补充叶酸和锌对不孕不育夫妇精液质量和婴儿活产的影响，这一成果由尤尼斯·肯尼迪·施赖弗国家儿童健康和人类发展研究所Sunni L. Mumford研究团队取得。研究论文于2020年1月7日发表在《美国医学会杂志》上。

市面上为提高男性生育力的膳食补充剂通常含有叶酸和锌，据说可提高精液质量。然而，还没有大规模试验来检验这种疗法对改善精液质量或婴儿活产的疗效。

为了探讨补充叶酸和锌对精液质量和婴儿活产的影响，2013年6月至2017年12月，研究组在美国4个生殖内分泌和不孕症治疗研究中心进行了一项多中心、随机、临床试验，共招募了2370对计划进行不孕症治疗的成年夫妇。研究组将男性按1：1随机分组，其中1185例每天服用5mg叶酸和30mg元素锌，1185例服用安慰剂，为期6个月。

2370名男性的平均年龄为33岁，其中有1773名（75%）接受了最终6个月的随访，1629名（69%）男性在治疗结束后提供了精液。叶酸+锌组的婴儿活产率为34%，安慰剂组为35%，差异不显著。

治疗6个月后，两组间的精子浓度、活力、形态、体积和活跃精子总数均无显著差异，但叶酸+锌组的精子DNA片段百分比为29.7%，显著高于安慰剂组（27.2%）。叶酸+锌组更容易发生胃肠道不良反应，其中腹部不适或疼痛的发生率为6%，恶心为4%，呕吐为3%；安慰剂组则分别为3%、2%和1%。

综上，对于不孕不育夫妇，与安慰剂相比，男性补充叶酸和锌并未显著改善精液质量或提高婴儿活产率。该发现不支持男性补充叶酸和锌来治疗不育症。

附：英文原文

Title: Effect of Folic Acid and Zinc Supplementation in Men on Semen Quality and Live Birth Among Couples Undergoing Infertility Treatment: A Randomized Clinical Trial

Author: Enrique F. Schisterman, Lindsey A. Sjaarda, Traci Clemons, Douglas T. Carrell, Neil J. Perkins, Erica Johnstone, Denise Lamb, Kayla Chaney, Bradley J. Van Voorhis, Ginny Ryan, Karen Summers, Jim Hotaling, Jared Robins, James L. Mills, Pauline Mendola, Zhen Chen, Elizabeth A. DeVilbiss, C. Matthew Peterson, Sunni L. Mumford

Issue&Volume: 2020/01/07

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.

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

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.

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.

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.

Results  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%]).

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.

DOI: 10.1001/jama.2019.18714

Source: https://jamanetwork.com/journals/jama/article-abstract/2758450