DiTosto Julia D, Caniglia Ellen C, Hinkle Stefanie N, Sealy Naria, Schisterman Enrique F, Johnstone Erica, Mendola Pauline, Mills James, Hotaling Jim, Ryan Ginny, Mumford Sunni L
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Obstetrics and Gynecology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Fertil Steril. 2025 Feb;123(2):300-312. doi: 10.1016/j.fertnstert.2024.08.332. Epub 2024 Aug 20.
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.
Couples seeking infertility treatment.
INTERVENTION(S): Preconception concentrations of 25(OH)D (primary) and associated biomarkers: vitamin D binding protein, calcium, free vitamin D, bioavailable vitamin D.
MAIN OUTCOME MEASURE(S): 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.
RESULT(S): 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.
CONCLUSION(S): 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.
评估孕前25-羟维生素D（25(OH)D）水平与男女伴侣体内生物标志物在活产（LB）、妊娠丢失和精液质量方面的关联。
对在美国四个中心寻求不孕治疗的夫妇进行的叶酸和锌补充试验进行二次分析（2013 - 2017年）。应用目标试验模拟框架来估计关联。对夫妇观察9个月或直至妊娠结束。
寻求不孕治疗的夫妇。
孕前25(OH)D浓度（主要指标）及相关生物标志物：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丢失情况。入组6个月后确定精液质量。对数二项回归估计风险比和95%置信区间（CIs）。考虑了个体模型和联合模型以及孕前体重指数对效应测量的修正。
在2370对夫妇中，19.5%的女性和29.9%的男性存在25(OH)D缺乏。25(OH)D水平充足的女性活产的可能性比缺乏的女性高28%（95%CI，1.05 - 1.56）。在体重指数正常的夫妇中（充足与缺乏相比：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）以及肥胖女性伴侣中（充足与缺乏相比：aRR，1.33；95%CI，0.95 - 1.85），男女25(OH)D水平与活产相关。双方25(OH)D水平较高的夫妇活产的可能性增加（双方均不缺乏与双方均缺乏相比aRR，1.26；95%CI，1.00 - 1.58）。未观察到与妊娠丢失或精液质量的关联。除钙外，所有生物标志物均得到类似结果。
孕前维生素D状态和生物可利用性会影响寻求不孕治疗夫妇的生育能力，可能与精液质量无关。体重指数分层分析显示了异质性关联。
NCT01857310。
