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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.
Fertility and Sterility
|October 6, 2025
Summary
The vitamin D binding protein (DBP) Gc1f haplotype is linked to higher live birth rates and lower early pregnancy loss in women undergoing ovarian stimulation. This suggests DBP
Area of Science:
- Reproductive Endocrinology
- Genetics and Genomics
- Endocrinology
Background:
- The role of vitamin D binding protein (DBP) in reproductive outcomes is poorly understood.
- Existing research often assumes DBP's effects are solely due to vitamin D bioavailability, overlooking its independent functions.
- Polycystic ovary syndrome (PCOS) and unexplained infertility are common causes of female infertility.
Purpose of the Study:
- To investigate the association between DBP concentration and haplotypes (Gc1f, Gc1s, Gc2) with reproductive outcomes.
- To evaluate these associations in patients with PCOS or unexplained infertility undergoing ovarian stimulation.
- To explore potential vitamin D-independent mechanisms of DBP action in reproduction.
Main Methods:
- Retrospective cohort study analyzing data from two randomized controlled trials: Pregnancy in Polycystic Ovary Syndrome II and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation.
- Included 881 participants: 376 with PCOS and 505 with unexplained infertility.
- Assessed DBP concentration and DBP Gc1f, Gc1s, and Gc2 haplotypes as exposures, with live birth, early pregnancy loss, and obstetric complications as outcomes.
Main Results:
- No significant association was found between DBP concentration, Gc1s, or Gc2 haplotypes and live birth rates.
- The Gc1f haplotype showed a significant association with increased odds of live birth (aOR, 1.49) and decreased odds of early pregnancy loss (aOR, 0.46) after adjusting for confounders.
- No association was observed between the Gc1f haplotype and obstetric complications.
Conclusions:
- The DBP Gc1f haplotype is independently associated with improved live birth rates and reduced early pregnancy loss in women undergoing ovarian stimulation.
- These findings challenge the 'free hormone theory,' suggesting vitamin D-independent mechanisms for DBP's role in reproductive success.
- Further research is warranted to elucidate the specific non-vitamin D-related pathways through which DBP influences reproductive outcomes.
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