomes were available for all couples, and 1629 men (69%) had semen available for analysis at 6 months after randomization. Live birth was not significantly different between treatment groups (404 [34%] in the folic acid and zinc group and 416 [35%] in the placebo group; risk difference, −0.9% [95% CI, −4.7% to 2.8%]). Most of the semen quality parameters (sperm concentration, motility, morphology, volume, and total motile sperm count) were not significantly different between treatment groups at 6 months after randomization. A statistically significant increase in DNA fragmentation was observed with folic acid and zinc supplementation (mean of 29.7% for percentage of DNA fragmentation in the folic acid and zinc group and 27.2% in the placebo group; mean difference, 2.4% [95% CI, 0.5% to 4.4%]). Gastrointestinal symptoms were more common with folic acid and zinc supplementation compared with placebo (abdominal discomfort or pain: 66 [6%] vs 40 [3%], respectively; nausea: 50 [4%] vs 24 [2%]; and vomiting: 32 [3%] vs 17 [1%]).

结果：参与随机分组的2370名男性（平均年龄33岁），其中有1773名（75％）完成了最终6个月的研究随访。所有夫妻均提供了活产信息，并有1629名男性（69%）在6个月后进行了精液分析。治疗组之间的活产率没有显著差异（叶酸和锌组为404例 [34％]，安慰剂组为416例 [35％]；危险差为-0.9％[95％CI，-4.7％至2.8％ ]）。6个月后大多数精液质量参数（精子浓度、活力、形态、体积以及总运动精子数）在治疗组之间没有显著差异。DNA碎片在叶酸和锌组显著增加（DNA碎片平均百分比在叶酸和锌组与安慰剂组分别为29.7%和27.2%；平均差为2.4%[95%CI，0.5%-4.4%]）。叶酸和锌组比安慰剂组更容易出现消化道症状（腹部不适或疼痛为66例[6%] vs 40例[3%]，恶心为50例[4%] vs 24例[2%]，呕吐为32例[3%] vs 17例[1%]）。

Conclusions and relevance: Among a general population of couples seeking infertility treatment, the use of folic acid and zinc supplementation by male partners, compared with placebo, did not significantly improve semen quality or couples' live birth rates. These findings do not support the use of folic acid and zinc supplementation by male partners in the treatment of infertility.

结论与意义：在寻求治疗不育症的夫妻中，男方使用叶酸和锌补充剂（与安慰剂组相比）并不能显著改善精液质量和夫妻的活产率。该研究结果不支持男方使用叶酸和锌补充剂治疗不育症。

参考文献：

Schisterman EF, Sjaarda LA, Clemons T, et al. Effect of Folic Acid and Zinc Supplementation in Men>

编译|徐煜宇(广州医科大学附属第五医院)

编辑|榭小仙

审核|曹林

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