Samantha F Butts1, David B Seifer2, Nathanael Koelper1, Suneeta Senapati1, Mary D Sammel3, Andrew N Hoofnagle4, Andrea Kelly5, Steven A Krawetz6,7, Nanette Santoro8, Heping Zhang9, Michael P Diamond10, Richard S Legro11. 1. Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 2. Department of Obstetrics, Gynecology and Reproductive Services, Yale University School of Medicine, New Haven, Connecticut. 3. Center for Clinical Epidemiology and Biostatics, Perelman School of Medicine, University of Pennsylvania, Pennsylvania. 4. Department of Laboratory Medicine, University of Washington, Seattle, Washington. 5. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan. 7. Fertility and Infertility Branch, Eunice Kenney Shriver National Institute of Child Health and Human Development, Rockville, Maryland. 8. Department of Obstetrics and Gynecology, University of Colorado, Aurora, Colorado. 9. Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut. 10. Department of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia. 11. Department of Obstetrics and Gynecology, Pennsylvania State University Hershey, Hershey, Pennsylvania.
Abstract
Context: The impact of vitamin D deficiency on the success of ovarian stimulation according to underlying infertility diagnosis has not been investigated. Objective: To evaluate the relationship between vitamin D deficiency and reproductive outcomes after ovarian stimulation in women with either polycystic ovary syndrome (PCOS) or unexplained infertility. Design: Retrospective cohort study. Setting: Analysis of randomized controlled trial (RCT) data. Participants: Participants from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) RCT (n = 607); participants from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) RCT of unexplained infertility (n = 647). Interventions: Serum 25(OH)D levels measured in banked sera. Main Outcome Measures: Primary: live birth; secondary: ovulation (PPCOS II), pregnancy, and early pregnancy loss. Results: In PPCOS II, subjects with vitamin D deficiency [25(OH)D < 20 ng/mL or 50 nmol/L] were less likely to ovulate (adjusted OR, 0.82; 95% CI, 0.68 to 0.99; P = 0.04) and experienced a 40% lower chance of live birth (adjusted OR, 0.63; 95% CI, 0.41 to 0.98; P = 0.04) than those not deficient. In AMIGOS, no significant association between vitamin D deficiency and live birth was noted. In pregnant subjects from both studies, vitamin D deficiency was associated with elevated risk of early pregnancy loss (OR, 1.6; 95% CI, 1.0 to 2.6; P = 0.05). Conclusions: In this investigation of women pursuing ovarian stimulation, the association between vitamin D deficiency and diminished live birth relied on carrying the diagnosis of PCOS and was not observed in unexplained infertility. Given the generally modest success of ovarian stimulation, addressing vitamin D deficiency may prove an important treatment adjunct for many infertile women.
Context: The impact of vitamin Ddeficiency on the success of ovarian stimulation according to underlying infertility diagnosis has not been investigated. Objective: To evaluate the relationship between vitamin Ddeficiency and reproductive outcomes after ovarian stimulation in women with either polycystic ovary syndrome (PCOS) or unexplained infertility. Design: Retrospective cohort study. Setting: Analysis of randomized controlled trial (RCT) data. Participants: Participants from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) RCT (n = 607); participants from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) RCT of unexplained infertility (n = 647). Interventions: Serum 25(OH)D levels measured in banked sera. Main Outcome Measures: Primary: live birth; secondary: ovulation (PPCOS II), pregnancy, and early pregnancy loss. Results: In PPCOS II, subjects with vitamin Ddeficiency [25(OH)D < 20 ng/mL or 50 nmol/L] were less likely to ovulate (adjusted OR, 0.82; 95% CI, 0.68 to 0.99; P = 0.04) and experienced a 40% lower chance of live birth (adjusted OR, 0.63; 95% CI, 0.41 to 0.98; P = 0.04) than those not deficient. In AMIGOS, no significant association between vitamin Ddeficiency and live birth was noted. In pregnant subjects from both studies, vitamin Ddeficiency was associated with elevated risk of early pregnancy loss (OR, 1.6; 95% CI, 1.0 to 2.6; P = 0.05). Conclusions: In this investigation of women pursuing ovarian stimulation, the association between vitamin Ddeficiency and diminished live birth relied on carrying the diagnosis of PCOS and was not observed in unexplained infertility. Given the generally modest success of ovarian stimulation, addressing vitamin Ddeficiency may prove an important treatment adjunct for many infertile women.
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