Jukic, A. M. Z., Baird, D. D., Weinberg, C. R., Wilcox, A. J., McConnaughey, D. R., & Steiner, A. Z. (2019). Pre-conception 25-hydroxyvitamin D (25(OH)D) and fecundability. Human Reproduction (Oxford, England), 34(11), 2163-2172. https://doi.org/10.1093/humrep/dez170
Jukic, A. M. Z., et al. "Pre-conception 25-hydroxyvitamin D (25(OH)D) and fecundability." Human Reproduction (Oxford, England), vol. 34, no. 11, 2019, pp. 2163-2172.
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Higher Vitamin D Levels May Be Linked to Faster Pregnancy
Women with the highest vitamin D levels had an estimated 35% higher chance of pregnancy each cycle than women with mid-range levels. The study tracked 522 women with no past infertility for up to a year. They kept daily and monthly diaries as they tried to get pregnant.
Key Findings
Among 522 women, 257 conceived during the study. Each step up in vitamin D level was tied to a slightly higher chance of pregnancy per cycle (ratio 1.10, 95% CI 0.96-1.25).
Women below the clinical threshold for vitamin D deficiency had an estimated 45% lower chance of pregnancy each cycle than women in the middle range (ratio 0.55, 95% CI 0.23-1.32).
Women with the highest vitamin D levels had an estimated 35% higher chance of pregnancy each cycle than women in the middle range (ratio 1.35, 95% CI 0.95-1.91).
The model put the chance of needing more than six cycles to conceive at 51% for the lowest group, 28% for the middle group and 15% for the highest group.
Dropping current smokers from the analysis, or adjusting for paternal age and weight, did not change the results; other checks gave similar results, ranging from slightly weaker to stronger.
Interpretation
The link was strongest among women with the highest and lowest vitamin D levels. The study followed 522 women in North Carolina with no infertility history for up to a year, using daily and monthly diaries. Vitamin D was measured once in blood at the start. The authors note that few cycles fell in the highest and lowest vitamin D groups. Earlier human and animal work also links vitamin D with fertility. The authors think fertility may improve at vitamin D levels above current guidelines. They call for more study of these higher levels and of how vitamin D may affect hormones, follicle growth, and the uterus lining.
RRM Context
Restorative reproductive medicine weighs health before a pregnancy. Vitamin D is one factor, along with weight and smoking. The study tracked ovulation with kits, body temperature, and cervical mucus. These are the same signs used in fertility awareness charting. Charting lets a woman and her doctor see her fertile days and weigh facts like vitamin D as part of a full checkup.
Our editorial summary of this paper, not the article's abstract.
Abstract
Study Question
Is pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study?
Summary Answer
There are suggestive associations of high 25(OH)D (at least 50 ng/ml) with increased fecundability and low 25(OH)D (<20 ng/ml) with reduced fecundability, but the estimates were imprecise.
What Is Known Already
Vitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist.
Study Design, Size, Duration
This community-based prospective cohort study included 522 women attempting to become pregnant between 2010 and 2016. The women completed online daily and monthly diaries until a positive home pregnancy test was observed or 12 months had elapsed.
Participants/Materials, Setting, Methods
The study included women from central North Carolina who were aged 30-44 with no history of infertility, with no more than 3 months of attempt time at recruitment. Women recorded vaginal bleeding so that the ongoing number of attempt cycles could be counted and used to quantify a woman's pregnancy attempt time. Blood collected at the study entry was analysed for 25(OH)D using liquid chromatography tandem mass spectrometry. Associations with fecundability were estimated with a log-binomial discrete time-to-event model.
Main Results and the Role of Chance
Among 522 women, 257 conceived during the study. The mean age was 33 years and the mean 25(OH)D was 36 ng/ml. There was an estimated 10% higher fecundability with each 10 ng/ml increase in 25(OH)D (fecundability ratio (FR) 1.10, 95% CI: 0.96, 1.25). The suggestive dose-response association with the continuous measure of 25(OH)D was driven by women in the lowest and the highest categories of 25(OH)D. Compared to women with 25(OH)D of 30-40 ng/ml, women below 20 ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50 ng/ml had an estimated 35% increase in fecundability (FR (CI): 1.35 (0.95, 1.91)). Across these three categories (25(OH)D of <20 ng/ml, 30-40 ng/ml and > 50 ng/ml), the probability of taking longer than 6 months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%).
Limitations, Reasons for Caution
While the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N = 107) or low 25(OH)D (N = 56) was small.
Wider Implications of the Findings
Our findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20 ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50 ng/ml).
Study Funding/Competing Interests
This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health (NIH) under award numbers R00HD079659 and R01HD067683 and supported in part by the Intramural Research Program of the National Institute of Environmental Health Sciences, under projects ES103086, ES049003 and ES044003. ClearBlue ovulation predictor kits were generously donated to AMZJ and AJW by Swiss Precision Diagnostics. Drs Wilcox and Jukic report non-financial support from Swiss Precision Diagnostics during the conduct of the study; Dr Jukic reports non-financial support from Theralogix, LLC, outside the submitted work. Otherwise there are no competing interests.
