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Published on: January 28, 2013
Vitamin D binding protein and reproductive outcomes
Iris Tien-Lynn Lee1, Andrew N Hoofnagle2, Richard S Legro3
1Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PennCsylvania.
Objective:
Little is known about whether vitamin D binding protein (DBP) plays a role in reproductive outcomes. The few existing studies have largely presumed that any effects of DBP are due to its modulation of vitamin D bioavailability per the "free hormone theory" despite its many vitamin D-independent functions. This study, therefore, aimed to comprehensively evaluate the association between DBP concentration/haplotype and reproductive outcomes in patients with polycystic ovary syndrome or unexplained infertility undergoing ovarian stimulation.
Design:
Retrospective cohort study, secondary analysis of randomized controlled trials Pregnancy in Polycystic Ovary Syndrome II and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation.
Subjects:
376 participants with polycystic ovary syndrome (Pregnancy in Polycystic Ovary Syndrome II), 505 participants with unexplained infertility (Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation).
Exposure:
Vitamin D binding protein concentration and DBP Gc1f, Gc1s, and Gc2 haplotypes.
Main Outcome Measures:
Primary: live birth. Secondary: early pregnancy loss and composite of preterm delivery, preeclampsia, and fetal growth restriction.
Results:
A total of 881 participants were included. There was no association between DBP concentration, Gc1s, or Gc2 and live birth. When adjusting for age, race, body mass index, 25-hydroxyvitamin D concentration, and treatment arm, the Gc1f haplotype was associated with increased odds of live birth (adjusted odds ratio [aOR], 1.49; 95% confidence interval [CI], 1.06-2.09) and decreased odds of early pregnancy loss (aOR, 0.46; 95% CI, 0.25-0.86). There was no association with obstetric complications (aOR, 0.76; 95% CI, 0.39-1.47).
Conclusion:
The Gc1f haplotype of DBP was associated with increased odds of live birth and decreased odds of early pregnancy loss independent of 25-hydroxyvitamin D and DBP concentration. Because Gc1f results in the DBP variant with the greatest binding affinity for vitamin D, these findings challenge the current narrative that associations between DBP and reproductive outcomes are primarily due to modulation of vitamin D bioavailability. Additional studies are needed to investigate other mechanisms for the role of DBP in reproductive outcomes.
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