To evaluate associations between preconception 25-hydroxyvitamin D (25(OH)D) levels and biomarkers in female and male partners on live birth (LB), pregnancy loss, and semen quality. Secondary analysis using the folic acid and zinc supplementation trial of couples seeking infertility treatment at four US centers (2013–2017). A target trial emulation framework was applied to estimate associations. Couples were observed for 9 months or through pregnancy. Clinics that provide reproductive endocrinology and infertility care in the US. Couples seeking infertility treatment. Preconception concentrations of 25(OH)D (primary) and associated biomarkers: vitamin D binding protein, calcium, free vitamin D, bioavailable vitamin D. Live birth and pregnancy loss were ascertained via self-report and medical records. Semen quality was ascertained 6 months after enrollment. Log-binomial regression estimated risk ratios and 95% confidence intervals (CIs). Individual and joint models and effect measure modification by preconception body mass index were considered. Among 2,370 couples, 19.5% of females and 29.9% of males were 25(OH)D deficient. Females with sufficient status had a 28%-higher likelihood of LB than deficient females (95% CI, 1.05–1.56). Female and male 25(OH)D status were associated with LB among those with normal body mass index (sufficient vs. deficient: female adjusted risk ratio [aRR], 1.39; 95% CI, 1.00–1.99; male aRR, 1.51; 95% CI, 1.01–2.25) and among obese female partners (sufficient vs. deficient: aRR, 1.33; 95% CI, 0.95–1.85). Couples whose both partners had higher 25(OH)D status had increased likelihood of LB (both not deficient vs. both deficient aRR, 1.26; 95% CI, 1.00–1.58). No associations were observed with pregnancy loss or semen quality. Similar results were found for all biomarkers except calcium. Preconception vitamin D status and bioavailability impact fertility among couples seeking infertility therapy, likely unrelated to semen quality. Body mass index stratified analyses demonstrated heterogeneous associations. NCT01857310.

中文翻译：

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孕前血清维生素 D 状态对生育结果的目标试验模拟：基于夫妇的方法


旨在评估女性和男性伴侣孕前 25-羟基维生素 D (25(OH)D) 水平与活产 (LB)、妊娠丢失和精液质量生物标志物之间的关联。对美国四个中心寻求不孕不育治疗的夫妇进行的叶酸和锌补充剂试验进行二次分析（2013-2017 年）。应用目标试验仿真框架来估计关联。对夫妇进行为期 9 个月或整个怀孕期间的观察。在美国提供生殖内分泌学和不孕不育护理的诊所。寻求不孕症治疗的夫妇。 25(OH)D（主要）和相关生物标志物的孕前浓度：维生素 D 结合蛋白、钙、游离维生素 D、生物可利用维生素 D。通过自我报告和医疗记录确定活产和妊娠损失。入组后 6 个月确定精液质量。对数二项式回归估计风险比和 95% 置信区间 (CI)。考虑了个体和联合模型以及通过孕前体重指数修改效果测量。在 2,370 对夫妇中，19.5% 的女性和 29.9% 的男性缺乏 25(OH)D。具有足够地位的女性患 LB 的可能性比缺乏地位的女性高 28%（95% CI，1.05-1.56）。在体重指数正常的人群中，女性和男性 25(OH)D 状态与 LB 相关（充足与不足：女性调整风险比 [aRR]，1.39；95% CI，1.00–1.99；男性 aRR，1.51；95） % CI，1.01–2.25）以及肥胖女性伴侣（充足与不足：aRR，1.33；95% CI，0.95–1.85）。伴侣双方 25(OH)D 状态较高的夫妇患 LB 的可能性增加（均未缺乏与均缺乏 aRR，1.26；95% CI，1.00–1.58）。没有观察到与妊娠丢失或精液质量之间的关联。 除钙以外的所有生物标志物都发现了类似的结果。孕前维生素 D 状态和生物利用度会影响寻求不孕症治疗的夫妇的生育能力，但可能与精液质量无关。体重指数分层分析表明存在异质关联。 NCT01857310。