Pre-conception 25-hydroxyvitamin D (25(OH)D) and fecundability.

Abstract

STUDY QUESTION\nIs pre-conception 25(OH)D associated with the per cycle probability of conception, i.e fecundability, in a prospective cohort study?\n\n\nSUMMARY ANSWER\nThere are suggestive associations of high 25(OH)D (at least 50\xa0ng/ml) with increased fecundability and low 25(OH)D (<20\xa0ng/ml) with reduced fecundability, but the estimates were imprecise.\n\n\nWHAT IS KNOWN ALREADY\nVitamin D has been associated with reproductive function and fertility in animal studies, but few human studies exist.\n\n\nSTUDY DESIGN, SIZE, DURATION\nThis 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\xa0months had elapsed.\n\n\nPARTICIPANTS/MATERIALS, SETTING, METHODS\nThe 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.\n\n\nMAIN RESULTS AND THE ROLE OF CHANCE\nAmong 522 women, 257 conceived during the study. The mean age was 33\xa0years and the mean 25(OH)D was 36\xa0ng/ml. There was an estimated 10% higher fecundability with each 10\xa0ng/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\xa0ng/ml, women below 20\xa0ng/ml had an estimated 45% reduction in fecundability (FR (CI): 0.55 (0.23, 1.32)), and women with at least 50\xa0ng/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\xa0ng/ml, 30-40\xa0ng/ml and\u2009>\u200950\xa0ng/ml), the probability of taking longer than 6\xa0months to conceive was, respectively, 51% (17%, 74%), 28% (17%, 39%) and 15% (10%, 37%).\n\n\nLIMITATIONS, REASONS FOR CAUTION\nWhile the distribution of 25(OH)D was wide, the number of observed cycles with high 25(OH)D (N\u2009=\u2009107) or low 25(OH)D (N\u2009=\u200956) was small.\n\n\nWIDER IMPLICATIONS OF THE FINDINGS\nOur findings are consistent with prior reports of reduced fertility in women with 25(OH)D concentrations below the clinically defined deficiency level (20\xa0ng/ml). Further studies are needed to evaluate the possible reproductive benefits of considerably higher 25(OH)D concentration (>50\xa0ng/ml).\n\n\nSTUDY FUNDING/COMPETING INTEREST(S)\nThis 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.\n\n\nTRIAL REGISTRATION NUMBER\nN/A.